Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders

Abstract

Berberine-containing plants have been traditionally used in different parts of the world for the treatment of inflammatory disorders, skin diseases, wound healing, reducing fevers, affections of eyes, treatment of tumors, digestive and respiratory diseases, and microbial pathologies. The physico-chemical properties of berberine contribute to the high diversity of extraction and detection methods. Considering its particularities this review describes various methods mentioned in the literature so far with reference to the most important factors influencing berberine extraction. Further, the common separation and detection methods like thin layer chromatography, high performance liquid chromatography, and mass spectrometry are discussed in order to give a complex overview of the existing methods. Additionally, many clinical and experimental studies suggest that berberine has several pharmacological properties, such as immunomodulatory, antioxidative, cardioprotective, hepatoprotective, and renoprotective effects. This review summarizes the main information about botanical occurrence, traditional uses, extraction methods, and pharmacological effects of berberine and berberine-containing plants.

Introduction

Berberine

Berberine(5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a] quinolizinium) Figure 1, is a nonbasic and quaternary benzylisoquinoline alkaloid, a relevant molecule in pharmacology and medicinal chemistry. Indeed, it is known as a very important natural alkaloid for the synthesis of several bioactive derivatives by means of condensation, modification, and substitution of functional groups in strategic positions for the design of new, selective, and powerful drugs (Chen et al., 2005).

Figure 1

Traditional use of berberine-containing species

In the Berberidaceae family, the genus Berberis comprises of ~450–500 species, which represent the main natural source of berberine. Plants of this genus are used against inflammation, infectious diseases, diabetes, constipation, and other pathologies (Singh A. et al., 2010). The oldest evidence of using barberry fruit (Berberis vulgaris) as a blood purifying agent was written on the clay tablets in the library of Assyrian emperor Asurbanipal during 650 BC (Karimov, 1993). In Asia, the extensive use of the stem, stem bark, roots, and root bark of plants rich in berberine, particularly Berberis species, has more than 3000 years of history. Moreover, they have been used as raw material or as an important ingredient in Ayurvedic and traditional Chinese medicine (Birdsall, 1997; Kirtikar and Basu, 1998; Gupta and Tandon, 2004; Kulkarni and Dhir, 2010). In Ayurveda, Berberis species have been traditionally used for the treatment of a wide range of infections of the ear, eye, and mouth, for quick healing of wounds, curing hemorrhoids, indigestion and dysentery, or treatment of uterine and vaginal disorders. It has also been used to reduce obesity, and as an antidote for the treatment of scorpion sting or snakebite (Dev, 2006). Berberine extracts and decoctions are traditionally used for their activities against a variety of microorganisms including bacteria, viruses, fungi, protozoa, helminthes, in Ayurvedic, Chinese, and Middle-Eastern folk medicines (Tang et al., 2009; Gu et al., 2010).

In Yunani medicine, Berberis asiatica has multiple uses, such as for the treatment of asthma, eye sores, jaundice, skin pigmentation, and toothache, as well as for favoring the elimination of inflammation and swelling, and for drying ulcers (Kirtikar and Basu, 1998). Decoction of the roots, and stem barks originating from Berberis aristata, B. chitria, and B. lycium (Indian Berberis species), have been used as domestic treatment of conjunctivitis or other ophthalmic diseases, enlarged liver and spleen, hemorrhages, jaundice, and skin diseases like ulcers (Rajasekaran and Kumar, 2009). On the other hand, the use of decoction of Indian barberry mixed with honey has also been reported for the treatment of jaundice. Additionally, it has been reported the use of decoction of Indian barberry and Emblic myrobalan mixed with honey in the cure of urinary disorders as painful micturition (Kirtikar and Basu, 1998). Numerous studies dealing with its antimicrobial and antiprotozoal activities against different types of infectious organisms (Vennerstrom et al., 1990; Stermitz et al., 2000; Bahar et al., 2011) have been assessed so far. Moreover, it has been used to treat diarrhea (Chen et al., 2014) and intestinal parasites since ancient times in China (Singh and Mahajan, 2013), and the Eastern hemisphere, while in China it is also used for treating diabetes (Li et al., 2004).

Nowadays, a significant number of dietary supplements based on plants containing berberine (Kataoka et al., 2008) are used for reducing fever, common cold, respiratory infections, and influenza (Fabricant and Farnsworth, 2001). Another reported use for berberine-containing plants is their application as an astringent agent to lower the tone of the skin. Also, positive effects were observed on the mucous membranes of the upper respiratory tract and gastrointestinal system with effects on the associated ailments (Chen et al., 2014; Yu et al., 2016).

In southern South America leaves and bark of species of the genus Berberis are used in traditional medicine administered for mountain sickness, infections, and fever (San Martín, 1983; Houghton and Manby, 1985; Anesini and Perez, 1993).

Furthermore, there are other genera which contain berberine. The genus Mahonia comprises of several species that contain berberine. Within them, M. aquifolium has been traditionally used for various skin conditions. Due to its main alkaloid (berberine), is known to be used in Asian medicine for its antimicrobial activity. Coptidis rhizoma (rhizomes of Coptis chinensis), another plant which contains berberine, is a famous herb very frequently used in traditional Chinese medicine for the elimination of toxins, “damp-heat syndromes”, “purge fire”, and to “clear heat in the liver” (Tang et al., 2009). Table 1 gathers a synthesis of the main traditional uses of species containing berberine.

Botanical sources of berberine

Berberine has been detected, isolated, and quantified from various plant families and genera including Annonaceae (Annickia, Coelocline, Rollinia, and Xylopia), Berberidaceae (Berberis, Caulophyllum, Jeffersonia, Mahonia, Nandina, and Sinopodophyllum), Menispermaceae (Tinospora), Papaveraceae (Argemone, Bocconia, Chelidonium, Corydalis, Eschscholzia, Glaucium, Hunnemannia, Macleaya, Papaver, and Sanguinaria), Ranunculaceae (Coptis, Hydrastis, and Xanthorhiza), and Rutaceae (Evodia, Phellodendron, and Zanthoxyllum) (Table 2). The genus Berberis is well-known as the most widely distributed natural source of berberine. The bark of B. vulgaris contains more than 8% of alkaloids, berberine being the major alkaloid (about 5%) (Arayne et al., 2007).

Berberine is also widely present in barks, leaves, twigs, rhizomes, roots, and stems of several medicinal plants species, including Argemone mexicana (Etminan et al., 2005), Berberis aristata, B. aquifolium, B. heterophylla, B. beaniana, Coscinium fenestratum (Rojsanga and Gritsanapan, 2005), C. chinensis, C. japonica, C. rhizome, Hydratis canadensis (Imanshahidi and Hosseinzadeh, 2008), Phellodendron amurense, P. chinense, Tinospora cordifolia (Khan et al., 2011), Xanthorhiza simplicissima (Bose et al., 1963; Knapp et al., 1967; Sato and Yamada, 1984; Steffens et al., 1985; Inbaraj et al., 2001; Liu et al., 2008a; Srinivasan et al., 2008; Vuddanda et al., 2010). Several researches found that berberine is widely distributed in the barks, roots, and stems of plants, nevertheless, bark and roots are richer in berberine compared to other plant parts (Andola et al., 2010a,b). In the Papaveraceae family, Chelidonium majus is another important herbal source of berberine (Tomè and Colombo, 1995). An important number of plants for medicinal use, such as Coptidis rhizoma and barberry, are the natural sources with the highest concentration of berberine. Barberries, such as Berberis aristata, B. aquifolium, B. asiatica, B. croatica, B. thunbergii, and B. vulgaris, are shrubs grown mainly in Asia and Europe, and their barks, fruits, leaves, and roots are often widely used as folk medicines (Imanshahidi and Hosseinzadeh, 2008; Kosalec et al., 2009; Andola et al., 2010c; Kulkarni and Dhir, 2010). Different research groups have reported that maximum berberine concentration accumulates in root (1.6–4.3%) and in most of the Berberis species, plants that grow at low altitude contain more berberine compared to higher altitude plants (Chandra and Purohit, 1980; Mikage and Mouri, 1999; Andola et al., 2010a). However, a correlation could not be established within the results of berberine concentration regarding to species and season of the year (Srivastava et al., 2006a,c; Andola et al., 2010c; Singh et al., 2012). Comparative studies of berberine concentration contained in different species of the same genus have been reported, e.g., higher berberine content in B. asiatica (4.3%) in comparison to B. lycium (4.0%), and B. aristata (3.8%). Meanwhile, Srivastava et al. (2004) documented a higher berberine content in root of B. aristata (2.8%) compared with B. asiatica (2.4%) (Andola et al., 2010a). Seasonal variation of berberine concentration has been reported, e.g., the maximum yield of berberine for B. pseudumbellata was obtained in the summer harvest, and was 2.8% in the roots and 1.8% for the stem bark, contrary to that reported in the roots of B. aristata, where the berberine concentration (1.9%) is higher for the winter harvest (Rashmi et al., 2009). These variations may be caused to multiple factors, among which stand out: (i) the intraspecific differences, (ii) location and/or, (iii) the analytical techniques used. Table 2 gathers a synthesis of the main species containing berberine.

Extraction methods

Berberine, a quaternary protoberberine alkaloid (QPA) is one of the most widely distributed alkaloid of its class. Current studies suggest that isolation of the QPA alkaloids from their matrix can be performed using several methods. The principles behind these methods consist of the interconversion reaction between the protoberberine salt and the base. The salts are soluble in water, stable in acidic, and neutral media, while the base is soluble in organic solvents. Thus during the extraction procedure, the protoberberine salts are converted in their specific bases and further extracted in the organic solvents (Marek et al., 2003; Grycová et al., 2007).

In the case of berberine, the classical extraction techniques like maceration, percolation, Soxhlet, cold or hot continuous extraction are using different solvent systems like methanol, ethanol, chloroform, aqueous, and/or acidified mixtures. Berberine's sensitivity to light and heat is the major challenge for its extraction. Hence, exposure to high temperature and light could lead to berberine degradation and thus influencing its matrix recovery. In his study Babu et al. (2012) demonstrated that temperature represent a crucial factor in both extraction and drying treatments prior extraction. The yield of berberine content in C. fenestratum stem tissue samples was higher in case of samples dried under the constant shade with 4.6% weight/weight (w/w) as compared to samples dried in oven at 65°C (1.32% w/w) or sun drying (3.21% w/w). As well hot extraction procedure with methanol or ethanol at 50°C gave lower extraction yields when compared with methanol or ethanol cold extraction at −20°C. Thus, berberine content in the shade-dried samples was 4.6% (w/w) for methanolic cold extraction and 1.29% (w/w) for methanolic hot extraction (Babu et al., 2012).

Along with extraction temperature, the choice of solvents is considered a critical step in berberine extraction as well (Figure 2). As seen in Table 3, methanol, ethanol, aqueous or acidified methanol or ethanol are the most used extraction solvents. The acidified solvents (usually with the addition of 0.5% of inorganic or organic acids) are used to combine with free base organic alkaloids and transform them in alkaloid salts with higher solubility (Teng and Choi, 2013). The effect of different inorganic acids like hydrochloric acid, phosphoric acid, nitric acid, and sulfuric acid as well as the effect of an organic acid like acetic acid were tested on berberine content and other alkaloids in rhizomes of Coptis chinensis Franch by Teng and Choi (2013). In this case, 0.34% phosphoric acid concentration was considered optimal. Moreover, when compared to other classical extraction techniques like reflux and Soxhlet extraction, the cold acid assisted extraction gave 1.1 times higher berberine yields.

Figure 2

Large solvent volumes and long extraction time represent other drawbacks of conventional extraction methods (Mokgadi et al., 2013). For example, Rojsanga and Gritsanapan (2005) used maceration process to extract 100 g of C. fenestratum plant material with a total volume of 3,200 mL solvent (80% ethanol) over a period of 416 h. Furthermore, in a different study, Rojsanga et al. (2006) used several classical extraction techniques like maceration, percolation, and Soxhlet extraction to extract the berberine from C. fenestratum stems. This time even if the extracted plant material was in a lower amount than the previous study (30 vs. 100 g), large solvent volumes (2,000 mL for maceration, 5,000 mL for percolation, and 600 mL for Soxhlet extraction) over long time periods (7 days for maceration and 72 h for Soxhlet extraction) were employed (Rojsanga and Gritsanapan, 2005; Rojsanga et al., 2006).

Large solvent volumes are characteristic for other conventional methods too. Shigwan et al. (2013) extracted berberine from Berberis aristata and B. tinctoria powdered stem bark (800 g) using hot extraction (50°C for 3 h) with 2,500 mL methanol (Shigwan et al., 2013).

Even though conventional methods are widely used in berberine extraction, a number of other different methods have been developed lately. This led to an improved extraction efficiency, a decreased extraction time and solvents' volumes used in the extraction. Thus, ultrasound assisted solvent extraction (USE), microwave-assisted solvent extraction (MAE), ultrahigh pressure extraction (UPE), and supercritical fluid extractions (SFE), pressurized liquid extraction (PLE) have been successfully used as alternative extraction techniques with better results when compared with classical extraction methods.

Ultrasonically and microwave-assisted extraction are considered green, simple, efficient, and inexpensive techniques (Alupului et al., 2009).

Teng and Choi (2013) extracted berberine from Rhizome coptidis by optimized USE. Using response surface methodology, they identified that the optimal extraction conditions were 59% ethanol concentration, at 66.22°C within 46.57 min. A decrease in the extraction time (39.81 min) was obtained by Chang (2013). He used the combination of ionic liquids solutions as green solvents with USE to extract berberine from Coptis chinensis in order to apply an environmentally friendly approach (Chang, 2013). Moreover, in their study, Xu et al. (2017) compared several extraction tehniques like USE, distillation, and Soxhlet extraction in order to establish an high-efficient method for phellodendrine, berberine, and palmatine extraction from fresh Phellodendron bark (Cortex phellodendri). In the case of berberine, the combination of simple or acidified solvent (water, ethanol, and methanol) with the adjustment of the specific setting characteristics to each extraction type enabled them to determine the highest extraction yield. They concluded that the use of USE and hydrochloric acid-acidified methanol were the most efficient in extracting berberine. The USE extraction yield was significantly higher when compared to distillation and Soxhlet extraction, with values of ~100 mg/g toward 50 and 40 mg/g berberine, respectively (Xu et al., 2017).

The important reduction in organic solvent and extraction time determined the increasing interest in MAE, too. Lately, MAE was used as a green and cost-effective alternative to conventional methods. Using central composite design, Satija et al. (2015) successfully optimized the MAE parameters in terms of irradiation power, time, and solvent concentration to extract berberine form Tinospora cardifolia. They compared two classical extraction techniques like maceration and Soxhlet extraction with MAE under optimized conditions (60% irradiation power, 80% ethanol concentration, and 3 min extraction time). The results showed that MAE extraction had the highest yield of berberine content with 1.66% (w/w) while Soxhlet and maceration had 1.04 and 0.28% (w/w), respectively. Their study is emphasizing the dramatic time reduction in case of MAE (3 min) when compared with Soxhlet extraction (3 h) and maceration (7 days) together with solvent and energy consumption (Satija et al., 2015).

Another novel extraction technique considered to be environmentally friendly is UPE. The interest toward this extraction technique is increasing because it presents several advantages toward classical extraction techniques like increased extraction yields, higher quality of extracts, less extraction time, and decreased solvent consumption (Xi, 2015). These are achieved at room temperature by applying different pressure levels (from 100 to 600 MPa) between the interior (higher values) and the exterior of cells (lower values) in order to facilitate the transfer of the bioactive compounds through the plant matrices in the extraction solvent (Liu et al., 2006, 2013). In the study regarding berberine content in Cortex phellodendri, Guoping et al. (2012) made a comparison between UPE, MAE, USE, and heat reflux extraction techniques. They observed that the higher extraction yield and the lower extraction time was obtained in case of UPE with 7.7 mg/g and 2 min extraction time toward reflux, USE and MAE with 5.35 mg/g and 2 h, 5.61 mg/g and 1 h. and 6 mg/g and 15 min, respectively (Guoping et al., 2012).

Super critical fluid extraction is another environmentally friendly efficient technique used in phytochemical extraction. Because the extraction is performed in the absence of light and oxygen, the degradation of bioactive compounds is reduced. Also, the inert and non-toxic carbon dioxide used as a main extraction solvent in combination with various modifiers (e.g., methanol) and surfactants (e.g., Tween 80) at lower temperatures and relatively low pressure, allows the efficient extraction of bioactive compounds (Liu et al., 2006; Farías-Campomanes et al., 2015). In case of berberine extraction from the powdered rhizome of Coptis chinensis Franch, the highest recovery of berberine was obtained when 1,2-propanediol was used as a modifier of supercritical CO₂ (Liu et al., 2006).

Pressurized liquid extraction, also known as pressurized fluid extraction, pressurized solvent extraction, and accelerated solvent extraction (ASE) is considered a green technology used for compounds extraction from plants (Mustafa and Turner, 2011). Compared with conventional methods, PLE increases the extraction yield, decreases time and solvent consumption, and protects sensitive compounds. In their study, Schieffer and Pfeiffer (2001) compared different extraction techniques like PLE, multiple USE, single USE, and Soxhlet extraction in order to extract berberine from goldenseal (Hydrastis canadensis). When compared in terms of extraction yield the results are comparable, ~42 mg/g berberine, except single USE with slightly lower content (37 mg/g berberine). Big differences were observed in the extraction time, PLE requiring only 30 min for a single sample extraction compared to 2 h for multiple extraction techniques or 6 h for Soxhlet extraction (Schieffer and Pfeiffer, 2001).

When referring to berberine extraction from biological samples, the extraction process is relatively simple and involves several steps like sample mixing with extraction solvents (e.g., methanol, acetone, acetonitrile), vortex, centrifugation followed by supernatant evaporation under nitrogen stream (Table 3). Other extraction techniques like solid phase extraction (SPE) can also be applied.

Analytical techniques

After extraction and purification, the separation and quantification of berberine are commonly resolved by chromatographic methods. According to literature studies, berberine determination in plants was predominantly performed using methods like UV spectrophotometry (Joshi and Kanaki, 2013), HPLC (Babu et al., 2012; Akowuah et al., 2014), HPTLC and TLC (Rojsanga and Gritsanapan, 2005; Arawwawala and Wickramaar, 2012; Samal, 2013), capillary electrophoresis (Du and Wang, 2010), while berberine content in biological fluids was mainly achieved by using LC-MS (Deng et al., 2008; Feng et al., 2010), UPLC-MS (Liu M. et al., 2015; Liu L. et al., 2016), UHPLC/Q-TOF-MS (Wu et al., 2015).

UV-Vis spectrophotometry can be considered as one of the most rapid detection methods for berberine quantitative analysis from plant extracts. Based on the Beer-Lambert law, berberine concentration can be determined according to its absorption maxima at 348 nm. Joshi and Kanaki (2013) quantified berberine in Rasayana churna samples in the range of 2–20 μg/mL, the interference with other compounds being avoided by the specific isolation of the alkaloid fraction (Joshi and Kanaki, 2013).

Next, high-performance liquid chromatography (HPLC) is a versatile, robust, and widely used technique for the qualitative and quantitative analysis of natural products (Sasidharan et al., 2011). This approach is widely used in berberine identification and quantification. Generally, the choices of stationary phase in berberine separation are variants of C18-based silica column (Table 3) with a mobile phase consisting of simple or acidified solvents like water, methanol, or acetonitrile, used as such or in combination with phosphate buffers. Normally, the identification and separation of berberine can be accomplished using either isocratic or gradient elution system. Berberine identification is further accomplished using high sensitivity UV or DAD (diode array detectors) detectors. For example, Shigwan et al. (2013) developed in his study a reverse phase HPLC method with photodiode array detection (PDA) to quantify berberine from Berberis aristata and B. tinctoria. They used a Unisphere-C18 column (5 μm, 4.6 × 150 mm) with an isocratic gradient of acidified water (with 0.1% trifluoroacetic acid) and acetonitrile (60:40, v/v) to elute berberine within 5 min. The developed method was reproducible, validated, precise, and specific for berberine quantification (with a concentration range between 0.2 and 150 μg/mL; Shigwan et al., 2013).

Two other commonly used techniques in berberine quantification are thin layer chromatography (TLC) and high performance thin layer chromatography (HTPLC). Sometimes, these methods are preferred over HPLC, offering the possibility of running several samples simultaneously along with the use of small amount of both samples and mobile phases (Samal, 2013). For these reasons, Samal (2013) used an HPTLC method to quantify berberine from A. mexicana L. using toluene and ethyl acetate (9:3, v/v) as mobile phases, and a silica gel plate as stationary phase, they developed a simple, rapid, and cost-effective method for berberine quantification. The LOD (0.120 μg) and LOQ (0.362 μg) of the method are in accordance with high-quality requirements.

Following the same principles (small sample volume, high separation efficiency, and short analysis time), capillary electrophoresis (CE) was successfully used in berberine analysis. Du and Wang (2010) used CE with end-column electrochemiluminescence (ECL) detection for berberine analysis in both tablets and Rhizoma coptidis. Using a 4 min analysis time, a small sample volume (3.3 nL) and a LOD of (5 × 10⁻⁹ g/mL), the developed method proved to be highly sensitive and with good resolution (Du and Wang, 2010).

Besides UV, HPLC, HTPLC, TLC, and CE, other detection methods like liquid chromatography coupled with mass spectrometry (LC/MS) are currently employed to quantify berberine in biological fluids. Generally, it is considered a powerful technique for the analysis of complex samples because it offers rapid and accurate information about the structural composition of the compounds, especially when tandem mass spectrometry (MSⁿ) is applied. For example, Xu et al. (2015) developed a sensitive an accurate LC-MS/MS method to determine berberine and other seven components in rat plasma using multiple reactions monitoring (MRM) mode. Compounds separation was optimized using six different types of reverse-phase columns, and two different mobile phases (methanol–water and acetonitrile–water with different additives). Additives like formic acid, acetic acid, and ammonium acetate were added in different concentrations as follows: 0.1, 0.5, 1, and 2% for formic acid, 0.1, 0.5, 1, and 2% for acetic acid and 0.0001, 0.001, 0.01 mol/L for ammonium acetate. The method was also tested in terms of specificity, linearity, lower limit of quantification (LLOQ), precision, accuracy, and stability (Xu et al., 2015).

Antioxidant effect

Under normal conditions, the body maintains a balance between the antioxidant and pro-oxidant agents (reactive oxygen species—ROS and reactive nitrogen species—RNS; Rahal et al., 2014).

The imbalance between pro and antioxidants occurs in case of increased oxidative stress (Bhattacharyya et al., 2014).

The oxidative stress builds up through several mechanisms: an increase in the production of reactive species, a decrease in the levels of enzymes involved in blocking the actions of pro-oxidant compounds, and/or the decrease in free radical scavengers (Pilch et al., 2014).

An experimental study demonstrated the effect of berberine on lipid peroxidation after inducing chemical carcinogenesis in small animals (rats). An increase in LPO (lipid peroxidation) was observed after carcinogenesis induction, but also its significant reversal after berberine administration (30 mg/kg). Berberine shows therefore at least partial antioxidant properties, due to its effect on lipid peroxidation (Thirupurasundari et al., 2009).

Other mechanisms involved in the antioxidant role of berberine are: ROS/RNS scavenging, binding of metals leading to the transformation/oxidation of certain substances, free-oxygen removal, reducing the destructiveness of superoxide ions and nitric oxide, or increasing the antioxidant effect of some endogenous substances. The antioxidant effect of berberine was comparable with that of vitamin C, a highly-potent antioxidant (Shirwaikar et al., 2006; Ahmed et al., 2015).

The increase in blood sugar leads to oxidative stress not by generating oxygen reactive species but by impairing the antioxidant mechanisms. Administration of berberine to rats with diabetes mellitus increased the SOD (superoxide dismutase) activity and decreased the MDA (malondialdehyde) level (marker of lipid peroxidation). This antioxidant effect of berberine could explain the renal function improvement in diabetic nephropathy (Liu et al., 2008b).

The oxidative stress plays an important role in the pathogenesis of many diseases. The beneficial effect of berberine is presumed to reside mostly in its antioxidant role.

Cardiovascular effects of berberine

Effect on cardiac contractility

The beneficial effect of berberine in cardiac failure was demonstrated in a study on 51 patients diagnosed with NYHA (New York Heart Association) III/IV cardiac failure with low left ventricular ejection fraction (LVEF) and premature ventricular contractions and/or ventricular tachycardia. These patients received tablets containing 1.2 g berberine/day, together with conventional therapy (diuretics, ACEI—angiotensin-converting-enzyme inhibitors, digoxin, nitrates) for 2 weeks. An increase in LVEF was observed in all patients after this period, but also a decrease in the frequency and complexity of premature ventricular contractions. The magnitude of the beneficial effect was in direct proportion with the plasma concentration of berberine (Zeng, 1999).

The cardioprotective effect during ischemia

Berberine can provide cardio-protection in ischemic conditions by playing various roles at different levels: modulation of AMPK (AMP—activated kinase) activity, AKT (protein kinase B) phosphorylation, modulation of the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway and of GSK3β (glycogen synthase kinase 3β; Chang et al., 2016). AMPK is an important enzyme playing an essential role in cellular metabolism and offering protection in ischemic conditions by adjusting the carbohydrate and lipid metabolism, the function of cell organelles (mitochondria, endoplasmic reticulum) and the apoptosis (Zaha et al., 2016).

Berberine activates the PI3K (phosphoinositide 3-kinase)/AKT pathway which is considered a compensatory mechanism limiting the pro-inflammatory processes and apoptotic events in the presence of aggressive factors. The activation of this pathway is associated with a reduction of the ischemic injury through the modulation of the TLR4 (toll-like receptor 4)-mediated signal transduction (Hua et al., 2007).

Several supporting data indicate that the JAK2/STAT3 signaling plays an important role in cardioprotection against ischemia-reperfusion injury (Mascareno et al., 2001).

GSK3β is a serine/threonine protein-kinase, an enzyme involved in reactions associated to important processes at the cellular level: metabolization, differentiation, proliferation, and apoptosis. Berberine inhibits this kinase, thereby exercising its cardioprotective effect (Park et al., 2014).

Effects on the endothelium

Berberine induces endothelial relaxation by increasing NO production from arginine through the activity of eNOS (endothelial nitric oxide synthase) which is considered a key element in the vasodilation process. Besides increasing the NO level, it also up-regulates eNOS mRNA. Furthermore, berberine facilitates the phosphorylation of eNOS and its coupling to HSP 90 (heat shock proteins), which consequently increases NO production (Wang et al., 2009).

Moreover, berberine reduces endothelial contraction by reducing COX-2 expression. Any imbalance in COX 1 or 2 activity may alter the ratio between prothrombotic/antithrombotic and vasodilator/vasoconstrictor effects (Liu L. et al., 2015).

The beneficial effect of berberine on the TNFα-induced endothelial contraction was also recorded, as well as an increase in the level of PI3K/AKT/eNOS mRNA (Xiao et al., 2014).

The role of berberine in atherosclerosis

Atherogenesis is a consequence of high blood lipid levels and is associated with inflammatory changes in the vascular wall. Berberine interferes with this process by up-regulating the expression of SIRT1 (silent information regulator T1) and by inhibiting the expression of PPARγ (peroxisome proliferator-activated receptor-γ). SIRT1 is a NAD-dependent deacetylase. The SIRT1 enzyme has many targets (PPARγ, p53), all playing different roles in atherogenesis (Chi et al., 2014).

The role of berberine in lipid metabolism

The effects of berberine on lipid metabolism are also the consequence of its effects on LDL cholesterol receptors. On one hand, these receptors are stabilized by an extracellular signal-regulated kinase (ERK)-dependent pathway, and on the other, berberine increases the activity of LDL receptors through the JNK pathway (Cicero and Ertek, 2009).

Moreover, berberine has an effect on ACAT (cholesterol acyltransferases), a class of enzymes that transform cholesterol into esters, thus playing an essential role in maintaining cholesterol homeostasis in different tissues. There are two types of ACAT enzymes, ACAT1, and ACAT2. ACAT1 is a ubiquitous enzyme, while ACAT2 can be found only in hepatic cells and enterocytes. Berberine influences the activity of ACAT2 without an effect on ACAT1, therefore reducing the intestinal absorption of cholesterol and decreasing its plasmatic level (Chang et al., 2009; Wang et al., 2014).

The hypolipidemic effect of berberine is also a result of its action on PCSK9 (proprotein convertase subtilisin kexin 9). This enzyme can attach itself to LDL receptors, leading to a decrease in LDL metabolization and an increase in its blood level (Xiao et al., 2012).

In a clinical trial, 63 patients with dyslipidemia were randomly divided in three groups. The first group was treated with berberine (1,000 mg/day), the second with simvastatin (20 mg/day) and the third with a combination of berberine and simvastatin. The authors reported a 23.8% reduction in LDL-C levels in patients treated with berberine, a 14.3% reduction in those treated with simvastatin and a 31.8% LDL-C reduction in the group treated with both simvastatin and berberine. This result demonstrates that berberine can be used alone or in association with simvastatin in the treatment of dyslipidemia (Kong et al., 2008).

The role of berberine in glucose metabolism

Many studies demonstrated that berberine lowers blood sugar, through the following mechanisms:

• - Inhibition of mitochondrial glucose oxidation and stimulation of glycolysis, and subsequently increased glucose metabolization (Yin et al., 2008a).

• - Decreased ATP level through the inhibition of mitochondrial function in the liver, which may be the probable explanation of gluconeogenesis inhibition by berberine (Xia et al., 2011).

• - Inhibition of DPP 4 (dipeptidyl peptidase-4), a ubiquitous serine protease responsible for cleaving certain peptides, such as the incretins GLP1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide); their role is to raise the insulin level in the context of hyperglycemia. The DPP4 inhibition will prolong the duration of action for these peptides, therefore improving overall glucose tolerance (Al-masri et al., 2009; Seino et al., 2010).

Berberine has a beneficial effect in improving insulin resistance and glucose utilization in tissues by lowering the lipid (especially triglyceride) and plasma free fatty acids levels (Chen et al., 2011).

The effect of berberine (1,500 mg day) on glucose metabolism was also demonstrated in a pilot study enrolling 84 patients with type 2 diabetes mellitus. The effect, including on HbA1c, was comparable to that of metformin (1,500 mg/day), one of the most widely used hypoglycemic drugs. In addition, berberine has a favorable influence on the lipid profile, unlike metformin, which has barely any effect (Yin et al., 2008b).

Hepatoprotective effect of berberine

The hepatoprotective effect of berberine was demonstrated on lab animals (mice), in which hepatotoxicity was induced by doxorubicin. Pretreatment with berberine significantly reduced both functional hepatic tests and histological damage (inflammatory cellular infiltrate, hepatocyte necrosis; Zhao et al., 2012).

The mechanism by which berberine reduces hepatotoxicity was also studied on CCl₄ (carbon tetrachloride)-induced hepatotoxicity. Berberine lowers the oxidative and nitrosamine stress and also modulates the inflammatory response in the liver, with favorable effects on the changes occurring in the liver. Berberine prevents the decrease in SOD activity and the increase in lipid peroxidation and contributes to the reduction in TNF-α, COX-2, and iNOS (inducible nitric oxide synthase) levels. The decrease in transaminase levels supports the hypothesis according to which berberine helps maintain the integrity of the hepatocellular membrane (Domitrović et al., 2011).

Nephroprotective effect of berberine

The chronic kidney damage occurring in time in patients with HT (hypertension) and DM (diabetes mellitus) is well known; it is mainly due to the atherosclerosis of the renal artery, caused by inflammation and oxidative stress. The protective effect of berberine on kidneys was studied on 69 patients suffering from both HT and DM, with blood pressure and blood sugar levels controlled with conventional medication. The patients received 300 mg berberine/day for 24 months, with 2-week interruptions every 5 months. The authors recorded lower CRP (C-reactive protein), MDA and SOD levels after treatment, but without significant changes in creatinine, arterial pressure, or glycaemia levels. These results support the renal protective effect of berberine through its anti-inflammatory and antioxidant effects (Dai et al., 2015).

Another animal study tested the renoprotective effect of berberine after administration of HgCl₂ (mercury chloride). This substance induces hepato-renal damage by increasing the oxidative stress (increases lipid peroxidation and NO levels, and lowers glutathione and SOD levels as well as the activity of other protective enzymes). Administration of HgCl₂ increased the AST (aspartate aminotransferase), ALT (alanine aminotransferase), and ALP (alkaline phosphatase) levels, compared to the control group. However, pretreatment with berberine lowered these enzymes significantly. In addition, both urea and creatinine levels were significantly increased in the HgCl₂ group vs. the control group, and again pretreatment with berberine prevented these changes. Additionally, the authors recorded higher pro-oxidant and lower antioxidant levels in the intervention group. These data support the hepatic and renal protective effects of berberine. Other studies performed on animal models with CCl₄₋induced hepatotoxicity demonstrated the same effect (Othman et al., 2014).

In addition, berberine can lower the nephrotoxicity caused by cisplatine. In an animal study, berberine was administered in progressive doses of 1, 2, 3 mg/kg, orally, for 2 successive days, starting 2 days after cisplatine administration. After the last doses of berberine, the animals were sacrificed and the kidneys were examined by the pathologist. The results showed significant histological improvement and a reduction in NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells), TNF α, COX2 an iNOS levels, all of which support the anti-inflammatory effect of berberine (Domitrović et al., 2013).

Immunomodulatory effect of berberine

The immunomodulatory effect of berberine was demonstrated in many experimental and clinical contexts.

In an experimental autoimmune myocarditis model, berberine contributed to mitigate the cardiac damage by: limiting the rise in anticardiac myosin antibodies, modulating the activity of certain STATs and blocking Th1 and Th2 cell differentiation, which play an important role in the pathogenesis of myocarditis (Liu X. et al., 2016).

Experimental autoimmune neuritis is an experimental animal model equivalent to the Guillain-Barre syndrome in humans. This neurologic syndrome is characterized by autoimmune injury of the peripheral nervous system. The beneficial effect of berberine on this animal model resided in its influence on cellular and humoral immunity through the inhibition of lymphocyte proliferation (especially CD4), and the decrease in pro-inflammatory cytokines (IL-6 and TNF α; Li et al., 2014).

Experimental autoimmune encephalomyelitis is an established model of multiple sclerosis. Multiple sclerosis is a one of the most common diseases of the central nervous system (CNS) and involves neurodegenerative and inflammatory processes, and autoimmune demyelination (Ransohoff et al., 2015). The blood-brain barrier permeability and changes in matrix metalloproteinase (MMP) levels in the cerebrospinal fluid and brain were studied using this model (Ma et al., 2010). MMPs may be involved in demyelination and their activity in tissues depends on the balance between their level and their tissue inhibitors. MMP2 and MMP9 are the main endoproteinases involved in the migration of lymphocytes in CNS and in altering the BBB (blood brain barrier) (Avolio et al., 2003). Berberine has a beneficial effect in experimental autoimmune encephalomyelitis by inhibiting the activity of MMP9, reducing BBB permeability and, consecutively, by decreasing the inflammatory cellular infiltration of the CNS (Ma et al., 2010).

The current therapy used for inflammatory bowel diseases, including glucocorticoids and immunosuppressive agents, has a low level of safety. The effect of berberine was studied in combination with 5-ASA (5-aminosalicylic acid) vs. 5-ASA alone using an experimental animal model with DSS (dextran sulfate sodium)-induced colitis. The authors analyzed the level of proinflammatory cytokines in the animal gut. A decrease in COX2, IL6, and IL23 mRNA levels was observed in animals treated only with 5-ASA, whereas animals treated with both 5-ASA and berberine had a reduction in mRNA levels for COX2, IL6, IL23 as well as for TNF alfa and IL12b. This beneficial effect could partially be attributed to the inhibition of NF-kB and the reduction in JAK2 phosphorylation (through the influence on the JAK/STAT pathway) by both 5-ASA and berberine (Li et al., 2015; Figure 3).

Figure 3

Another study demonstrated that berberine increases the corticosteroid level in rats with experimentally-induced colitis. This engendered the theory that its beneficial effect may also be attributed to the increase in endogenous glucocorticoid levels, compounds with well-known therapeutic effect in inflammatory bowel disease (Minaiyan et al., 2011).

Conclusion

A review of the available scientific literature shows that the traditional medical uses of berberine-containing plants have been evaluated by modern pharmacological studies. Different species of berberine-rich plants have multiple pharmacological and therapeutic actions, such as antioxidant and immunomodulatory effects, protective action on the cardiovascular system, liver and kidney, endothelial relaxation, regulator on glucose metabolism and atherosclerosis, which can all be explained by the presence of berberine as well as other phyto constituents (when dealing with berberine-containing plant extracts). Moreover, the effects of berberine vary according to its origin (different plants or pharmaceutical products) and its concentration, depending on the very diverse extraction and detection techniques already described. Over time, modern extraction techniques were increasingly preferred to classical ones. Since classical methods are generally time- and solvent-consuming processes, modern extraction techniques such as USE, MAE, UPE, SFE, and PLE are seen as better alternatives to overcome these limitations. Furthermore, berberine, due to its antioxidant and anti-inflammatory effects, has several clinical applications in many disorders, from inflammatory conditions to the metabolic syndrome. However, there are some traditional uses that have not yet been completely elucidated, and further studies are needed. Therefore, extensive studies on the potential of plants containing berberine that have shown aforementioned pharmacological activities should go through additional in vitro and in vivo studies.

References

• 1

  AbbasiA. M.DastagirG.HussainF.SanaullahP. (2005). Ethnobotany and marketing of crude drug plants in district Haripur, Pakistan. Pak. J. Plant Sci.11, 103–114.

  • Google Scholar

• 2

  AbbasiA. M.KhanM. A.AhmadM.ZafarM.JahanS.SultanaS. (2010). Ethnopharmacological application of medicinal plants to cure skin diseases and in folk cosmetics among the tribal communities of North-West Frontier Province, Pakistan. J. Ethnopharmacol. 128, 322–335. 10.1016/j.jep.2010.01.052

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 3

  AbbasiA. M.KhanM. A.AhmadM.ZafarM.KhanH.MuhammadN.et al. (2009). Medicinal plants used for the treatment of jaundice and hepatitis based on socio-economic documentation. Afr. J. Biotechnol. 8, 1643–1650.

  • Google Scholar

• 4

  Abou-DoniaA. H. A.El-DinA. A. S. (1986). Phytochemical study of Argemone mexicana L. grown in Egypt. Egypt. J. Pharm. Sci. 25, 1–5.

  • Google Scholar

• 5

  AcharyaK. P.RokayaM. B. (2005). Ethnobotanical survey of medicinal plants traded in the streets of Kathmandu valley. Sci. World3, 44–48.

  • Google Scholar

• 6

  AdeyemiA. A.GboladeA. A.MoodyJ. O.OgboleO. O.FasanyaM. T. (2010). Traditional anti-fever phytotherapies in Sagamu and Remo north districts in Ogun State, Nigeria. J. Herbs. Spices Med. Plants16, 203–218. 10.1080/10496475.2010.511075

  • CrossRef
  • Google Scholar

• 7

  AdjanohounJ. E.AboobakarN.DramaneK. (1996). Traditional Medicine and Pharmacopoeia: Contribution to Ethnobotanical and Floristic Studies in Cameroon. Porto-Novo: Technical and Research Commission (STRC) of the Organization of African Unity.

  • Google Scholar

• 8

  AhmedE.ArshadM.AhmadM.SaeedM.IshaqueM. (2004). Ethnopharmacological survey of some medicinally important plants of Galliyat Areas of NWFP, Pakistan. Asian J. Plant Sci. 3, 410–415. 10.3923/ajps.2004.410.415

  • CrossRef
  • Google Scholar

• 9

  AhmedT.GilaniA. U.AbdollahiM.DagliaM.NabaviS. F.NabaviS. M. (2015). Berberine and neurodegeneration: a review of literature. Pharmacol. Rep.67, 970–979. 10.1016/j.pharep.2015.03.002

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 10

  AhnD. K. (2003). Illustrated Book of Korean Medicinal Herbs. Seoul: Kyo-Hak Publishing, Kyohaksa.

  • Google Scholar

• 11

  AjaliU. (2000). Antibacterial activity of Enantia polycarpa bark. Fitoterapia71, 315–316. 10.1016/S0367-326X(99)00153-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 12

  AkowuahG. A.OkechukwuP. N.ChiamN. C. (2014). Evaluation of HPLC and spectrophotometric methods for analysis of bioactive constituent berberine in stem extracts of Coscinium fenestratum. Acta Chromatogr. 26, 243–254. 10.1556/AChrom.26.2014.2.4

  • CrossRef
  • Google Scholar

• 13

  Al-DouriN. A. (2000). A survey of medicinal plants and their traditional uses in Iraq. Pharm. Biol. 38, 74–79. 10.1076/1388-0209(200001)3811-BFT074

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 14

  AliM.ShahS. Z.KhanM. S.NazM. F. R.ZafarA. (2018). Ethnobotanical study on the weeds of wheat crop in district Swabi, Khyber Pakhtunkhwa, Pakistan. Int. J. Biosci. 12, 363–374. 10.12692/ijb/12.1.363-374

  • CrossRef
  • Google Scholar

• 15

  Al-masriI. M.MohammadM. K.TahaaM. O. (2009). Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J. Enzyme Inhib. Med. Chem. 24, 1061–1066. 10.1080/14756360802610761

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 16

  Al-Qura'nS. (2009). Ethnopharmacological survey of wild medicinal plants in Showbak, Jordan. J. Ethnopharmacol. 123, 45–50. 10.1016/j.jep.2009.02.031

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 17

  AlupuluiA.CalinescuI.LavricV. (2009). Ultrasonic vs. microwave extraction intensification of active principles from medicinal plants. Chem. Eng. Trans. 17, 1023–1028. 10.3303/cet0917171

  • CrossRef
  • Google Scholar

• 18

  AndolaH. C.GairaK. S.RawalR. S.RawatM. S.BhattI. D. (2010a). Habitat-dependent variations in berberine content of Berberis asiatica Roxb. ex. DC. in Kumaon, Western Himalaya. Chem. Biodivers. 7, 415–420. 10.1002/cbdv.200900041

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 19

  AndolaH. C.RawalR. S.RawatM. S. M.BhattI. D.PurohitV. K. (2010b). Variations of berberine contents in Berberis pseudumbellata: a high value medicinal shrub of west Himalaya, India. Med. Plants Int. J. Phytomed. Relat. Ind. 2, 111–115. 10.5958/j.0975-4261.2.2.017

  • CrossRef
  • Google Scholar

• 20

  AndolaH. C.RawalR. S.RawatM. S. M.BhattI. D.PurohitV. K. (2010c). Analysis of berberine content using HPTLC fingerprinting of root and bark of three Himalayan Berberis species. Asian J. Biotechnol. 2, 239–245. 10.3923/ajbkr.2010.239.245

  • CrossRef
  • Google Scholar

• 21

  AnesiniC.PerezC. (1993). Screening of plants used in Argentine folk medicine for antimicrobial activity. J. Ethnopharmacol. 39, 119–128. 10.1016/0378-8741(93)90027-3

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 22

  ArawwawalaL. D. A. M.WickramaarW. A. N. (2012). Berberine content in Coscinium fenestratum (Gaertn.) Colebr grown in Sri Lanka. Pharmacologia3, 679–682. 10.5567/pharmacologia.2012.679.682

  • CrossRef
  • Google Scholar

• 23

  ArayneM. S.SultanaN.BahadurS. S. (2007). The berberis story: Berberis vulgaris in therapeutics. Pak. J. Pharm. Sci. 20, 83–92.

  • Google Scholar

• 24

  Atta-ur-RahmaAhmadH. (1992). An aporphine-benzylisoquinoline alkaloid from Berberis waziristanica. Phytochemistry31, 1835–1836. 10.1016/0031-9422(92)83163-S

  • CrossRef
  • Google Scholar

• 25

  AvolioC.RuggieriM.GiulianiF.LiuzziG. M.LeanteR.RiccioP.et al. (2003). Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes. J. Neuroimmunol. 136, 46–53. 10.1016/S0165-5728(03)00006-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 26

  BabuN. H. R.ThriveniH. N.VasudevaR. (2012). Influence of drying methods and extraction procedures on the recovery of berberine content in Coscinium fenestratum. J. Nat. Prod. Plant Resour. 2, 540–544.

  • Google Scholar

• 27

  BaharM.DengY.ZhuX.HeS.PandharkarT.DrewM. E.et al. (2011). Potent antiprotozoal activity of a novel semi-synthetic berberine derivative. Bioorg. Med. Chem. Lett.21, 2606–2610. 10.1016/j.bmcl.2011.01.101

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 28

  Baharvand-AhmadiB.BahmaniM.TajeddiniP.NaghdiN.Rafieian-KopaeiM. (2016). An ethno-medicinal study of medicinal plants used for the treatment of diabetes. J. Nephropathol. 5, 44–50. 10.15171/jnp.2016.08

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 29

  BaldazziC.LeoneM. G.CasiniM. L.TitaB. (1998). Effects of the major alkaloid of Hydrastis canadensis L., berberine, on rabbit prostate strips. Phyther. Res. 12, 589–591. 10.1002/(SICI)1099-1573(199812)12:8<589::AID-PTR347>3.0.CO;2-I

  • CrossRef
  • Google Scholar

• 30

  BapnaS.ChoudharyP. K.RamaiyaM.ChowdharyA. (2015). Antiplasmodial activity of Argemone mexicana: an in vivo and in vitro study. World J. Pharm. Res. 4, 1653–1663.

  • Google Scholar

• 31

  BeleM. Y.FochoD. A.EgbeE. A.ChuyongB. G. (2011). Ethnobotanical survey of the uses Annonaceae around mount Cameroon. Afr. J. Plant Sci. 5, 237–247.

  • Google Scholar

• 32

  BettiJ. L.CaspaR.AmbaraJ.KourogueR. L. (2013). Ethno-botanical study of plants used for treating malaria in a forest: savanna margin area, East region, Cameroon. Glob. J. Res. Med. Plants Indig. Med. 2, 692.

  • Google Scholar

• 33

  BettiJ. L.LejolyJ. (2009). Contribution to the knowledge of medicinal plants of the Dja Biosphere Reserve, Cameroon: plants used for treating jaundice. J. Med. Plants Res. 3, 1056–1065.

  • Google Scholar

• 34

  BhandariD. K.NathG.RayA. B.TewariP. V. (2000). Antimicrobial activity of crude extracts from Berberis asiatica stem bark. Pharm. Biol. 38, 254–257. 10.1076/1388-0209(200009)3841-AFT254

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 35

  BhattacharjeeS.TiwariK. C.MajumdarR.MisraA. K. (1980). Folklore medicine from district Kamrup (Assam). Bull. Medic. Ethno. Bot. Res.1, 447–460.

  • Google Scholar

• 36

  BhattacharyyaA.ChattopadhyayR.MitraS.CroweS. E. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 94, 329–354. 10.1152/physrev.00040.2012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 37

  BirdsallT. C. (1997). Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern. Med. Rev. 2, 94–103.

  • Google Scholar

• 38

  BonesiM.LoizzoM. R.ConfortiF.PassalacquaN. G.SaabA.MenichiniF.et al. (2013). Berberis aetnensis and B. libanotica: A comparative study on the chemical composition, inhibitory effect on key enzymes linked to Alzheimer's disease and antioxidant activity. J. Pharm. Pharmacol.65, 1726–1735. 10.1111/jphp.12172

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 39

  BorokiniT. I.ClementM.DicksonN. J.EdagboD. E. (2013). Ethnobiological survey of traditional medicine practice for fevers and headaches in Oyo State, Nigeria. Topclass J. Herb. Med. 2, 121–130.

  • Google Scholar

• 40

  BoseB. C.VijayvargiyaR.SaifiA. Q.SharmaS. K. (1963). Chemical and pharmacological studies on Argemone mexicana. J. Pharm. Sci. 52, 1172–1175. 10.1002/jps.2600521216

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 41

  BouquetA. (1969). Féticheurs et Médecines Traditionnelles du Congo (Brazzaville). Mém. O.R.S.T.O.M. (Paris: Office la Rech. Sci. Tech. outre-mer) 36, 282.

  • Google Scholar

• 42

  BouquetA.DebrayM. (1974). Plantes Médicinales de la Côte d'Ivoire. Paris Off. la Rech. Sci. Tech.Paris: Outre Mer 231p. (Travaux Doc. l'ORSTOM no. 32) Illus., col. illus. Geog 5.

  • Google Scholar

• 43

  BownD. (1995). Encyclopaedia of Herbs and Their Uses. London: Dorling Kindersley London.

  • Google Scholar

• 44

  BurkillH. M. (1985). The Useful Plants of West Tropical Africa. London: Royal Botanic Gardens, Kew.

  • Google Scholar

• 45

  BushraI.KishwarS.QureshiR. A.SaddiqaM. (2000). A checklist of plants of Bhogarmang, Siran Valley NWFP, Pakistan. Hamdard Med. 43, 62–76.

  • Google Scholar

• 46

  BuzasA.EgnellC. (1965). On the presence of quinidine in addition to berberine alkaloids in the barks of Enantia pilosa and Enantia polycarpa (Annonaceae). Ann. Pharm. Fr. 23, 351.

  • Google Scholar

• 47

  CastlemanM. (1991). The Healing Herbs: The Ultimate Guide to the Curative Powers of Nature's Medicine.Emmaus: Rodale Press.

  • Google Scholar

• 48

  ChakravartiK. K.DharD. C.SiddiquiS. (1950). Alkaloidal constituents of the bark of Berberis aristata. J. Sci. Ind. Res. 9, 161–164.

  • Google Scholar

• 49

  ChanC.-O.ChuC.-C.MokD. K.ChauF.-T. (2007). Analysis of berberine and total alkaloid content in Cortex phellodendri by near infrared spectroscopy (NIRS) compared with high-performance liquid chromatography coupled with ultra-visible spectrometric detection. Anal. Chim. Acta592, 121–131. 10.1016/j.aca.2007.04.016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 50

  ChandraP.PurohitA. N. (1980). Berberine contents and alkaloid profile of Berberis species from different altitudes. Biochem. Syst. Ecol. 8, 379–380. 10.1016/0305-1978(80)90040-X

  • CrossRef
  • Google Scholar

• 51

  ChangT.-Y.LiB.-L.ChangC. C.UranoY. (2009). Acyl-coenzyme A:cholesterol acyltransferases. Am. J. Physiol. Endocrinol. Metab. 297, E1–E9. 10.1152/ajpendo.90926.2008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 52

  ChangW.LiK.GuanF.YaoF.YuY.ZhangM.et al. (2016). Berberine pretreatment confers cardioprotection against ischemia-reperfusion injury in a rat model of type 2 diabetes. J. Cardiovasc. Pharmacol. Ther. 21, 486–494. 10.1177/1074248415627873

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 53

  ChangY. (2013). Ultrasonic-assisted extraction of berberine in ionic liquid. Pharm. Eng. 33, 1–4.

  • Google Scholar

• 54

  ChatterjeeD. R. (1951). Plant alkaloids. I. Berberis floribunda. J. Indian Chem. Soc. 28, 225–228.

  • Google Scholar

• 55

  ChatterjeeR.BanerjeeA. (1953). Plant alkaloids. V. Berberis lambertii. J. Indian Chem. Soc. 30, 705–707.

  • Google Scholar

• 56

  ChatterjeeR.GuhaM. P.Das GuptaA. K. (1952). Plant alkaloids. IV. Berberis himalaica and B. tinctoria. J. Indian Chem. Soc. 29, 921–924.

  • Google Scholar

• 57

  ChaudhuryR. H. N.GuhaA.ChaudhuryR.PalD. C. (1980). Ethnobotanical uses of herbaria-2. J. Econ. Taxon. Bot.1, 163–168.

  • Google Scholar

• 58

  ChenA. H. (1981). Studies on the analysis of alkaloids of Phellodendron wilsonii Hay. et Kaneh. Kaneh. Kexue Fazhan Yuekan9, 398–411.

  • Google Scholar

• 59

  ChenA. H. (1982). Applied studies on the alkaloids of Phellodendron wilsonii Hay. et Kaneh. II. the alkaloid contents in Taiwan plants. Kexue Fazhan Yuekan10, 279–286.

  • Google Scholar

• 60

  ChenC.YuZ.LiY.FichnaJ.StorrM. (2014). Effects of berberine in the gastrointestinal tract — a review of actions and therapeutic implications. Am. J. Chin. Med. 42, 1053–1070. 10.1142/S0192415X14500669

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 61

  ChenH. F.ChenC. M. (1988). Determination of berberine in crude and processed Chinese herb: Coptidis rhizoma and Phellodendri cortex. Zhonghua Yaoxue Zazhi40, 259–264.

  • Google Scholar

• 62

  ChenW. H.PangJ. Y.QinY.PengQ.CaiZ.JiangZ. H. (2005). Synthesis of linked berberine dimers and their remarkably enhanced DNA-binding affinities. Bioorg. Med. Chem. Lett. 15, 2689–2692. 10.1016/j.bmcl.2004.10.098

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 63

  ChenY.WangY.ZhangJ.SunC.LopezA. (2011). Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol. 2011, 1–8. 10.5402/2011/519371

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 64

  ChenY. Y.ChangF. R.WuY. C. (1996). Isoquinoline alkaloids and lignans from Rollinia mucosa. J. Nat. Prod. 59, 904–906. 10.1021/np960414z

  • CrossRef
  • Google Scholar

• 65

  ChevallierA. (1996). The Encyclopedia of Medicinal Plants. London: Dorling Kindersley.

  • Google Scholar

• 66

  ChhetriD. R.ParajuliP.SubbaG. C. (2005). Antidiabetic plants used by Sikkim and Darjeeling Himalayan tribes, India. J. Ethnopharmacol. 99, 199–202. 10.1016/j.jep.2005.01.058

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 67

  ChiL.PengL.PanN.HuX.ZhangY. (2014). The anti-atherogenic effects of berberine on foam cell formation are mediated through the upregulation of sirtuin 1. Int. J. Mol. Med. 34, 1087–1093. 10.3892/ijmm.2014.1868

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 68

  ChiangY. L.SuC. R.KuoP. C.DamuA. G.WuT. S. (2006). Two isoquinolones from the roots of Phellodendron amurense var. Wilsonii. Heterocycles68, 339–345. 10.3987/COM-05-10598

  • CrossRef
  • Google Scholar

• 69

  ChopraR. N.NayarS. I.ChopraI. C. (1986). Glossary of Indian Medicinal Plants (Including the Supplement). New Delhi: Canal of Scientific and Industrial Research.

  • Google Scholar

• 70

  CiceroA.ErtekS. (2009). Berberine: metabolic and cardiovascular effects in preclinical and clinical trials. Nutr. Diet Suppl.1, 1–10. 10.2147/NDS.S6084

  • CrossRef
  • Google Scholar

• 71

  CoffeyT. (1993). The History and Folklore of North American Wildflowers. New York, NY: Facts on File Limited.

  • Google Scholar

• 72

  DaiP.WangJ.LinL.ZhangY.WangZ. (2015). Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: evaluation via biochemical markers and color Doppler ultrasonography. Exp. Ther. Med.10, 869–876. 10.3892/etm.2015.2585

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 73

  de Almeida CostaO. (1935). (Mexican poppy) Argemone mexicana L. Rev. Flora Med. 1, 271–282.

  • Google Scholar

• 74

  DengA. J.QinH. L. (2010). Cytotoxic dihydrobenzophenanthridine alkaloids from the roots of Macleaya microcarpa. Phytochemistry71, 816–822. 10.1016/j.phytochem.2010.02.007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 75

  DengY.LiaoQ.LiS.BiK.PanB.XieZ. (2008). Simultaneous determination of berberine, palmatine and jatrorrhizine by liquid chromatography-tandem mass spectrometry in rat plasma and its application in a pharmacokinetic study after oral administration of coptis-evodia herb couple. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 863, 195–205. 10.1016/j.jchromb.2007.12.028

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 76

  DevS. (2006). A Selection of Prime Ayurvedic Plants Drugsancient- Modern Concordance. New Delhi: Anamaya Publishers.

  • Google Scholar

• 77

  DinN.DibongS. D.MpondoE. M.PrisoR. J.KwinN. F.NgoyeA. (2011). Inventory and identification of plants used in the treatment of diabetes in douala town (Cameroon). Eur. J. Med. Plants1, 60–73. 10.9734/EJMP/2011/273

  • CrossRef
  • Google Scholar

• 78

  DoepkeW.UlrichH.JimenezV. (1976). On the structure of a new alkaloid from Argemone mexicana. Z. Chem.16, 54–55.

  • Google Scholar

• 79

  DomitrovićR.CvijanovićO.Pernjak-PugelE.ŠkodaM.MikelićL.Crnčević-OrlićŽ. (2013). Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem. Toxicol. 62, 397–406. 10.1016/j.fct.2013.09.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 80

  DomitrovićR.JakovacH.BlagojevićG. (2011). Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl4-intoxicated mice. Toxicology280, 33–43. 10.1016/j.tox.2010.11.005

  • CrossRef
  • Google Scholar

• 81

  DonchevaT.KostovaN.YordanovaG.SaadiH.AkribF.DimitrovD.et al. (2014). Comparison of alkaloid profile from Glaucium corniculatum (Papaveraceae) of Algerian and Bulgarian origin. Biochem. Syst. Ecol. 56, 278–280. 10.1016/j.bse.2014.07.007

  • CrossRef
  • Google Scholar

• 82

  DuJ. X.WangM. (2010). Capillary electrophoresis determination of berberine in pharmaceuticals with end-column electrochemiluminescence detection. J. Chinese Chem. Soc. 57, 696–700. 10.1002/jccs.201000097

  • CrossRef
  • Google Scholar

• 83

  DukeJ. A.AyensuE. S. (1985). Medicinal Plants of China. Algonac, MI: Reference Publications.

  • Google Scholar

• 84

  DukeJ. A.Beckstrom-SternbergS. M. (1994). Dr. Duke's phytochemical and ethnobotanical databases. Available online at: http://www.ars-grin.gov/duke/plants.html (Accessed January 15, 2017).

  • Google Scholar

• 85

  DzhalilovD. R.GoryaevM. I.KruglykhinaG. K. (1963). Alkaloids from Berberis iliensis. I Izv. Akad. Nauk Kaz. SSR, Ser. Tekhn. i Khim. Nauk3, 15–19.

  • Google Scholar

• 86

  EgelsW. (1959). Papaver dubium var. lecoquii, a berberine-containing poppy. Planta Med. 7, 92–102. 10.1055/s-0028-1101592

  • CrossRef
  • Google Scholar

• 87

  EhiagbonareP. O.OnyibeJ. (2008). Conservation studies on four medicinal taxa of Southern Nigeria. Sci. Res. Essays3, 40–45.

  • Google Scholar

• 88

  El BeyrouthyM.ArnoldN.Delelis-DusollierA.DupontF. (2008). Plants used as remedies antirheumatic and antineuralgic in the traditional medicine of Lebanon. J. Ethnopharmacol. 120, 315–334. 10.1016/j.jep.2008.08.024

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 89

  EmbodenW. (1979). Narcotic Plants. New York, NY: Collier.

  • Google Scholar

• 90

  EmesM.AguilarA.ArguetaA.CanoL. (1994). Indigenous Medicinal Florae from México, Vol. II.

  • Google Scholar

• 91

  Eric BrussellD. (2004). A medicinal plant collection from Montserrat, West Indies. Econ. Bot. 58, S203–S220. 10.1663/0013-0001(2004)58[S203:AMPCFM]2.0.CO;2

  • CrossRef
  • Google Scholar

• 92

  EsseilyF.El EzzyM.Gali-MuhtasibH.SafiS.EsseilyJ.Diab-AssafM.et al. (2012). The ethanol fraction from the stem of Berberis libanotica inhibits the viability of adult T cell leukemia. Minerva Biotecnol. 24, 129–133.

  • Google Scholar

• 93

  EtminanM.GillS. S.SamiiA. (2005). Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Lancet. Neurol. 4, 362–365. 10.1016/S1474-4422(05)70097-1

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 94

  FabricantD. S.FarnsworthN. R. (2001). The value of plants used in traditional medicine for drug discovery. Environ. Heal. Perspect. Suppl. 109:69. 10.1289/ehp.01109s169

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 95

  Farías-CampomanesA. M.RostagnoM. A.Coaquira-QuispeJ. J.MeirelesM. A. A. (2015). Supercritical fluid extraction of polyphenols from lees: overall extraction curve, kinetic data and composition of the extracts. Bioresour. Bioprocess. 2, 45. 10.1186/s40643-015-0073-5

  • CrossRef
  • Google Scholar

• 96

  FengJ.XuW.TaoX.WeiH.CaiF.JiangB.et al. (2010). Simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in rat plasma by liquid chromatography-tandem mass spectrometry and application in pharmacokinetic studies after oral administration of traditional Chinese medicinal preparations containing Scutellaria-Coptis herb couple. J. Pharm. Biomed. Anal. 53, 591–598. 10.1016/j.jpba.2010.04.002

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 97

  FletcherM. T.TakkenG.BlaneyB. J.AlbertsV. (1993). Isoquinoline alkaloids and keto-fatty acids of Argemone ochroleuca and A. mexicana (Mexican poppy) seed. I. An assay method and factors affecting their concentration. Aust. J. Agric. Res. 44, 265–275. 10.1071/AR9930265

  • CrossRef
  • Google Scholar

• 98

  FogartyJ. E. (1990). A Barefoot Doctor's Manual: The American Translation of the Official Chinese Paramedical Manual.Philadelphia, PA: Running Press Book Publishers.

  • Google Scholar

• 99

  FongodA. G. (2014). Ethnobotany, indigenous knowledge and unconscious preservation of the environment: An evaluation of indigenous knowledge in South and Southwest Regions of Cameroon. Int. J. Biodivers. Conserv. 6, 85–99. 10.5897/IJBC2013.0637

  • CrossRef
  • Google Scholar

• 100

  FooteP. A. (1932). The alkaloids of Argemone alba Lestib. J. Am. Pharm. Assoc. 21, 246–248.

  • Google Scholar

• 101

  FosterS.DukeJ. A. (1990). A Field Guide to Medicinal Plants: Eastern and Central North America. Boston, MA: Houghton Mifflin Company.

  • Google Scholar

• 102

  FreileM.GianniniF.SortinoM.ZamoraM.JuarezA.ZacchinoS.et al. (2006). Antifungal activity of aqueous extracts and of berberine isolated from Berberis heterophylla. Acta Farm. Bonaer. 25, 83–88.

  • Google Scholar

• 103

  FysonP. F. (1975). Flora of the Nilgiri and Pulney Hill-Tops. Dehra Dun: Bishen Singh Mahendra Pal Singh and Periodical Experts.

  • Google Scholar

• 104

  GbileZ. O.SoladoyeM. O.AdesinaS. K. (1988). Plants in traditional medicine in West Africa. Monogr. Syst. Bot. Missouri Bot. Gard. 25, 343–349.

  • Google Scholar

• 105

  GboladeA. (2012). Ethnobotanical study of plants used in treating hypertension in Edo State of Nigeria. J. Ethnopharmacol. 144, 1–10. 10.1016/j.jep.2012.07.018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 106

  GertigH. (1964). Alkaloids of Eschscholtzia californica. I. Isolation and thin-layer chromatography of alkaloid fractions from roots. Acta Pol. Pharm. 21, 59–64.

  • Google Scholar

• 107

  GillL. S.AkinwumiC. (1986). Nigerian folk medicine: practices and beliefs of the Ondo people. J. Ethnopharmacol. 18, 257–266. 10.1016/0378-8741(86)90004-8

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 108

  Gorval'L. M.GrishkovetsV. I. (1999). Alkaloids of some species of the genus Berberis introduced into the Crimea. Chem. Nat. Compd. 35, 223–224. 10.1007/BF02234944

  • CrossRef
  • Google Scholar

• 109

  GovindasamyR.SimonJ.PuduriV. S.JulianiH. R.Asante-DarteyJ.ArthurH.et al. (2007). Retailers and Wholesalers of African Herbal and Natural Products: Case Studies from Ghana and Rwanda. Issues New Crop. New Uses. Virginia ASHP, 332–337.

  • Google Scholar

• 110

  GreathouseG. A. (1939). Alkaloids from Sanguinaria canadensis and their influence on growth of Phymatotrichum omnivorum. Plant Physiol. 14, 377. 10.1104/pp.14.2.377

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 111

  GrieveA. (1984). A Modern Herbal Penguin. Harmondsworth: Dover Publications Inc.

  • Google Scholar

• 112

  GrycováL.DostálJ.MarekR. (2007). Quaternary protoberberine alkaloids. Phytochemistry68, 150–175. 10.1016/j.phytochem.2006.10.004

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 113

  GuY.ZhangY.ShiX.LiX.HongJ.ChenJ.et al. (2010). Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta81, 766–772. 10.1016/j.talanta.2010.01.015

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 114

  GuopingL.JinhongL.ShuaiH.JianC.ZhongyiZ. (2012). Optimization for ultrahigh pressure extraction of berberine from Cortex phellodendri by central composite design-response surface methodology. J. Med. Plants Res.6, 3963–3970. 10.5897/JMPR11.1092

  • CrossRef
  • Google Scholar

• 115

  GuptaA. K.TandonN. (2004). Rev. Indian Med. Plants, Vol 4. Delhi: ICMR.

  • Google Scholar

• 116

  GurguelL.de CostaO. A.da SilvaR. D. (1934). Berberis laurina. Anatomic, histologic and chemical study. Bol. Assoc. Bras. pharm. 15, 11–20.

  • Google Scholar

• 117

  HabtemariamS. (2011). The therapeutic potential of Berberis darwinii stem-bark: quantification of berberine and in vitro evidence for Alzheimer's disease therapy. Nat. Prod. Commun. 6, 1089–1090.

  • Pubmed Abstract
  • Google Scholar

• 118

  HaisovaK.SlavikJ. (1975). On the minor alkaloids from Argemone mexicana L. Collect Czech. Chem. Commun.40, 1576–1578. 10.1135/cccc19751576

  • CrossRef
  • Google Scholar

• 119

  HakimS. A.MijovicV.WalkerJ. (1961). Distribution of certain poppy-fumaria alkaloids and a possible link with the incidence of glaucoma. Nature189, 198–201. 10.1038/189198a0

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 120

  HamayunM.KhanA.KhanM. A. (2003). Common medicinal folk recipes of District Buner, NWFP, Pakistan. Ethnobot. Leafl. 2003, 14.

  • Google Scholar

• 121

  HamonniereM.LeboeufA.ParisR. R. (1975). Alcaloïdes des annonacées: alcaloïdes de l'Enantia chlorantha. Plant. Med. Phytother. 9, 296–303.

  • Google Scholar

• 122

  HartwellJ. L. (1982). Plants Used Against Cancer. Lawrence, MA: Quarterman Publications. Inc.

  • Google Scholar

• 123

  HashmiK.HafizA. (1986). In vivo antibacterial activity of Berberis asiatica. J. Pak. Med. Assoc. 36, 5.

  • Pubmed Abstract
  • Google Scholar

• 124

  HaytaS.PolatR.SelviS. (2014). Traditional uses of medicinal plants in Elazig (Turkey). J. Ethnopharmacol. 154, 613–623. 10.1016/j.jep.2014.04.026

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 125

  HeJ.-M.MuQ. (2015). The medicinal uses of the genus Mahonia in traditional Chinese medicine: an ethnopharmacological, phytochemical and pharmacological review. J. Ethnopharmacol. 175, 668–683. 10.1016/j.jep.2015.09.013

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 126

  HenryT. A. (1949). The Plant Alkaloids, 4th Edn. Philadelphia, PA: Blakiston.

  • Google Scholar

• 127

  HirschhornH. H. (1981). Botanical remedies of South and Central America, and the Caribbean: an archival analysis. Part I. J. Ethnopharmacol. 4, 129–158. 10.1016/0378-8741(81)90032-5

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 128

  HoughtonP. J.ManbyJ. (1985). Medicinal plants of the Mapuche. J. Ethnopharmacol. 13, 89–103. 10.1016/0378-8741(85)90063-7

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 129

  HoughtonP. J.RenY.HowesM.-J. (2006). Acetylcholinesterase inhibitors from plants and fungi. Nat. Prod. Rep. 23, 181–199. 10.1039/b508966m

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 130

  HuaF.HaT.MaJ.LiY.KelleyJ.GaoX.et al. (2007). Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice is mediated through a phosphoinositide 3-kinase-dependent mechanism. J. Immunol. 178, 7317–7324. 10.4049/jimmunol.178.11.7317

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 131

  HuqM. E.IkramM. (1968). Alkaloids of Berberis petiolaris. Sci. Res. 5, 75–76.

  • Google Scholar

• 132

  HussainK.ShahazadA.Zia-ul-HussnainS. (2008). An ethnobotanical survey of important wild medicinal plants of Hattar district Haripur, Pakistan. Ethnobot. Leafl. 2008, 5.

  • Google Scholar

• 133

  HussainiF. A.ShoebA. (1985). Isoquinoline derived alkaloids from Berberis chitria. Phytochemistry24, 633. 10.1016/S0031-9422(00)80794-3

  • CrossRef
  • Google Scholar

• 134

  HutchensA. R. (1992). A Handbook of Native American Herbs: The Pocket Guide to 125 Medicinal Plants and Their Uses. Boston, MA: Shambhala Publications.

  • Google Scholar

• 135

  ImanshahidiM.HosseinzadehH. (2008). Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phyther. Res. 22, 999–1012. 10.1002/ptr.2399

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 136

  InbarajJ. J.KukielczakB. M.BilskiP.SandvikS. L.ChignellC. F. (2001). Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.) 1. Berberine. Chem. Res. Toxicol. 14, 1529–1534. 10.1021/tx0155247

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 137

  IrvineF. R. (1961). Woody Plants of Ghana. London: Oxford University Press.

  • Google Scholar

• 138

  IsholaI. O.OreagbaI. A.AdeneyeA. A.AdirijeC.OshikoyaK. A.OgunleyeO. O. (2014). Ethnopharmacological survey of herbal treatment of malaria in Lagos, Southwest Nigeria. J. Herb. Med. 4, 224–234. 10.1016/j.hermed.2014.08.001

  • CrossRef
  • Google Scholar

• 139

  IsrailovI. A.YunusovS. (1986). Alkaloids of four species of Argemone. Chem. Nat. Compd. 22, 189–192. 10.1007/BF00598384

  • CrossRef
  • Google Scholar

• 140

  JayaprakasamR.RaviT. K. (2014). Development and validation of HPTLC and RP-HPLC methods for the estimation of berberine in Coscinium fenestratum extract and its formulation. World J. Pharm. Res. 4, 206–218.

  • Google Scholar

• 141

  JhaR. N.PandeyM. B.SinghA. K.SinghS.SinghV. P. (2009). New alkaloids from Corydalis species. Nat. Prod. Res. 23, 250–255. 10.1080/14786410801996390

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 142

  JinC.ShanW. (1982). Quantitative determination of berberine in Coptis chinensis by TLC scanner method. Yaoxue Tongbao17, 145–146.

  • Google Scholar

• 143

  JiofackT.FokunangC.GuedjeN.KemeuzeV. (2009). Ethnobotany and phytomedicine of the upper Nyong valley forest in Cameroon. Afr. J. Pharm. Pharmacol. 3, 144–150.

  • Google Scholar

• 144

  JiofackT.FokunangC.KemeuzeV.FongnzossieE.TsabangN.NkuinkeuR.et al. (2008). Ethnobotany and phytopharmacopoea of the South-West ethnoecological region of Cameroon. J. Med. Plants Res. 2, 197–206.

  • Google Scholar

• 145

  JoshiA. R.JoshiK. (2007). Ethnomedicinal plants used against skin diseases in some villages of Kali Gandaki, Bagmati and Tadi Likhu watersheds of Nepal. Ethnobot. Leafl. 2007, 27.

  • Google Scholar

• 146

  JoshiH. R.KanakiN. (2013). Quantitative analysis of berberine in an ayurvedic formulation-Rasayana churna by UV spectrophotometry. J. Pharm. Sci. Biosci. Res. 3, 32–34.

  • Google Scholar

• 147

  JusiakL. (1967). Separation of Chelidonium majus alkaloids by countercurrent cascade extraction. II. Acta Pol. Pharm. 24, 65–70.

  • Google Scholar

• 148

  KadiriA. B. (2008). Evaluation of medicinal herbal trade (Paraga) in Lagos State of Nigeria. Ethnobot. Leafl. 2008, 90.

  • Google Scholar

• 149

  KalaC. P. (2006). Medicinal plants of the high altitude cold desert in India: diversity, distribution and traditional uses. Int. J. Biodivers. Sci. Manage. 2, 43–56. 10.1080/17451590609618098

  • CrossRef
  • Google Scholar

• 150

  KamalY. T.SinghM.TamboliE. T.ParveenR.AhmadS. (2011). Quantitative analysis of berberine in Berberis aristata fruits and in a traditional anti-inflammatory unani formulation by use of a validated HPLC method. Acta Chromatogr. 23, 157–168. 10.1556/AChrom.21.2013.1.11

  • CrossRef
  • Google Scholar

• 151

  KamigauchiM.IwasaK. (1994). Corydalis spp.: in vitro culture and the biotransformation of protoberberines, in Medicinal and Aromatic Plants VI. Biotechnology in Agriculture and Forestry, Vol 26, ed BajajY. P. S. (Berlin; Heidelberg: Springer), 93–105.

  • Google Scholar

• 152

  KarimovA. (1993). Berberis alkaloids. Chem. Nat. Compd. 29, 415–438. 10.1007/BF00630564

  • CrossRef
  • Google Scholar

• 153

  KarimovA.LutfullinK. L. (1986). Berberis alkaloids. 2'-N-methylisotetrandrine from Berberis oblonga. Khimiya Prir. Soedin. 2, 249–251.

  • Google Scholar

• 154

  KarimovA.MeliboevS.OlimovV.ShakirovR. (1993). Berberis alkaloids. XXX. Dynamics of alkaloid accumulation in Berberis integerrima and B. nummularia. Khimiya Prir. Soedin. 3, 472–473.

  • Google Scholar

• 155

  KarimovA.ShakirovR. (1993). Berberis alkaloids. XX. Alkaloids of Berberis iliensis. Khimiya Prir. Soedin. 1, 83–84. 10.1007/BF00631020

  • CrossRef
  • Google Scholar

• 156

  KariyoneT.KoisoR. (1971). Atlas of Medicinal Plants. Osaka: Takeda Chemical Industries.

  • Google Scholar

• 157

  KataokaM.TokuyamaE.MiyanagaY.UchidaT. (2008). The taste sensory evaluation of medicinal plants and Chinese medicines. Int. J. Pharm. 351, 36–44. 10.1016/j.ijpharm.2007.09.017

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 158

  KaurC.MianiS. (2001). Fruits and vegetables healthy foods for new millennium. Indian Hort.45, 29–32.

  • Google Scholar

• 159

  KayodeJ. (2006). Conservation of indigenous medicinal botanicals in Ekiti State, Nigeria. J. Zhejiang Univ. Sci. B7, 713–718. 10.1631/jzus.2006.B0713

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 160

  KhalmatovK. (1964). Khalmatov, Wild-Growing Medicinal Plants of Uzbekistan [in Russian] Tashkent. Meditsina.

  • Google Scholar

• 161

  KhamidovI.FaskhutdinovM.TelezhenetskayaM. V.KarimovA.LevkovichM. G.AbdullaevN. D.et al. (1996a). Berberis alkaloids. XXXIV. Turcomanine, a new alkaloid from Berberis turcomanica. Khimiya Prir. Soedin. 1, 74–76.

  • Google Scholar

• 162

  KhamidovI.KarimovA. K.TelezhenetskayaM. V.TashkhodzhaevB. (1996b). Berberis alkaloids. XXXV. Berberis turcomanica. Khimiya Prir. Soedin. 1, 107–109.

  • Google Scholar

• 163

  KhamidovI. I.AripovaS. F.KarimovA.YusupovM. M. (1997a). Berberis alkaloids. XL. An investigation of the alkaloids of Berberis thunbergii. Chem. Nat. Compd. 33, 599–599. 10.1007/BF02254817

  • CrossRef
  • Google Scholar

• 164

  KhamidovI. I.AripovaS. F.KarimovA. K. (2003). Berberis alkaloids. XLI. Alkaloids from leaves of cultivated Berberis oblonga. Chem. Nat. Compd. 39, 407. 10.1023/B:CONC.0000003429.41497.b6

  • CrossRef
  • Google Scholar

• 165

  KhamidovI. I.AripovaS. F.TelezhenetskayaM. V.KarimovA.DzhenberovI. (1997b). Berberis alkaloids XXXIX. New alkaloids from B. densiflora. Chem. Nat. Comp. 33, 323–325. 10.1007/BF02234886

  • CrossRef
  • Google Scholar

• 166

  KhamidovI. I.TashkhodzhaevB.AripovaS. F.TelezhenetskayaM. V.KarimovA. K. (1996c). Berberis alkaloids. XXXVII. Study of the alkaloids of B. oblonga and B. integerrima. Crystal structure of 8-trichloromethyldihydroberberine. Khimiya Prir. Soedin. 6, 889–893.

  • Google Scholar

• 167

  KhanI.NajeebullahS.AliM.ShinwariZ. K. (2016). Phytopharmacological and ethnomedicinal uses of the Genus Berberis (Berberidaceae): a review. Trop. J. Pharm. Res. 15, 2047–2057. 10.4314/tjpr.v15i9.33

  • CrossRef
  • Google Scholar

• 168

  KhanM. I.Sri HarshaP. S. C.GiridharP.RavishankarG. A. (2011). Berberine and lycopene profiling during the ontogeny of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms fruit. Curr. Sci. 100, 1225–1231.

  • Google Scholar

• 169

  KhanS. W.KhatoonS. (2007). Ethnobotanical studies on useful trees and shrubs of Haramosh and Bugrote valleys in Gilgit northern areas of Pakistan. Pak. J. Bot.39, 699–710.

  • Google Scholar

• 170

  KhodzhimatovM. (1989). Dikorastushchiye Lekarstvennuiye Rasteniya Tadzhikistana [Wild-Growing Medicinal Plants of Tadjikistan].

  • Google Scholar

• 171

  KingJ. (1898). King's American Dispensatory. Cincinatti, OH: Ohio Valley Company.

  • Google Scholar

• 172

  KirtikarK.BasuB. (1933). Indian Medicinal Plants, I. Allahabad: Lalit Mohan Basu and Co.

  • Google Scholar

• 173

  KirtikarK. R.BasuB. D. (1998). Indian Medicinal Plants, Vol 1. Allahabad: CSIR publication.

  • Google Scholar

• 174

  KiryakovH. G.DaskalovaE.GeorgievaA.KuzmanovB.EvstatievaL. (1982a). Alkaloids from Corydalis solida (L.) Swarz. Folia Med.24, 19–22.

  • Pubmed Abstract
  • Google Scholar

• 175

  KiryakovH. G.IskrenovaE.DaskalovaE.KuzmanovB.EvstatievaL. (1982b). Alkaloids of Corydalis slivenensis. Planta Med. 44, 168–170. 10.1055/s-2007-971432

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 176

  KnappJ. E.HusseinF. T.BealJ. L.DoskotchR. W.TomimatsuT. (1967). Isolation of two bisbenzylisoquinoline alkaloids from the rhizomes and roots of Xanthorhiza simplicissima. J. Pharm. Sci. 56, 139–141. 10.1002/jps.2600560129

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 177

  KončićM. Z.KremerD.SchühlyW.BrantnerA.KarlovićK.KaloderaZ. (2010). Chemical differentiation of Berberis croatica and B. vulgaris using HPLC fingerprinting. Croat. Chem. Acta83, 451–456.

  • Google Scholar

• 178

  KongW. J.WeiJ.ZuoZ. Y.WangY. M.SongD. Q.YouX. F.et al. (2008). Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism. 57, 1029–1037. 10.1016/j.metabol.2008.01.037

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 179

  KongY.XiaoJ.-J.MengS.-C.DongX.-M.GeY.-W.WangR.-F.et al. (2010). A new cytotoxic flavonoid from the fruit of Sinopodophyllum hexandrum. Fitoterapia81, 367–370. 10.1016/j.fitote.2009.11.003

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 180

  KosalecI.GregurekB.KremerD.ZovkoM.SankovićK.KarlovićK. (2009). Croatian barberry (Berberis croatica Horvat): a new source of berberine? analysis and antimicrobial activity. World J. Microbiol. Biotechnol. 25, 145–150. 10.1007/s11274-008-9860-x

  • CrossRef
  • Google Scholar

• 181

  KosinaP.GregorovaJ.GruzJ.VacekJ.KolarM.VogelM.et al. (2010). Phytochemical and antimicrobial characterization of Macleaya cordata herb. Fitoterapia81, 1006–1012. 10.1016/j.fitote.2010.06.020

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 182

  KostalovaD.BrazdovicovaB.JinH. Y. (1982). Alkaloids from the aboveground parts of Berberis koreana Palib. Farm. Obz. 51, 213–216.

  • Google Scholar

• 183

  KubotaM.KatsunoriM.MiyazawaY. (1980). Berberine contents in cultivated Coptis japonica Makino. Nagano-ken Eisei Kogai Kenkyusho Kenkyu Hokoku2, 22–27.

  • Google Scholar

• 184

  Kukula-KochW.MroczekT. (2015). Application of hydrostatic CCC–TLC–HPLC–ESI-TOF-MS for the bioguided fractionation of anticholinesterase alkaloids from Argemone mexicana L. roots. Anal. Bioanal. Chem. 407, 2581–2589. 10.1007/s00216-015-8468-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 185

  KulkarniS. K.DhirA. (2010). Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phyther. Res. 24, 317–324. 10.1002/ptr.2968

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 186

  KunwarR. M.AdhikariN. (2005). Ethnomedicine of Dolpa district, Nepal: the plants, their vernacular names and uses. Lyonia8, 43–49. 10.1186/1746-4269-2-27

  • CrossRef
  • Google Scholar

• 187

  KüpeliE.KoşarM.YeşiladaE.HüsnüK.BaşerC. (2002). A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sci. 72, 645–657. 10.1016/S0024-3205(02)02200-2

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 188

  LadinoO. J. P.SuárezL. E. C. (2010). Chemical constituents of the wood from Zanthoxylum quinduense Tul. (Rutaceae). Quim. Nova33, 1019–1021. 10.1590/S0100-40422010000500002

  • CrossRef
  • Google Scholar

• 189

  LaunertE. (1981). Edible and Medicinal Plants. London: Hamlyn.

  • Google Scholar

• 190

  LeeH. Y.KimC. W. (1999). Isolation and quantitative determination of berberine and coptisine from tubers of Corydalis ternata. Saengyak Hakhoechi30, 332–334.

  • Google Scholar

• 191

  LeoneM. G.CometaM. F.PalmeryM.SasoL. (1996). HPLC determination of the major alkaloids extracted from Hydrastis canadensis L. Phyther. Res. 10, S45–S46.

  • Google Scholar

• 192

  LiH.LiX. L.ZhangM.XuH.WangC. C.WangS.et al. (2014). Berberine ameliorates experimental autoimmune neuritis by suppressing both cellular and humoral immunity. Scand. J. Immunol. 79, 12–19. 10.1111/sji.12123

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 193

  LiW. L.ZhengH. C.BukuruJ.De KimpeN. (2004). Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. J. Ethnopharmacol. 92, 1–21. 10.1016/j.jep.2003.12.031

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 194

  LiY.-H.ZhangM.XiaoH.-T.FuH.-B.HoA.LinC.-Y.et al. (2015). Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodium-induced chronic colitis in C57BL/6 Mice. PLoS ONE10:e0144101. 10.1371/journal.pone.0144101

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 195

  LiuB.LiW.ChangY.DongW.NiL. (2006). Extraction of berberine from rhizome of Coptis chinensis Franch using supercritical fluid extraction. J. Pharm. Biomed. Anal. 41, 1056–1060. 10.1016/j.jpba.2006.01.034

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 196

  LiuF.LiZ.ShiX.ZhongM. (2011). Determination of berberine, palmatine and jatrorrhizine in rabbit plasma by liquid chromatography-electrospray ionization-mass spectrometry. J. Pharm. Biomed. Anal. 56, 1006–1015. 10.1016/j.jpba.2011.08.001

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 197

  LiuJ. (1992). Extraction of berbamine with water. Zhongguo Yaoxue Zazhi27, 290–291.

  • Google Scholar

• 198

  LiuL.LiuJ.HuangZ.YuX.ZhangX.DouD.et al. (2015). Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats. Biochem. Biophys. Res. Commun. 458, 796–801. 10.1016/j.bbrc.2015.02.028

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 199

  LiuL.WangZ. B.SongY.YangJ.WuL. J.YangB. Y.et al. (2016). Simultaneous determination of eight alkaloids in rat plasma by UHPLC-MS/MS after oral administration of Coptis deltoidea C.Y. Cheng et Hsiao and Coptis chinensis Franch. Molecules21, 1–15.

  • Pubmed Abstract
  • Google Scholar

• 200

  LiuM.SuX.LiG.ZhaoG.ZhaoL. (2015). Validated UPLC-MS/MS method for simultaneous determination of simvastatin, simvastatin hydroxy acid and berberine in rat plasma: application to the drug-drug pharmacokinetic interaction study of simvastatin combined with berberine after oral administratio. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1006, 8–15. 10.1016/j.jchromb.2015.09.033

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 201

  LiuS.ChenY.GuL.LiY.WangB.HaoJ.et al. (2013). Effects of ultrahigh pressure extraction conditions on yields of berberine and palmatine from Cortex phellodendri amurensis. Anal. Methods5, 4506. 10.1039/c3ay40784e

  • CrossRef
  • Google Scholar

• 202

  LiuW.LiuP.TaoS.DengY.LiX.LanT.et al. (2008b). Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch. Biochem. Biophys. 475, 128–134. 10.1016/j.abb.2008.04.022

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 203

  LiuW. H.HeiZ. Q.NieH.TangF. T.HuangH. Q.LiX. J.et al. (2008a). Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin. Med. J.121, 706–712.

  • Pubmed Abstract
  • Google Scholar

• 204

  LiuX.ZhangX.YeL.YuanH. (2016). Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model. Biomed. Pharmacother. 79, 222–230. 10.1016/j.biopha.2016.02.015

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 205

  LouY.YumingW.YanfenD.JidaS.HuangL. (1982). Extractive spectrophotometric determination of berberine. Yaowu Fenxi Zazhi2, 82–85.

  • Google Scholar

• 206

  LustJ. (2014). The Herb Book: The Most Complete Catalog of Herbs Ever Published.New York, NY: Courier Corporation.

  • Google Scholar

• 207

  MaX.JiangY.WuA.ChenX.PiR.LiuM.et al. (2010). Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. PLoS ONE5:e13489. 10.1371/journal.pone.0013489

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 208

  MaithaniA.ParchaV.KumarD. (2014). Quantitative estimation of berberine content of Berberis asiatica from different altitude of Garhwal Himalaya. Asian J. Pharm. Clin. Res.7, 165–167.

  • Google Scholar

• 209

  MajumderB.SchindraS. N.DuttaP. C. (1956). Occurrence of ceryl alcohol in Argemone mexicana. J. Indian Chem. Soc. 33, 351–352.

  • Google Scholar

• 210

  ManandharN. P. (2002). Plants and People of Nepal. Portland, OR: Timber Press.

  • Google Scholar

• 211

  ManskeR. H. F. (1939). The alkaloids of fumariaceous plants. XIX. Corydalis ophiocarpa Hook. f. et Thoms. Can. J. Res. Sect. B Chem. Sci. 17, 51–56. 10.1139/cjr39b-009

  • CrossRef
  • Google Scholar

• 212

  MarekR.SeckárováP.HulováD.MarekJ.DostálJ.SklenárV. (2003). Palmatine and berberine isolation artifacts. J. Nat. Prod. 66, 481–486. 10.1021/np0204996

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 213

  MartinezM. (1984). Las Plantas Medicinales De México, 3rd Edn. Mexico City: CIESAS, Cuadernos de la Casa Chata.

  • Google Scholar

• 214

  MartinezO. E. (1977). Flora de Veracruz, Fascículo 77. Riverside, CA: University of California.

  • Google Scholar

• 215

  MascarenoE.El-ShafeiM.MaulikN.SatoM.GuoY.DasD. K.et al. (2001). JAK/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion. Circulation104, 325–329. 10.1161/01.CIR.104.3.325

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 216

  MeenaA. K.BansalP.KumarS. (2009). Plants-herbal wealth as a potential source of ayurvedic drugs. Asian J. Tradit. Med. 4, 152–170.

  • Google Scholar

• 217

  MellC. D. (1929). Interesting sources of natural dyestuffs. Color51, 619–820.

  • Google Scholar

• 218

  MikageM.MouriC. (1999). Pharmacognostical studies of Berberis plants (Berberidaceae) from Nepal (1). Altitudinal, interspecific, and partial variations of berberine content in the barks. Sect. Title Pharm. 53, 249–254.

  • Google Scholar

• 219

  MillsS. (1985). The Dictionary of Modern Herbalism: A Comprehensive Guide to Practical Herbal Therapy. Wellingborough: Inner Traditions/Bear & Co.

  • Google Scholar

• 220

  MinaiyanM.GhannadiA.MahzouniP.Jaffari-ShiraziE. (2011). Comparative study of Berberis vulgaris fruit extract and berberine chloride effects on acetic acid-induced colitis in rats. Iran. J. Pharm. Res. 10, 97–104.

  • Pubmed Abstract
  • Google Scholar

• 221

  MisraP. S.BhakuniD. S.SharmaV. N.KaulK. N. (1961). Chemical constituents of Argemone mexicana. J. Sci. Ind. Res. 20, 186.

  • Google Scholar

• 222

  MoermanD. E. (1998). Native American Ethnobotany. Portland, OR: Timber Press.

  • Pubmed Abstract
  • Google Scholar

• 223

  MokgadiJ.TurnerC.TortoN. (2013). Pressurized hot water extraction of alkaloids in Goldenseal. Am. J. Anal. Chem. 4, 398–403. 10.4236/ajac.2013.48050

  • CrossRef
  • Google Scholar

• 224

  MølgaardP.HollerJ. G.AsarB.LibernaI.RosenbækL. B.JebjergC. P.et al. (2011). Antimicrobial evaluation of Huilliche plant medicine used to treat wounds. J. Ethnopharmacol. 138, 219–227. 10.1016/j.jep.2011.09.006

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 225

  Monforte-GonzalezM.CeciliaG. G.JorgeR. P.MildredC. P.Vazquez-FlotaF. (2012). Berberine and sanguinarine quantitation in Argemone mexicana L. (Papaveraceae) tissues by TLC-in situ fluorography. J. Planar Chromatogr. TLC24, 358–360. 10.1556/JPC.25.2012.4.14

  • CrossRef
  • Google Scholar

• 226

  MontesM.WilkomirskyT. (1987). Medicina Tradicional Chilena. Concepción: Editiorial de la Universidad de Concepción.

  • Google Scholar

• 227

  MuñozO. (2001). Plantas Medicinales de uso en Chile: Química y Farmacología. Editorial Universitaria.

  • Google Scholar

• 228

  MustafaA.TurnerC. (2011). Pressurized liquid extraction as a green approach in food and herbal plants extraction: a review. Anal. Chim. Acta703, 8–18. 10.1016/j.aca.2011.07.018

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 229

  MusumeciR.SpecialeA.CostanzoR.AnninoA.RagusaS.RapisardaA.et al. (2003). Berberis aetnensis C. Presl. extracts: antimicrobial properties and interaction with ciprofloxacin. Int. J. Antimicrob. Agents22, 48–53. 10.1016/S0924-8579(03)00085-2

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 230

  Musuyu MuganzaD.FruthB. I.Nzunzu LamiJMesiaG. K.KambuO. K.TonaG. L.et al. (2012). In vitro antiprotozoal and cytotoxic activity of 33 ethonopharmacologically selected medicinal plants from Democratic Republic of Congo. J. Ethnopharmacol. 141, 301–308. 10.1016/j.jep.2012.02.035

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 231

  NdenechoE. N. (2009). Herbalism and resources for the development of ethnopharmacology in Mount Cameroon region. Afr. J. Pharm. Pharmacol. 3, 78–86.

  • Google Scholar

• 232

  NeuwingerH. D. (1996). African Ethnobotany: Poisons and Drugs: Chemistry, Pharmacology, Toxicology. London: CRC Press.

  • Google Scholar

• 233

  Ngono NganeR.Koanga MogtomoM.Tchinda TiabouA.Magnifouet NanaH.Motso ChieffoP. R.Mballa BounouZ.et al. (2011). Ethnobotanical survey of some Cameroonian plants used for treatment of viral diseases. Afr. J. Plant Sci. 5, 15–21.

  • Google Scholar

• 234

  NguimatsiaF.BoustieJ.BarilF.AmorosM.GirreL. (1998). Les medicaments des pygmees Baka du Cameroun: moeurs therapeutiques, maladies et inventaire des plantes medicinales. Fitoterapia69, 29–40.

  • Google Scholar

• 235

  NoumiE. (2010). Ethno medicines used for treatment of prostatic disease in Foumban, Cameroon. Afr. J. Pharm. Pharmacol. 4, 793–805.

  • Google Scholar

• 236

  NoumiE.AnguessinB. (2010). Insecticides and ethnomedicine of HIV/AIDS at Tokombere (Far North Cameroon). Int. J. Pharm. Biomed. Sci.2, 20–28.

  • Google Scholar

• 237

  NoumiE.YumdinguetmunR. (2010). Plants and treatment of prostatic diseases in Foumban (West Region, Cameroon). Syllab. Rev.2, 9–16.

  • Google Scholar

• 238

  OdugbemiT. O.AkinsulireO. R.AibinuI. E.FabekuP. O. (2007). Medicinal plants useful for malaria therapy in Okeigbo, Ondo State, Southwest Nigeria. Afr. J. Tradit. Complement. Altern. Med. 4, 191–198.

  • Google Scholar

• 239

  OgbonnaD. N.SokariT. G.AgomuohA. A. (2008). Antimalarial activities of some selected traditional herbs from Southeastern Nigeria against Plasmodium species. Res. J. Parasitol. 3, 25–31. 10.3923/jp.2008.25.31

  • CrossRef
  • Google Scholar

• 240

  OhemuT. L.AgunuA.OlotuP. N.AjimaU.DafamD. G.AzilaJ. J. (2014). Ethnobotanical survey of medical plants used in the traditional treatment of viral infections in Jos, plateau state, Nigeria. Int. J. Med. Aromat. Plants4, 74–81.

  • Google Scholar

• 241

  OkunadeA. L.HuffordC. D.RichardsonM. D.PetersonJ. R.ClarA. M. (1994). Antimicrobial Properties of Alkaloids from Xanthorhiza simplicissima. J. Pharm. Sci. 83, 404–406. 10.1002/jps.2600830327

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 242

  OladunmoyeM. K.KehindeF. Y. (2011). Ethnobotanical survey of medicinal plants used in treating viral infections among Yoruba tribe of South Western Nigeria. Afr. J. Microbiol. Res.5, 2991–3004. 10.5897/AJMR10.004

  • CrossRef
  • Google Scholar

• 243

  OliverB. E. P. (1960). Medicinal Plants in Nigeria: Being a Course of Four Lectures. Pharmacy Department of the Nigerian College of Arts, Science and Technology, Ibadan.

  • Google Scholar

• 244

  OlowokudejoJ. D.KadiriA. B.TravihV. A. (2008). An ethnobotanical survey of herbal markets and medicinal plants in Lagos State of Nigeria. Ethnobot. Leafl. 2008, 116.

  • Google Scholar

• 245

  OnwuanibeR. C. (1979). The philosophy of African medical practice. Afr. Issues9, 25–28. 10.2307/1166259

  • CrossRef
  • Google Scholar

• 246

  OrhanI.SenerB.ChoudharyM. I.KhalidA. (2004). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some Turkish medicinal plants. J. Ethnopharmacol. 91, 57–60. 10.1016/j.jep.2003.11.016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 247

  OthmanM. S.SafwatG.AboulkhairM.Abdel MoneimA. E. (2014). The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats. Food Chem. Toxicol. 69, 175–181. 10.1016/j.fct.2014.04.012

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 248

  PakV. (2005). Medicine plants of folk medicine used for treatment of gastro-intestinal problems in Fergana valley. Korean Food Res. Inst. 18, 150–157.

  • Google Scholar

• 249

  PantN.GargH. S.BhakuniK. (1986). Chemical constituents of B. pseudoumbellata. Fitoterapia51, 427–428.

  • Google Scholar

• 250

  ParkD. W.JiangS.LiuY.SiegalG. P.InokiK.AbrahamE.et al. (2014). GSK3β-Dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury. Am. J. Physiol.307, L735–L745. 10.1152/ajplung.00165.2014

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 251

  ParkJ.-I.ShimJ.-K.DoJ.-W.KimS.-Y.SeoE.-K.KwonH.-J.et al. (1999). Immune-stimulating properties of polysaccharides from Phellodendri cortex (Hwangbek). Glycoconj. J. 16, 247–252. 10.1023/A:1007084506071

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 252

  ParsonsH. B. (1882). Examination of the root of Berberis aquifolium, v. alpens, “oregon grape root.”Pharm. J. 13, 46–48.

  • Google Scholar

• 253

  PatelM. C. (2013). Isolation of berberine from Berberis aristata by an acid dye method and optimization of parameters. Int. J. Pharm. Sci. Rev. Res. 20, 187–189.

  • Google Scholar

• 254

  PathakN. K. R.BiswasM.SethK. K.DwivediS. P. D.PandeyV. B. (1985). Chemical investigation of Argemone mexicana. Pharmazie40, 202.

  • Google Scholar

• 255

  PěnčíkováK.UrbanováJ.MusilP.TáborskáE.GregorováJ. (2011). Seasonal Variation of Bioactive Alkaloid Contents in Macleaya microcarpa (Maxim.) Fedde. Molecules16, 3391–3401. 10.3390/molecules16043391

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 256

  PerkinA. G.HummelJ. J. (1895). XLV.—The colouring principle of Toddalia aculeata and Evodia meliaefolia. J. Chem. Soc. Trans. 67, 413–416. 10.1039/CT8956700413

  • CrossRef
  • Google Scholar

• 257

  PesmanM. W. (1962). Meet Flora Mexicana. Globe, AZ: D.S. King.

  • Google Scholar

• 258

  PetcuP. (1965a). Der gehalt an alkaloiden und vitamin C in Berberis guimpelii. Planta Med. 13, 178–181. 10.1055/s-0028-1100108

  • CrossRef
  • Google Scholar

• 259

  PetcuP. (1965b). Phytochemical investigation of Berberis koreana. Farm. Bucharest, Rom. 13, 21–28.

  • Google Scholar

• 260

  PfozeN. L.MyrbohB.KumarY.RohmanR. (2014). Isolation of protoberberine alkaloids from stem bark of Mahonia manipurensis Takeda using RP-HPLC. J. Med. Plants Stud. 2, 48–57.

  • Google Scholar

• 261

  PhillipsR.FoyN. (1990). Herbs.London: Pan Books Ltd.

  • Google Scholar

• 262

  PhillipsR.RixM. (1991). PerennialsVol. 1 and 2. London: Pan Books Ltd.

  • Google Scholar

• 263

  PhillipsonJ. D.GrayA. I.AskariA. A. R.KhalilA. A. (1981). Alkaloids From Iraqi Species of Papaveraceae. J. Nat. Prod. 44, 296–307. 10.1021/np50015a011

  • CrossRef
  • Google Scholar

• 264

  PhondaniP. C.MaikhuriR. K.RawatL. S.FarooqueeN. A.KalaC. P.VishvakarmaS. C. R.et al. (2010). Ethnobotanical uses of plants among the Bhotiya tribal communities of Niti Valley in Central Himalaya, India. Ethnobot. Res. Appl. 8, 233–244. 10.17348/era.8.0.233-244

  • CrossRef
  • Google Scholar

• 265

  PilchW.SzygulaZ.TykaA. K.PalkaT.TykaA.CisonT.et al. (2014). Disturbances in pro-oxidant-antioxidant balance after passive body overheating and after exercise in elevated ambient temperatures in athletes and untrained men. PLoS ONE9:e85320. 10.1371/journal.pone.0085320

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 266

  RahalA.KumarA.SinghV.YadavB.TiwariR.ChakrabortyS.et al. (2014). Oxidative stress, prooxidants, and antioxidants: The interplay. Biomed Res. Int. (2014). 10.1155/2014/761264

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 267

  RajanS.SethuramanM. (1992). Mahonia leschenaultii–a toda plant. Anc. Sci. Life12, 242.

  • Pubmed Abstract
  • Google Scholar

• 268

  RajasekaranA.KumarN. (2009). Rasont – A traditional crude drug prepared from Berberis sp and its uses. Indian, J. Tradit. Knowl. 8, 562–563.

  • Google Scholar

• 269

  RansohoffR. M.HaflerD. A.LucchinettiC. F. (2015). Multiple sclerosis — a quiet revolution. Nat. Rev. Neurol. 11, 134–142. 10.1038/nrneurol.2015.14

  • CrossRef
  • Google Scholar

• 270

  RashidM. H.MalikM. N. (1972). Composition of alkaloids in some Berberis species. Pakistan J. For. 22, 43–47.

  • Google Scholar

• 271

  RashmiR. A.PokhriyalR.SinghY. (2009). Quantitative Estimation of Berberine in Roots of Different provenances of Berberis aristata DC by HPLC and Study of their Antifungal Properties. Pharmacogn. Mag. 5, 355–358. 10.4103/0973-1296.58566

  • CrossRef
  • Google Scholar

• 272

  RichertF. (1918). The extraction of berberine from “michai” (Berberis darwinii) and “calafate” (B. vuxifolia), in the Argentine. Rev. del Cent. Estud. Agron. y Vet. la Univ. Buenos Aires11, 11–13.

  • Google Scholar

• 273

  Ritch-KrcE. M.ThomasS.TurnerN. J.TowersG. H. N. (1996). Carrier herbal medicine: traditional and contemporary plant use. J. Ethnopharmacol. 52, 85–94. 10.1016/0378-8741(96)01392-X

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 274

  Rivera NúñezD.Obon de CastroC. (1996). Ethnopharmacology of Murcia, Actes du 2^aColloque Européen d'Ethnopharmacologei et de la 11^aConférence internationale d'Ethnomédecine (Heidelberg), 24.

  • Google Scholar

• 275

  RojsangaP.GritsanapanW. (2005). Variation of Berberine Content in Coscinium fenestratum Stem in Thailand Market. Mahidol Univ. J. Pharm. Sci. 32, 66–70.

  • Google Scholar

• 276

  RojsangaP.GritsanapanW.SuntornsukL. (2006). Determination of berberine content in the stem extracts of Coscinium fenestratum by TLC densitometry. Med. Princ. Pract. 15, 373–378. 10.1159/000094272

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 277

  SamalP. K. (2013). HPTLC analysis of berberine in Argemone mexicana, L. J. Glob. Trends Pharm. Sci. 4, 1073–1076.

  • Google Scholar

• 278

  SamhitaS. (1963). Sutrasthanam Lakshadi Group. Ed BhishagratnaK. K.. Varanasi: Chaukhamba Sanskrit Sansthan.

  • Google Scholar

• 279

  San MartínJ. (1983). Medicinal plants in central Chile. Econ. Bot. 37, 216–227. 10.1007/BF02858788

  • CrossRef
  • Google Scholar

• 280

  SandbergF. (1965). Etude sur les plantes medicinales et toxiques d'Afrique equatoriale. 1. Premier inventaire des plantes medicinales et toxiques de la region sudouest de la Republique Centrafricaine et de la region nord de la Republique du Congo/Brazzaville. Cah. la Maboké3, 5–49.

  • Google Scholar

• 281

  SantosA. C.AdkilenP. (1932). The alkaloids of Argemone mexicana. J. Am. Chem. Soc. 54, 2923–2924. 10.1021/ja01346a037

  • CrossRef
  • Google Scholar

• 282

  SantraD. K.SaojiA. N. (1971). Phytochemical study of Argemone mexicana latex. Curr. Sci. 40, 548–549.

  • Google Scholar

• 283

  SarafG.MitraA.KumarD.MukherjeeS.BasuA. (2010). Role of nonconventional remedies in rural India. Int. J. Pharm. Life Sci. 1, 141–159.

  • Google Scholar

• 284

  SasidharanS.ChenY.SaravananD.SundramK. M.Yoga LathaL. (2011). Extraction, isolation and characterization of bioactive compounds from plants' extracts. Afr. J. Tradit. Complement. Altern. Med. 8, 1–10.

  • Pubmed Abstract
  • Google Scholar

• 285

  SatiS. C.JoshiS. (2011). Aspects of antifungal potential of ethnobotanically known medicinal plants. Res. J. Med. Plants5, 377–391. 10.3923/rjmp.2011.377.391

  • CrossRef
  • Google Scholar

• 286

  SatijaS.BansalP.DurejaH.GargM. (2015). Microwave assisted extraction of Tinospora cordifolia and optimization through central composite design. J. Biol. Sci. 15, 106–115. 10.3923/jbs.2015.106.115

  • CrossRef
  • Google Scholar

• 287

  SatoF.YamadaY. (1984). High berberine-producing cultures of Coptis japonica cells. Phytochemistry23, 281–285. 10.1016/S0031-9422(00)80318-0

  • CrossRef
  • Google Scholar

• 288

  SatyavatiG. V.RainaM. K.SharmaM. (1987). Medicinal plants of India. New Delhi: Indian Council of Medical Research.

  • Google Scholar

• 289

  SchiefferG. W.PfeifferK. (2001). Pressurized liquid extraction and multiple, ultrasonically-assisted extraction of hydrastine and berberine from Goldenseal (Hydrastis canadensis) with susequent HPLC assay. J. Liq. Chromatogr. Relat. Technol. 24, 2415–2427. 10.1081/JLC-100105948

  • CrossRef
  • Google Scholar

• 290

  SchlotterbeckJ. O. (1902). Does Argemone mexicana contain morphine?J. Am. Chem. Soc. 24, 238–242. 10.1021/ja02017a006

  • CrossRef
  • Google Scholar

• 291

  SeinoY.FukushimaM.YabeD. (2010). GIP and GLP-1, the two incretin hormones: similarities and differences. J. Diabetes Investig. 1, 8–23. 10.1111/j.2040-1124.2010.00022.x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 292

  SenerB.TemizerH. (1988). Pharmacognosic investigations on Corydalis solida (L.) Swartz ssp. brachyloba (Boiss.) Cullen & Davis. II. Alkaloids of Corydalis solida (L.) Swartz ssp. brachyloba (Boiss.) Cullen & Davis. Gazi Univ. Eczac. Fak. Derg. 5, 9–11.

  • Google Scholar

• 293

  SenerB.TemizerH. (1990). Chemical Studies on the Alkaloids from Corydalis solida subsp. tauricola. Planta Med. 56, 510–510. 10.1055/s-2006-961052

  • CrossRef
  • Google Scholar

• 294

  SenerB.TemizerH. (1991). Chemical studies on the minor isoquinoline alkaloids from Corydalis solida subsp. brachyloba. J. Chem. Soc. Pakistan13, 63–66.

  • Google Scholar

• 295

  SezikE.YesiladaE.ShadidoyatovH.KuliveyZ.NigmatullaevA. M.AripovH. N.et al. (2004). Folk medicine in Uzbekistan: I. Toshkent, Djizzax, and Samarqand provinces. J. Ethnopharmacol. 92, 197–207. 10.1016/j.jep.2004.02.016

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 296

  ShahG. M.KhanM. A. (2006). Common medicinal folk recipes of Siran valley, Mansehra, Pakistan. Ethnobot. Leafl. 2006, 5.

  • Google Scholar

• 297

  ShahidM.RahimT.ShahzadA.LatifT. A.FatmaT.RashidM.et al. (2009). Ethnobotanical studies on Berberis aristata DC. root extracts. African, J. Biotechnol. 8, 556–563.

  • Google Scholar

• 298

  SharmaP. K.ChauhanN. S.LalB. (2005). Studies on plant associated indigenous knowledge among Malanis of Kullu district, Himachal Pradesh. Indian J. Trad. Knowl.4, 403–408.

  • Google Scholar

• 299

  ShigwanH.SaklaniA.HamrapurkarP. D.ManeT.BhattP. (2013). HPLC method development and validation for quantification of berberine from Berberis aristata and Berberis tinctoria. Int. J. Appl. Sci. Eng. 11, 203–211.

  • Google Scholar

• 300

  ShirwaikarA.ShirwaikarA.RajendranK.PunithaI. S. R. (2006). In vitro antioxidant studies on the benzyl tetra isoquinoline alkaloid berberine. Biol. Pharm. Bull. 29, 1906–1910. 10.1248/bpb.29.1906

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 301

  SinghA.DuggalS.KaurN.SinghJ. (2010). Berberine: Alkaloid with wide spectrum of pharmacological activities. J. Nat. Prod.3, 64–75.

  • Google Scholar

• 302

  SinghA.LalM.SamantS. S. (2009). Diversity, indigenous uses and conservation prioritization of medicinal plants in Lahaul valley, proposed Cold Desert Biosphere Reserve, India. Int. J. Biodivers. Sci. Manag. 5, 132–154. 10.1080/17451590903230249

  • CrossRef
  • Google Scholar

• 303

  SinghI. P.MahajanS. (2013). Berberine and its derivatives: a patent review (2009-2012). Expert Opin. Ther. Pat. 23, 215–231. 10.1517/13543776.2013.746314

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 304

  SinghJ.KakkarP. (2009). Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. J. Ethnopharmacol. 123, 22–26. 10.1016/j.jep.2009.02.038

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 305

  SinghR.KatiyarC.PasrijaA. (2010). Validated HPLC-UV method for the determination of berberine in raw herb Daruharidra (Berberis aristata DC), its extract, and in commercially marketed ayurvedic dosage forms. Int. J. Ayurveda Res. 1, 243. 10.4103/0974-7788.76789

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 306

  SinghR.TiwariS. S.SrivastavaS.RawatA. K. S. (2012). Botanical and phytochemical studies on roots of Berberis umbellata Wall. ex G. Don. Indian J. Nat. Prod. Resour. 3, 55–60.

  • Google Scholar

• 307

  SinghS. (2014). Quantitative analysis of Berberine in Argemone mexicana Linn. (Papaveraceae) using HPLC and HPTLC. Adv. Plant Sci. 27, 209–211.

  • Google Scholar

• 308

  SinghS. S.PandeyS. C.SrivastavaS.GuptaV. S.PatroB.GhoshA. C. (2003). Chemistry and medicinal properties of Tinospora cordifolia (Guduchi). Indian J. Pharmacol. 35, 83–91.

  • Google Scholar

• 309

  SirC. C.ChopraI. C. (1958). Indigenous Drugs of India. Kolkata: U.N.Dhar and Sons Private Limted.

  • Google Scholar

• 310

  SlavíkJ. (1978). Characterization of alkaloids from the roots of Papaver rhoeas L. Collect. Czechoslov. Chem. Commun. 43, 316–319. 10.1135/cccc19780316

  • CrossRef
  • Google Scholar

• 311

  SlavikJ.SlavikovaL. (1957). Alkaloide der mohngewächse (Papaveraceae) VIII. Die alkaloide des roten hornmohns (Glaucium corniculatum CURT.). Collect. Czechoslov. Chem. Commun. 22, 279–285. 10.1135/cccc19570279

  • CrossRef
  • Google Scholar

• 312

  SlavikJ.SlavikovaL. (1975). Alkaloids of Papaveraceae. LIX. Alkaloids from the leaves of Bocconia frutescens. Collect. Czechoslov. Chem. Commun. 40, 3206–3210. 10.1135/cccc19753206

  • CrossRef
  • Google Scholar

• 313

  SlavikJ.SlavikovaL.BochorakovaJ. (1989). Alkaloids of the Papaveraceae. Part LXXXVIII. Alkaloids from Papaver rhoeas var. chelidonioides O. Kuntze, P. confine Jord., and P. dubium L. Collect. Czechoslov. Chem. Commun. 54, 1118–1125. 10.1135/cccc19891118

  • CrossRef
  • Google Scholar

• 314

  SlavikovaL.SlavikJ. (1955). Alkaloids of Papaveraceae. VII. Argemone mexicana. Chem. List. Pro Vedu a Prum. 49, 1546–1549.

  • Google Scholar

• 315

  SlavikovaL.SlavikJ. (1966). Alkaloide der mohngewächse (Papaveraceae) XXXII. Über die alkaloide aus Hunnemannia fumariaefolia SWEET und über die konstitution des alkaloids HF 1. Collect. Czechoslov. Chem. Commun. 31, 1355–1362. 10.1135/cccc19661355

  • CrossRef
  • Google Scholar

• 316

  SlavikovaL.TschuS.SlavikJ. (1960). Alkaloids of Papaveraceae. XIV. Alkaloids of Argemone alba. Collect. Czechoslov. Chem. Commun. 25, 756–760. 10.1135/cccc19600756

  • CrossRef
  • Google Scholar

• 317

  SmythB. B. (1903). Preliminary list of medicinal and economic kansas plants, with their reputed therapeutic properties. Trans. Kansas Acad. Sci. 18, 191–209. 10.2307/3624794

  • CrossRef
  • Google Scholar

• 318

  SoodP.ModgilR.SoodM. (2010). Physico-chemical and nutritional evaluation of indigenous wild fruit Kasmal, Berberis lycium Royle. Indian J. Nat. Prod. Resour.1, 362–366.

  • Google Scholar

• 319

  SrinivasanG. V.UnnikrishnanK. P.Rema ShreeA. B.BalachandranI. (2008). HPLC estimation of berberine in Tinospora cordifolia and Tinospora sinensis. Indian J. Pharm. Sci. 70, 96–99. 10.4103/0250-474X.40341

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 320

  SrivastavaS. K.RaiV.SrivastavaM.RawatA. K. S.MehrotraS. (2006a). Estimation of heavy metals in different Berberis species and its market samples. Environ. Monit. Assess. 116, 315–320. 10.1007/s10661-006-7395-x

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 321

  SrivastavaS. K.RawatA. K. S.ManjooshaS.MehrotraS. (2006c). Pharmacognostic Evaluation of the Roots of Berberis chitria Lindl. Nat. Prod. Sci.12, 19–23.

  • Google Scholar

• 322

  SrivastavaS. K.RawatA. K. S.SrivastavaM. (2006b). Pharmacognostic evaluation of the roots of Berberis chitria. Nat. Prod. Sci. 12, 19–23.

  • Google Scholar

• 323

  SrivastavaS. K.SayyadaK.Singh RawatA. K.MehrotraS. (2001). Pharmacognostic evaluation of the root of Berberis aristata DC. Nat. Prod. Sci. 7, 102–106.

  • Google Scholar

• 324

  SrivastavaS. K.Singh RawatA. K.MehrotraS. (2004). Pharmacognostic evaluation of the root of Berberis asiatica. Pharm. Biol. 42, 467–473. 10.1080/13880200490886256

  • CrossRef
  • Google Scholar

• 325

  SrivastavaS. K.RawatA. K. S. (2007). Pharmacognostic evaluation of the roots of Berberis tinctoria Lesch. Nat. Prod. Sci. 13, 27–32.

  • Google Scholar

• 326

  SteffensP.NagakuraN.ZenkM. H. (1985). Purification and characterization of the berberine bridge enzyme from Berberis beaniana cell cultures. Phytochemistry24, 2577–2583. 10.1016/S0031-9422(00)80672-X

  • CrossRef
  • Google Scholar

• 327

  StermitzF. (1967). Alkaloids of the Papaveraceae. V. Muramine and berberine from Argemone squarrosa. J. Pharm. Sci. 55, 760–762. 10.1002/jps.2600560624

  • CrossRef
  • Google Scholar

• 328

  StermitzF. R.LorenzP.TawaraJ. N.ZenewiczL. A.LewisK. (2000). Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. Proc. Natl. Acad. Sci. U.S.A. 97, 1433–1437. 10.1073/pnas.030540597

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 329

  StermitzF. R.SharifiI. A. (1977). Alkaloids of Zanthoxylum monophyllum and Z. punctatum. Phytochemistry16, 2003–2006. 10.1016/0031-9422(77)80113-1

  • CrossRef
  • Google Scholar

• 330

  StermitzF. R.StermitzJ. R.ZanoniT. A.GillespieJ. (1974). Alkaloids of Argemone subintegrifolia and A. munita. Phytochemistry13, 1151–1153. 10.1016/0031-9422(74)80089-0

  • CrossRef
  • Google Scholar

• 331

  StuartG. A.SmithF. P. (1977). Chinese Materia Medica: Vegetable Kingdom. Shanghai: Gordon Press Publishers.

  • Google Scholar

• 332

  TaborskaE.FrantisekV.SlavikJ. (1980). Alkaloids of the Papaveraceae. LXXI. Alkaloids from Bocconia frutescens L. Collect. Czechoslov. Chem. Commun. 45, 1301–1304. 10.1135/cccc19801301

  • CrossRef
  • Google Scholar

• 333

  TadzhibaevM. M.ZatorskayaI. N.LutfullinK. L.ShakirovT. T. (1974). Isolation of berberine. Khimiya Prir. Soedin. 10, 48–50. 10.1007/BF00568218

  • CrossRef
  • Google Scholar

• 334

  TanE.LuoS.LinS.TanR.YuW.YiZ.et al. (2013). Determination of five active ingredient in Phellodendron chinensis var. glabiusculum and P. chinense by HPLC. Zhongguo Shiyan Fangjixue Zazhi19, 135–139.

  • Google Scholar

• 335

  TangJ.FengY.TsaoS.WangN.CurtainR.WangY. (2009). Berberine and Coptidis Rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J. Ethnopharmacol. 126, 5–17. 10.1016/j.jep.2009.08.009

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 336

  TangW.EisenbrandG. (1992). Corydalis turtschaninovii Bess. f. yanhusuo YH Chou et CC Hsü, in Chinese Drugs of Plant Origin (Berlin; Heidelberg: Springer), 377–393.

  • Google Scholar

• 337

  TantaquidgeonG. (1928). Mohegan medicinal practices, weather-lore and superstitions. SI-BAE Annu. Rep.43, 264–270.

  • Google Scholar

• 338

  TengH.ChoiO. (2013). Optimum extraction of bioactive alkaloid compounds from Rhizome coptidis (Coptis chinensis Franch.) using response surface methodology. Solvent Extr. Res. Dev. 20, 91–104. 10.15261/serdj.20.91

  • CrossRef
  • Google Scholar

• 339

  ThirupurasundariC. J.PadminiR.DevarajS. N. (2009). Effect of berberine on the antioxidant status, ultrastructural modifications and protein bound carbohydrates in azoxymethane-induced colon cancer in rats. Chem. Biol. Interact. 177, 190–195. 10.1016/j.cbi.2008.09.027

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 340

  TiwariK. P.MasoodM. (1979). Chemical constituents of Berberis coriaria Royle. J. Indian Chem. Soc. 56, 310–311.

  • Google Scholar

• 341

  TiwaryJ. K.BallabhaR.TiwariP. (2010). Ethnopaediatrics in Garhwal Himalaya. Uttarakhand, India (Psychomedicine Medice). NY Sci. J. 3, 123–126.

  • Google Scholar

• 342

  TomèF.ColomboM. L. (1995). Distribution of alkaloids in Chelidonium majus and factors affecting their accumulation. Phytochemistry40, 37–39. 10.1016/0031-9422(95)00055-C

  • CrossRef
  • Google Scholar

• 343

  TomitaM.KugoT. (1956). Alkaloids of Berberidaceous plants - XIX: Alkaloids of B. tschonoskyana I. Isolation of bases. Yakugak Zasshi79, 317–321. 10.1248/yakushi1947.79.3_317

  • CrossRef
  • Google Scholar

• 344

  TorresR.VillarroelL.UrzuaA.FajardoV. (1992). Constituents of Berberis congestiflora and Berberis horrida. Fitoterapia63:376.

  • Google Scholar

• 345

  TsabangN.FokouP. V. T.TchokouahaL. R. Y.NoguemB.Bakarnga-ViaI.NguepiM. S. D.et al. (2012). Ethnopharmacological survey of Annonaceae medicinal plants used to treat malaria in four areas of Cameroon. J. Ethnopharmacol. 139, 171–180. 10.1016/j.jep.2011.10.035

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 346

  UchiyamaT.KamikawaH.OgitaZ. (1989). Anti-ulcer effect of extract from Phellodendri cortex. Yakugaku zasshi J. Pharm. Soc. Japan109, 672–676. 10.1248/yakushi1947.109.9_672

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 347

  ul HaqI.HussainM. (1993). Medicinal plants of Mansehra. Hamdard Med.36, 63–100.

  • Google Scholar

• 348

  UniyalS. K.SinghK. N.JamwalP.LalB. (2006). Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. J. Ethnobiol. Ethnomed. 2:14. 10.1186/1746-4269-2-14

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 349

  UphofJ. C. (1959). Dictionary of Economic Plants, 2nd edn. Lehre.

  • Google Scholar

• 350

  UpretyY.AsselinH.BoonE. K.YadavS.ShresthaK. K. (2010). Indigenous use and bio-efficacy of medicinal plants in the Rasuwa District, Central Nepal. J. Ethnobiol. Ethnomed. 6:3. 10.1186/1746-4269-6-3

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 351

  UrzúaA.TorresR.VillarroelL.FajardoV. (1984). Secondary metabolites of Berberis darwinii. Rev. Latinoam. Quim. 15, 27–29.

  • Google Scholar

• 352

  UsherG. (1974). A Dictionary of Plants Used by Man. London: Constable and Company Ltd.

  • Google Scholar

• 353

  VennerstromJ. L.KlaymanD. L. (1988). Protoberberine alkaloids as antimalarials. J. Med. Chem. 31, 1084–1087. 10.1021/jm00401a006

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 354

  VennerstromJ. L.LovelaceJ. K.WaitsV. B.HansonW. L.KlaymanD. L. (1990). Berberine derivatives as antileishmanial drugs. Antimicrob. Agents Chemother. 34, 918–921. 10.1128/AAC.34.5.918

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 355

  VersteeghC. P. C.SosefM. S. M. (2007). Revision of the African genus Annickia (Annonaceae). Syst. Geogr. Plants77, 91–118.

  • Google Scholar

• 356

  VuddandaP. R.ChakrabortyS.SinghS. (2010). Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin. Investig. Drugs19, 1297–1307. 10.1517/13543784.2010.517745

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 357

  WangC.LiJ.LvX.ZhangM.SongY.ChenL.et al. (2009). Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur. J. Pharmacol. 620, 131–137. 10.1016/j.ejphar.2009.07.027

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 358

  WangW.ShenQ.LiangH.HuaC.LiuY.LiF.et al. (2016). Pharmacokinetic studies of novel berberine derivatives with ultra-performance liquid chromatography–tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1031, 172–180. 10.1016/j.jchromb.2016.07.038

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 359

  WangY.YiX.GhanamK.ZhangS.ZhaoT.ZhuX. (2014). Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption. Metabolism63, 1167–1177. 10.1016/j.metabol.2014.05.013

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 360

  WattG. (1883). Economic Products of India, Calcutta International Exhibition. Calcuta: Medicinal Products, Superintendent of Government Print.

  • Google Scholar

• 361

  WeinerM. A. (1980). Earth Medicine-Earth Food: Plant Remedies, Drugs, and Natural Foods of the North American Indians. New York, NY: Macmillan.

  • Google Scholar

• 362

  WillamanJ. J.SchubertB. G. (1961). Alkaloid-Bearing Plants and Their Contained Alkaloids (No. 1234). Agricultural Research Service, US Department of Agriculture.

  • Google Scholar

• 363

  WuX.LiY.WangQ.LiW.FengY. (2015). Effects of berberine and pomegranate seed oil on plasma phospholipid metabolites associated with risks of type 2 diabetes mellitus by U-HPLC/Q-TOF-MS. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1007, 110–120. 10.1016/j.jchromb.2015.11.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 364

  XiJ. (2015). Ultrahigh pressure extraction of bioactive compounds from plants-a review. Crit. Rev. Food Sci. Nutr. 57, 1097–1106. 10.1080/10408398.2013.874327

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 365

  XiaX.YanJ.ShenY.TangK.YinJ.ZhangY.et al. (2011). Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS ONE6:e16556. 10.1371/journal.pone.0016556

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 366

  XiaoH. B.SunZ. L.ZhangH. B.ZhangD. S. (2012). Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation. Pharmacol. Rep.64, 889–895. 10.1016/S1734-1140(12)70883-6

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 367

  XiaoL.XuN.GuoM.GuoM.LvBTaoH.et al. (2014). Berberine protects endothelial progenitor cell from damage of TNF-alpha via the PI3K/AKT/eNOS signaling pathway. Eur. J. Pharmacol. 743, 11–16. 10.1016/j.ejphar.2014.09.024

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 368

  XuB.LiP.ZhangG. (2015). Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignmen. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 988, 33–44. 10.1016/j.jchromb.2015.01.039

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 369

  XuK.HeG.QinJ.ChengX.HeH.ZhangD.et al. (2017). High-efficient extraction of principal medicinal components from fresh Phellodendron bark (Cortex phellodendri). Saudi J. Biol. Sci. 25, 811–815. 10.1016/j.sjbs.2017.10.008

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 370

  YangL.MengX.YuX.KuangH. (2017). Simultaneous determination of anemoside B4, phellodendrine, berberine, palmatine, obakunone, esculin, esculetin in rat plasma by UPLC-ESI-MS/MS and its application to a comparative pharmacokinetic study in normal and ulcerative colitis rats. J. Pharm. Biomed. Anal. 134, 43–52. 10.1016/j.jpba.2016.11.021

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 371

  YangT.-H. (1960a). Alkaloids of Berberidaceae. XXIX. Alkaloids of Mahonia lomariifolia and M. morrisonensis. Yakugaku Zasshi80, 1304–1307. 10.1248/yakushi1947.80.9_1304

  • CrossRef
  • Google Scholar

• 372

  YangT.-H. (1960b). Alkaloids of Berberidaceae. XXVIII. Alkaloids of Berberis morrisonensis. Yakugaku Zasshi80, 1302–1304. 10.1248/yakushi1947.80.9_1302

  • CrossRef
  • Google Scholar

• 373

  YangT.-H.LuS.-T. (1960a). Alkaloids of berberidaceous plants. XXV. Alkaloids of Berberis kawakamii. 1. Yakugaku Zasshi80, 847–849. 10.1248/yakushi1947.80.6_847

  • CrossRef
  • Google Scholar

• 374

  YangT.-H.LuS.-T. (1960b). Alkaloids of berberidaceous plants. XXVI. Alkaloids of Berberis mingetsensis. 1. Yakugaku Zasshi80, 849–851. 10.1248/yakushi1947.80.6_849

  • CrossRef
  • Google Scholar

• 375

  YavichP. A.KakhtelidzeM. B.SarabunovichA. G. (1993). Quantitative determination of berberine in Phellodendron lavallei bark. Farmatsiya42, 49–50.

  • Google Scholar

• 376

  YeungH. (1985). Handbook of Chinese Herbs and Formulas, Vol. 1.Los Angeles, CA: Institute of Chinese Medicine.

  • Google Scholar

• 377

  YinJ.GaoZ.LiuD.LiuZ.YeJ. (2008a). Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab. 294, E148–E156. 10.1152/ajpendo.00211.2007

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 378

  YinJ.XingH.YeJ. (2008b). Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism57, 712–717. 10.1016/j.metabol.2008.01.013

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 379

  YogeshH. S.ChandrashekharV. M.KattiH. R.GanapatyS.RaghavendraH. L.GowdaG. K.et al. (2011). Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in ovariectomized rats. J. Ethnopharmacol. 134, 334–338. 10.1016/j.jep.2010.12.013

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 380

  YooS. J.LeeK. B.KwakJ. H. (1986). Studies on the seasonal variation of berberine contents in Berberis koreana. Saengyak Hakhoechi17, 123–128.

  • Google Scholar

• 381

  YuC.TanS.ZhouC.ZhuC.KangX.LiuS.et al. (2016). Berberine reduces uremia-associated intestinal mucosal barrier damage. Biol. Pharm. Bull. 39, 1787–1792. 10.1248/bpb.b16-00280

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 382

  ZabihullahQ.RashidA.AkhtarN. (2006). Ethnobotanical survey in kot Manzaray Baba valley Malakand agency, Pakistan. Pak. J. Plant Sci.12, 115–121.

  • Google Scholar

• 383

  ZahaV. G.QiD.SuK. N.PalmeriM.LeeH. Y.HuX.et al. (2016). AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. J. Mol. Cell. Cardiol. 91, 104–113. 10.1016/j.yjmcc.2015.12.032

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 384

  ZamanM. B.KhanM. S. (1970). Hundred drug plants of West Pakistan. Medicinal Plant Branch of Pakistan Forest Institute.

  • Google Scholar

• 385

  ZengX. (1999). Relationship between the clinical effects of berberine on severe congestive heart failure and its concentration in plasma studied by HPLC. Biomed. Chromatogr.13, 442–444. 10.1002/(SICI)1099-0801(199911)13:7<442::AID-BMC908>3.0.CO;2-A

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 386

  ZhangJ.CaiC. T.CaiZ. Q.LiuG. Z.LuoY.YangZ. X. (2008). Variation patterns of Coptis teeta biomass and its major active compounds along an altitude gradient. J. Appl. Ecol. 19, 1455–1461.

  • Pubmed Abstract
  • Google Scholar

• 387

  ZhaoX.ZhangJ.TongN.ChenY.LuoY. (2012). Protective effects of berberine on Doxorubicin-induced hepatotoxicity in mice. Biol. Pharm. Bull. 35, 796–800. 10.1248/bpb.35.796

  • Pubmed Abstract
  • CrossRef
  • Google Scholar

• 388

  Zovko KoncićZ.KremerD.KarlovćK.KosalecI. (2010). Evaluation of antioxidant activities and phenolic content of Berberis vulgaris L. and Berberis croatica Horvat. Food Chem. Toxicol. 48, 2176–2180. 10.1016/j.fct.2010.05.025

  • Pubmed Abstract
  • CrossRef
  • Google Scholar