Ethnomedicinal values of Boerhaavia diffusa L. as a panacea against multiple human ailments: a state of art review

Ethnopharmacological relevance: Therapeutic botanicals (plants and derivatives) are in use since antiquity for various health ailments. The ethnic community is the repository of the information, the multifactorial therapeutic applications of which may often need scientific validation. The spreading hogweed or Boerhaavia diffusa L., also known as Punarnava, is a reassuring medicinal herb with diverse pharmacological benefits. It is used in Ayurveda in Asia and Africa as a rejuvenator or “Rasayan” for its excellent antiaging and antioxidant properties. Aim: The study aimed at compiling the state-of-art knowledge of the medicinal benefits of Boerhaavia diffusa L. and unraveling the unexplored commercially useful bioactive constituents by establishing their possible pharmacological benefits. Methods: The data from published literature, confined to pharmacological manifestations of various phytocomponents of Boerhaavia diffusa L. or its parts like root, leaf and stem were extracted from scientific databases, Google, Science Direct, PubMed, etc. using its antifungal, antibacterial, anticancer, anti-inflammatory, antidiabetic, hepatoprotective, cardioprotective, renoprotective, antifertility benefits and molecular docking study as search strings and keywords. Further, the reported in silico studies for bioactivity and bioavailability are detailed. Results: The botanicals possess numerous bioactive compounds, the most widely reported ones being phenolic (punarnavoside, trans-caftaric acid, boerhavic acid), rotenoid (boeravinones A-J), flavonoid (borhaavone, quercetin, kaempferol), isoflavonoid (2′-O-methyl abronisoflavone), alkaloid (punarnavine), steroid (boerhavisterol, β-Ecdysone), anthracenes and lignans (liriodendrin, syringaresinol mono-β-D-glucoside). Some of the reported reassuring benefits of their purified forms or even the crude extracts are antidiabetic, antimicrobial, anticancer, antioxidant, anti-inflammatory, hepatoprotective, renoprotective, cardioprotective, antifertility, etc. Conclusion: The article provides an extensive study on such pharmacological utility to support the ethnomedicinal use of Boerhaavia diffusa L. and propose possible mechanism of the various bioactive compounds in optimising metabolic dysfunctions, healing and protecting vital body organs, often related to the magnificent antioxidant property of this ayurvedic panacea. Further, establishing specific roles of its yet-to-explore bioactive constituents for diverse pharmacological applications is suggested.


Introduction
Boerhaavia diffusa L. (BD) of family Nyctaginaceae, commonly known as spreading hogweed, is a perennial, prostrate herb with pink flowers and sticky fruits (Figure 1).Popularly called Punarnava, it means renewer or rejuvenator of body because of its anti-aging property (Wahi et al., 1997).Its old root stock remains dormant during summer and regenerates during the rain.The various parts of Punarnava are rich in diverse bioactive compounds and are extensively used as a "rasayan" for its exceptional properties like immunity boosting, reestablishing youthfulness, and strengthening the body and mind (Samhita and Varanasi, 1998).Oxidative stress (due to an imbalance between the reactive oxygen species or oxidants production and their utilisation) often leads to diseases like dementia, Alzheimer's disease, Parkinson's disease, heart attack, myocardial infarction and other gerontological ailments (Demopoulos et al., 1980;Cadet, 1998).Promising antioxidant property of the BD parts makes it special for pharmacological applications (Das et al., 2022).Both the root and the shoot systems of this wonder plant are rich primarily in phenolics (punarnavoside, trans-caftaric acid and boerhavic acid), rotenoids (boeravinones A-J), flavonoids (borhaavone, quercetin, kaempferol), isoflavonoids (2′-O-methyl abronisoflavone), alkaloids (punarnavine), steroids (boerhavisterol, β-Ecdysone), anthracenes and lignans (liriodendrin, syringaresinol mono-β-D-glucoside) and many fatty acids and proteins contributing to its incredible biotherapeutic potential (Gaur et al., 2022).Its antidiabetic, antimicrobial and other similar bioactivities of BD is extensively studied, reviewed and are reported often.
Although, historically and ethnomedicinally the plant has been associated among especially the Asian and African ethnic population both as a food as well as an ayurvedic intervention, however the transition into the modern civilisation and the medical sciences is yet to realise its potential.The wellbeing benefits of BD are so much more everencompassing and reassuring that, considering it as a panacea against an array of modern day diseases shall not be an overstatement.In light of this, extensive research and both vertical (deeper insights into the heather to unknown medicinal benefits) as well as horizontal (spread of the medicinal benefits in the global population across ethnicity and race defying the geographical barriers) understandings shall benefit the humanity in general and the ethnic population in particular.
This article attempts to compile the advances on the therapeutic role of BD for multiple human health benefits including in metabolic disorders, vital organ protection, antimicrobial, anticancer, antiinflammatory and healing properties against various diseases especially in the last decade (2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022)(2023), to validate and support its ethnomedicinal utility.It attempts also to reorients and synthesise all its pharmacological aspects, the possible relationship between phytocompounds, the bioactivities, and the probable mechanism of action in blood sugar management.BD is an incredible herbal remedy containing an array of pharmaceutically active chemical components.
BD has free radicals scavenging and glutathione content increasing antioxidants that help treat hepatitis and hepatic cirrhosis.BD leaf is a source of significant quantity of flavonoid glycoside moiety with high eupalitin-3-O-D-galactopyranoside (yellow powder crystal) yield.Silymarin, a flavonoid glycoside structurally similar to eupalitin-3-O-D-galactopyranoside was the only known natural stuff used for hepatoprotection till late.Human hepatoma cell lines are proposed as an alternative to human hepatocytes for in vitro modeling of normal liver cells.HepG2 hepatoma cell line is widely used in liver function, metabolism and drug toxicity research.The biochemical and morphological properties of these cells being similar to normal hepatocytes, they are used in studies that determine the hepatoprotective properties of medicinal plants.

Materials and methods
Relevant research and review articles were considered, and the mentioned aspects were collected and compiled.Extensive literature search on the medicinal, antimicrobial and pharmacological properties of the whole plant or the parts of BD was conducted using specialised and dedicated search engines and websites like Google Scholar, PubMed, ScienceDirect, EBSCO, Sci-Hub, SciFinder, etc. Major thrust was on the literature that covered the antibacterial, antifungal, anticancer, anti-inflammatory, hepatoprotective, cardioprotective, renoprotective, antidiabetic, antifertility characteristics of BD or its parts (like root, leave, stem, etc.) and molecular docking study as keywords.

Ethnomedicinal usage
With cooling effect and bitter taste, BD is used since ages to treat various ailments.It rejuvenates the whole body enhancing the vigour and vitality upon its routine use justifying its Indian name Punarnava.It has emetic, expectorant, diaphoretic, stomachic, laxative and diuretic properties (Nadkarni, 1976).Due to its multifarious therapeutic potential against abdominal pain, diarrhoea, epilepsy, dysentery, urinary and kidney complications, jaundice, anemia, pneumonia, splenomegaly, etc., it is extensively used globally as a rejuvenator in various medicinal formulations, especially in Asia, Africa and Latin America.It is a well-known tonic, blood purifier and a uterine bleeding preventer to check postpartum heamorrhage.Also, it is useful in wound healing and skin ailments like itching and eczema (Agrawal et al., 2011).It improves digestion, maintains healthy body mass index, prevents anaemia, hernia and respiratory distress.Its root extract is a potential kidney, heart and liver stimulant.It protects dilapidated kidneys in the diabetic.Due to its diuretic, renoprotective and laxative properties, it is useful in treating asthma, constipation, cough and detoxifying body.It is reported to be used against dropsy, ascites, gonorrohea, swelling of legs, intestinal worm infestation, jaundice and other hepatic complications.It relieves from inflammation and joint pains, boosts immunity and strengthens the lungs.Its root paste may be used as a miraculous dressing for ulcers and swellings.It is very much beneficial in nerve flaws and paralysis, in treating fever and a loss of appetite (Bhowmik et al., 2012).In case of ascites, liver cirrhosis is normally followed by congestive heart failure.Here herbal diuretics are preferred to correct abnormal fluid dynamics in the body.Having anti-inflammatory property, the whole leaf or its formulation is taken orally or applied locally for wound-healing or to detoxify from scorpion sting and snake bites (Mishra et al., 2014).

Pharmacological properties of BD
Different BD parts like root, leaf, flower, fruit and seed are frequently employed to treat various ailments, either on their own or as a bioactive component in medicinal formulations (Rao, 2016).Distinct BD parts have diverse phytochemical compositions with diversified therapeutic benefits.Thoroughly analysed literature from databases agrees that BD and its parts pose numerous bioactive large variety (quality) and amount (quantity) of phytocompounds (Figure 1).The leaves are utilised as a leafy vegetable by Odias in India owing to the superior nutraceutical aspects, high on protein, fatty acid, vitamin C and B complex and calcium.Figure 1 highlights the active substances in BD leaves and the notable bioactivities.Owing to its numerous bioactivities including as antibacterial, antidiabetic, antioxidant, anticancer, hepatoprotective, renoprotective, cardioprotective, diuretic, anti-inflammatory, and immunomodulatory characteristics, in-depth research has been performed on BD (Figure 2).Several studies conducted globally on this wonder herb correlated the diverse phytocompounds and the bioactive potentials.All the reports are classified under five categories of bioactivity, i.e., metabolic disorders, antimicrobial activities, antiinflammatory and healing properties, anticancer property and major organ protective role of different compounds extracted from BD of its parts for better understanding and ease of citation.The extracts and isolated phytocompounds of BD studied in vivo, ex vivo and in vitro in the last decade between 2013 and 2023 are compiled and presented in Table 1 through 5

Protective role against metabolic disorders
Globally, 422 million people suffered from diabetes as per the global reports on diabetes by the World Health Organisation (WHO), 2023.Three out of every four diabetic belonged to younger age groups primarily in the under-developed and developing economies greatly impairing their productivity and productive years of life.Nearly 1.5 million diabetic die each year due to hyperglycaemia related complications.The diabetic is also prone to infectious diseases like TB (tuberculosis), malaria and HIV/AIDS.As the cases are rising alarmingly, diabetes is becoming a global challenge.With increasing number of diabetics in the present era majorly due to sedentary lifestyle, anomalous food habits, stress, etc., India is becoming the "diabetic hub".
The compared antidiabetic potential of root, stem and leaf extracts of BD to standard over-the-counter drugs in streptozotocin-induced diabetic animal models significantly reduced blood glucose level, downregulated oxidative stress markers and showed free radicals scavenging ability (Montefusco-Pereira et al., 2013;Alam et al., 2018;Vasundhara and Devi, 2018).Ethanol-based leaf-extract (500 mg/kg, 45 days) altered carbohydrate metabolising enzymes considerably to near normal in Streptozotocin (STZ) (60 mg/kg I.P.) mediated diabetic rat (Vasundhara and Devi, 2018), validating its antidiabetic effect.Significantly reduced liver glycogen content in diabetic rat was restored with leaf-extract treatment, mediated through inhibited jejunal glucose uptake and augmented glucose uptake by skeletal muscle (Oyebode et al., 2018).Increased liver enzymes (ALP, SGPT, and SGOT) levels in plasma upon being released from liver cytosol  into the bloodstream in STZ-induced diabetic rat confirmed liver necrosis.The methanol extract completely reversed this clinical condition in test rats.Elevated glucose levels in diabetic rats due to oxidative stress that inactivated antioxidant enzymes like SOD, CAT, and GPx possibly through glycation was stabilised by administering methanol-based BD extract (Alam et al., 2018).Elevated renal and hepatic marker levels in STZ-induced diabetic rat was normalised after treating with ethanol-based leaf-extract of BD (Vasundhara and Devi, 2018).Most of the therapeutic manifestations of BD are attributed to its incredible antioxidant properties (Das et al., 2022).Metabolic disorders often increase due to an imbalance in oxidative status.A compilation of the prophylactic role of BD reported in the last decade is presented in Table 1.The reported possible modes of action of it as an antidiabetic as proposed by various researchers are compiled in Figure 3.

Antimicrobial activities of BD
The extracts of root, stem and leaf parts of BD have demonstrated their antimicrobial properties.Higher (200 and 100 mg/mL) doses of root extract inhibited S. aureus better with a 12-16 mm zone of inhibition, whereas the leaf extract showed similar result of 11-13 mm zone of inhibition even at lower (50 and 25 mg/mL) doses.While root extract was effective against S. typhi also, none was effective against E. coli (Majgaine and Verma, 2017), contradicting the findings of few other researchers.The antiplasmodial effectiveness was examined on Plasmodium berghei NK 65, a chloroquine-resistant strain, using suppressive, curative and preventive malaria male and female albino mice models.The extract exhibited the best antipyretic effect at 125 mg/kg by the third day in suppressive models confirming its antimalarial activity.The extract reduced the plasma Ca 2+ levels better at 500 mg/kg than the nifedipine (positive control) treated at 1.043 vs. 1.35 mmol/L.Its efficacy in reducing malaria-induced pyrexia by blocking Ca 2+ channel in the erythrocytes validates its ethnic use as an antimalarial (Adefokun et al., 2015).The evaluated antileishmanial activity of BD and OS on L. donovani infected BALB/c mice model had the maximum parasite clearance at 5day BD:OS:100:400 mg/kg combination therapy.It also upregulated cell-mediated immunity with increased delayed hypersensitivity and enhanced immunoglobulin G2a (IgG2a) production.The extract normalised abnormally high serum urea, blood urea nitrogen (BUN), creatinine, glutamic oxaloacetate transaminase and glutamic pyruvate transaminase levels (Kaur et al., 2015).Reports on antibacterial, antihelminthic and antimalarial activities of BD published between 2013 and 2023 are compiled and presented in Table 2.

Anti-inflammatory, anti-cataract and wound-healing properties of BD
Methanol extract of BD leaf reportedly had promising antioxidant and anti-inflammatory activity due to high polyphenolics content.Inflammatory mediators like leukotrienes (LTs) are generated in body via 5-LOX pathway.Polyphenolics, flavonoids, saponin, etc.As antioxidants reportedly exhibited antilipoxygenase activities possibly by blocking arachidonic acid pathway and serving as free radicals scavengers (Ibrahima et al., 2018).BD is reported to have significant anti-inflammatory, anticataract, wound and gastric ulcer healing traits (Table 3).Antioxidant defense mechanism by reducing ROS production and inflammation is schematically presented in Figure 4.

Anticancer and anti-proliferative properties of BD
The oncoprotective and chemopreventive properties of phytocompounds from BD are reported by many, often due to the antioxidant properties.Alcohol and water-based extracts could contain several biocompounds like punarnavine, punarnavosides, rotenoids, reducing sugars, starch, and lignans, liriodendrin, syrigaresinol and several boeravinones (boeravinone A-J) (Das et al., 2022).Boeravinones G and H reportedly inhibited drug efflux potency of BCRP/ABCG2, the breast cancer resistance protein, a multidrug transporter that induces chemotherapy resistance in cancer cell (Ahmed-Belkacem et al., 2007).As BD reportedly controls unregulated cell growth through S phase inhibition and apoptosis, its cytotoxic activity was effective against many tested cancer cell lines proving its claimed anticancer activity.Relevant reports published between 2013 and 2023 are presented in Table 4.

Organ protective role of BD
The whole BD is popular among ethnic community for its excellent healing properties against diseases which is time-and-again validated through scientific investigations for the proclaimed ethnopharmacological properties.Vital organs of human body such as heart (Figure 5), liver and kidney are protected by the phytocomponents safeguarding them.The various reports pertinent to the major organ protective roles of BD published in the last decade are compiled and presented in Table 5.

Bioinformatics approaches to decode the benefits
Crude BD extract is highly effective and traditionally used against mastitis caused by S. aureus.The antimastitis activity of the phytochemicals in BD was examined in silico by Sruthy et al. ( 2018) through docking analysis.Based on ADMET properties, 20 BD phytochemicals were selected for docking.Boeravinone A, B, C, D, E, and F had good docking scores and interacted better with the active sites of the target receptor protein of S. aureus.This study helped design novel drugs to treat mastitis.Similarly, Kaviya et al. (2022) analysed the hot and cold solvent extracted BD phytochemicals from leaves, stems and roots, and found that ethanolic root extract demonstrated clear zones of inhibition for P. aeruginosa (8 mm) and S. aureus (20 mm) at 200 µg concentration.Molecular docking of 2-(1,2 dihydroxyethyl)-5-{[2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydrochromen-6-yl]oxy}oxolane-3,4-diol exhibited minimal binding score against P. aeruginosa.Patients with nephrotic syndrome are resistant to steroid and immunosuppressive treatments.Many natural compounds are traditionally used to treat chronic diseases.Sahu et al. (2022a) screened the potency of 66 bioactive compounds phytochemicals Frontiers in Chemistry frontiersin.org11 Das et al. 10.3389/fchem.2023.1297300 in BD against mutant nephrin protein, against wild and mutant Ig4 domain of nephrin protein through AutoDock raccoon.Simulated molecular dynamics in 100 ns trajectory of Ig4 domain of nephrin protein with Boeravinone M and Boeravinone E showed that the latter's binding increased the compactness, effectively modulating the stability and function.Sahu et al. (2022b) extensively investigated the anticancer properties of BD phytochemicals Boeravinone A, B, C, D, E, F, G, H, I, and J.While analysing binding efficacy and free energy landscape of both the native and mutant CDK2AP1 protein with these by molecular docking, Boeravinone J showed the best binding affinity (−7.9 kcal/mol) towards native CDKAP1.MD simulation for 100 ns suggested that H23R mutant-Boeravinone J complex had the minimum structural changes with less conformational mobility compared to C105A mutant.Such study can help develop Boeravinone E therapeutics.

FIGURE 4
The DNA damage mechanism due to oxidative stress and the role of boeravin in its repair.
and favoured efficient docking and protease inhibition.The druglikeness property of Bioquercetin, Biorobin, and Boeravisterol was ADME analysed, and Boeravisterol was the most suitable that obeyed the Lipinsky's rule.Comparative docking of these carried out also against MERS Mpro showed that the obtained binding energies were unfavourable.

Toxicity studies and clinical trials
Because of the age-old tried and tested use with no known sideeffect, traditional herbs and their products are often considered as safe as ethnomedicines.However, few toxicity studies on BD extracts have been reported to empirically verify and validate this perception.Karwasra et al. (2016) observed no adverse effect level in BD root extract even at 1,000 mg/kg in Wistar rats.Orisakwe et al. (2003) studied the acute and subchronic toxicity of BD leaf at 500, 1,000, and 2,000 mg/kg aqueous extract in albino mice and rats, and the lethal dose (LD 50 ) for both was more than 2,000 mg/kg (p.o.).With increased food and fluid intake, the rats treated with the extract had a progressive body weight gain, significantly higher than control.Also, there was no significantly comparable change in absolute and relative weights of the vital organs, proving its safety and efficacy.
Adults and children suffering from helminth infection became worm-free within 5 days of oral administration of dried BD root powder (Singh and Udupa, 1972).A clinical trial of BD extract as a chemotherapy adjuvant conducted on 50 patients freshly diagnosed as having pulmonary tuberculosis recovered faster than the control.80% of BD-treated patients were relieved from cough in 4 weeks as compared to 52% from among the control.Likewise, 88% of the patients were afebrile in 6 weeks as compared to 60% among the control, with the similar afebrile state setting in by the 8th week in the control.The BD treated group had a higher average weight gain, and a considerably faster sputum conversion rate (Kant et al., 2001).Aqueous plant extract could significantly reduce osmotic fragility of erythrocyte in polycystic end-stage renal disease (ESRD) by altering the composition of erythrocyte membrane or affecting the intracellular sodium and improving the oxidative stress (Sathyapriya et al., 2009).The haematological, biochemical and urine parameters of patients with Type-I or Type-II diabetic nephropathy (DM) with >500 mg proteinuria daily and >5 mg/ dL serum Cr were examined every month for 6 months in a clinical trial after dividing them into two groups (14 patients of 40-70 years with 60.78 ± 6.37 years mean age in group I and 11 of 45-73 years with 60.27 ± 9.00 years mean age in group II).All patients were having edema, anorexia, weakness and vomiting symptoms.While Ramipril (a standard drug) reduced 24-h urine protein excretion significantly, six-month BD treatment decreased it only to a statistically insignificant level (Singh et al., 2010).

Discussion
By categorising the collected relevant literature and conducting bibliometric analyses, it was observed that the maximum number of literature (15) were related to organ protective role of BD, followed by the literature related to metabolic disorders (12), anti-inflammatory property (9), antimicrobial and antiparasitic (8) and anticancer (5) potentials.This provides a strong reason to consider the plant and it extracts as a panacea to treat numerous physiological, pathological and lifestyle related illnesses.
Numerous crude extraction, purification and optimisation techniques for scale-up have been suggested in recent reports.Chromatographic technique is advantageous in evaluating retinoid and phenolic acids due to the ease of sample preparation, chemicals optimisation and the scope to simultaneously compare several samples.Chromatogram comparison allows detect similarities and differences between the various bioactive extracts under investigation even at the minutest level.
Eupalitin-3-O-D-galactopyranoside has powerful hepatoprotective properties against carbon tetrachloride-induced toxicity.It could be crystallised from sedimented residue, making it a simple, quick and the most economical commercially viable scale-up technique.This novel approach was used to isolate Eupalitin-3-O-β-D-galactopyranoside with up to 0.1578% w/w yield.Obtaining Eupalitin-3-O-β-D-galactopyranoside from hydro-alcoholic extract of BD employing high-performance thin layer chromatography (HPTLC) technique through a single solvent system (toluene:acetone:water:5:15:1) was optimised, validated and quantified.
Due to altered lifestyle, less physical exercise, work stress, increasing physical stress, junk food preference and rising childhood obesity, the number of diabetics is in the rise at an alarming rate in recent time worldwide including India.To address such metabolic disorders, nutraceuticals including herbal therapeutants like BD as dietary supplement could be suggested.BD reportedly has excellent antidiabetic activity that regulates and optimises biochemical factors in diabetic test models as listed in Table 1.Such wonder manifestation of BD is attributable to a probable mode of action of the phytoconstituents to ameliorate diabetes as proposed in Figure 3.More focused clinical trials and evidence-based intensive investigations to validate its efficacy are needed.Further, the multifarious other benefits extended by BD makes it a genuinely wonder herb that needs it due place in the society for sustainable human wellbeing.
Although several studies validate the traditional use of BD, but most of them lack in deciphering the mechanism of action of the underlying bioactive therapeutic phytocompounds in preventing or protecting against infectious diseases.Investigations confirming its molecular-level action against various diseases, the pharmacology and the toxicology of unexplored secondary metabolites if any could be undertaken.

Conclusion and future prospects
BD reportedly has multiple and multifunctional pharmacological traits including antifungal, anticancer, antibacterial, antidiabetic, antiparasitic, cardioprotective, hepatoprotective, renoprotective, anti-inflammatory and antifertility characteristics as opined and concluded by numerous investigators.Though the reports on the pharmacological properties of BD are many, the molecular action of the therapeutic phytocompounds in preventing or protecting against infectious diseases, for instance, most of them are inconclusive.Although there are multiple reports on antimicrobial activities yet the molecular mechanisms of specific interaction between the purified compounds and the microbial effector proteins/toxins or their interference with molecular pathogenesis are limited.Thus, clinical trials and advance studies targeting the understanding of the mechanisms of action at the molecular level can be further undertaken to decipher it, especially of the isolated unexplored secondary metabolites in BD.Additionally, investigations to understand prophylactic and therapeutic roles of these phytomolecules at the molecular level using appropriate test models need to be prioritised.

FIGURE 2
FIGURE 2Graphical presentation of the various medicinal virtues of BD.

FIGURE 3 A
FIGURE 3A schematic presentation of the various medicinal benefits of BD on human tissues and organs.

FIGURE 5
FIGURE 5Cardioprotective role of bioactive compounds in BD.

TABLE 1 A
list of bioactive properties of BD-extracts to counter metabolic disorders.
STZ-induced diabetic rat Restored the elevated renal and hepatic markers and carbohydrate metabolising enzyme levels to normal, like glibenclamide in lowering glucose and lipid (serum cholesterol, triglycerides, VLDL-C, LDL-C and phospholipids) levels, augmenting the level of HDL-C in test rats Vasundhara and Devi (2018) 5 (Ethyl acetate, ethanol and water) extracts from the aerial parts of BD (100-250 μg/mL) Sprague Dawley rat Dose-dependent, it inhibited jejunal glucose and enhanced muscle glucose uptake; exhibited strong antioxidant potentials and high anti-lipidemic and anti-hyperglycemic activities by inhibiting fat and carbohydrate digestion besides abdominal glucose intake and increasing muscle glucose uptake Oyebode et al. (2018) 6 Methanol extract of leaves STZ-induced diabetic rat Reduced glucose and HbA1c and elevated serum insulin and insulin receptor A after 28-day treatment at par with glibenclamide.Both standard drug and the extract modulated carbohydrate-metabolising enzyme and liver glycogen activities significantly by up-regulating mRNA expression of Glucose Transporter-2 (Glut2) Ibrahima et al. (2018) 7 Methanolic root extract, purified bioactive fraction STZ-induced diabetic rat Significant reduction in fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) after 14-week treatment; superior plasma lipid profile, free fatty acid levels, phospholipids, HMG-CoA reductase activity, conjugated diene levels, lipid hydroperoxide levels and malondialdehyde (MDA); antioxidant enzyme (SOD, CAT, GPx, GR, and GST) activity was restored Akhter et al. (2019) 8 Methanolic root extracts of W. somnifera, BD and combination (200 mg/kg/day) Dexamethasone-induced diabetic rat Both extracts reduced blood glucose level, serum TG, TC, VLDL levels, and increased HDL levels; while there was no change individually, combined it increased body weight and significantly decreased the LDL levels in diabetic rats TG, TC, FFA, LDL, VLDL increased and HDL level in serum and heart significantly decreased; biochemical parameters in the treated groups were comparable to control Shameela et al. (2015) (Continued on following page)

TABLE 1 (
Continued) A list of bioactive properties of BD-extracts to counter metabolic disorders.

TABLE 3 A
list of reported anti-inflammatory and curing properties of BD.

TABLE 4 A
list of reported anticancer and antiproliferative properties of BD.

TABLE 5 A
list of the reported protective role of major human organs by BD.

TABLE 5 (
Continued) A list of the reported protective role of major human organs by BD.