Approaches to Decrease Hyperglycemia by Targeting Impaired Hepatic Glucose Homeostasis Using Medicinal Plants

Abstract

Liver plays a pivotal role in maintaining blood glucose levels through complex processes which involve the disposal, storage, and endogenous production of this carbohydrate. Insulin is the hormone responsible for regulating hepatic glucose production and glucose storage as glycogen, thus abnormalities in its function lead to hyperglycemia in obese or diabetic patients because of higher production rates and lower capacity to store glucose. In this context, two different but complementary therapeutic approaches can be highlighted to avoid the hyperglycemia generated by the hepatic insulin resistance: 1) enhancing insulin function by inhibiting the protein tyrosine phosphatase 1B, one of the main enzymes that disrupt the insulin signal, and 2) direct regulation of key enzymes involved in hepatic glucose production and glycogen synthesis/breakdown. It is recognized that medicinal plants are a valuable source of molecules with special properties and a wide range of scaffolds that can improve hepatic glucose metabolism. Some molecules, especially phenolic compounds and terpenoids, exhibit a powerful inhibitory capacity on protein tyrosine phosphatase 1B and decrease the expression or activity of the key enzymes involved in the gluconeogenic pathway, such as phosphoenolpyruvate carboxykinase or glucose 6-phosphatase. This review shed light on the progress made in the past 7 years in medicinal plants capable of improving hepatic glucose homeostasis through the two proposed approaches. We suggest that Coreopsis tinctoria, Lithocarpus polystachyus, and Panax ginseng can be good candidates for developing herbal medicines or phytomedicines that target inhibition of hepatic glucose output as they can modulate the activity of PTP-1B, the expression of gluconeogenic enzymes, and the glycogen content.

Introduction

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood sugar levels (hyperglycemia), caused by insulin malfunctioning, deficient insulin secretion, or both (Liu et al., 2019). Type 2 diabetes (T2D) is the most important type of DM due to its high worldwide prevalence (American Diabetes Association, 2021). It is characterized by insulin resistance, which is defined as a poor response of insulin-sensitive tissues to normal insulin concentration (Mlinar et al., 2007). The main cause of insulin resistance has been associated to an obesogenic environment in which large amounts of free fatty acids and adipokines are responsible for impairing insulin signaling by increasing serine phosphorylation that inhibits tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrates (IRSs) (DeFronzo et al., 2015). However, it has also been reported that protein tyrosine phosphatases (PTPs) could have a more important role since they are upregulated in insulin resistant states. Insulin action is negative regulated by PTPs, particularly the PTP-1B, because they promote the dephosphorylation of tyrosine residues of IR and IRSs (Saltiel and Kahn, 2001). When insulin signaling is impaired in liver by either insulin resistance or low insulin levels, the glucose storage and production is dysregulated, increasing the hepatic glucose output rates yielding hyperglycemia in diabetic patients.

Liver represents a crucial therapeutic target for treating hyperglycemia in T2D because hepatic glucose output is the pathophysiological abnormality that contributes the most to the hyperglycemic state in fasting and postprandial state as a consequence of hepatic insulin resistance (Sharabi et al., 2015). During the overnight fast (postabsorptive state), the liver of a normal person produces glucose at a rate of approximately 1.8–2 mg/kg. min. However, this rate increases around 0.5 mg/kg min in a patient with T2D, promoting a significant rise in the basal state of glucose production (Cersosimo et al., 2018). After food ingestion and the subsequent increase in insulin levels, the suppression of glucose production is slower in a diabetic patient, promoting an evident postprandial hyperglycemia due to the excess of glucose produced in addition to that from the exogenous source (Rizza, 2010).

Medicinal plants and natural products have shown to have numerous benefits on processes involved in glucose and lipid metabolism, leading to correct homeostasis imbalances that promote metabolic diseases such as T2D (Li J. et al., 2018; Xu L. et al., 2018; Saadeldeen et al., 2020). Unlike the classic “on-target” paradigm in pharmacology, namely a drug with a specific target, the polypharmacology approach, or the binding of a drug to more than one target, could be more effective against a disease as complex as T2D due to its multiple pathophysiological abnormalities (Reddy and Zhang, 2013). In this context, extract plants and phytochemicals isolated from medicinal plants exhibit multiple mechanisms of action on assorted metabolic targets that are involved in glucose homeostasis. Therefore, efforts have been made to describe all the beneficial effects on metabolism of these extracts and molecules in recent years.

The current review summarizes the medicinal plants reported from 2015 that can potentially decrease hyperglycemia resulting from imbalance in hepatic glucose metabolism by two different approaches: improving hepatic insulin resistance by inhibiting PTP-1B and decreasing hepatic glucose output by inhibiting rate-limiting enzymes involved in the storage and production of glucose.

Methodology

Two separate searches were performed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) (Page et al., 2021) in the following databases: Scopus, Clarivate and PubMed (Figure 1). The first involved studies related to extracts or phytochemicals tested against the activity or expression of PTP-1B enzyme, while in the second, studies with extracts or phytochemicals with an effect on the glucose-producing pathways were sought. Only records related to the study of medicinal plants and their isolated compounds were considered.

FIGURE 1

Therapeutic Approaches to Reduce Hyperglycemia Resulting From Impaired Hepatic Glucose Homeostasis

Each insulin-sensitive tissue presents abnormal characteristics that contribute to hyperglycemia in an insulin-resistant state. The underlying mechanisms that give rise to insulin resistance converge on deficient insulin signalling that limits the activation of factors involved in energy metabolism. In obesity and T2D, insulin resistance has been linked mainly to defects in the signalling pathway of phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt), particularly to the Akt2 isoform (Cusi et al., 2000; Krook et al., 2000).

In normal conditions, the insulin secreted by pancreatic β cell binds to its receptor in the target cell, activating the tyrosine kinase activity, which promotes the receptor autophosphorylation and the subsequent phosphorylation of IRSs, mainly IRS-1 and IRS-2, in tyrosine residues. Afterwards, the enzyme P13K is recruited and activated by IRS to convert phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane to phosphatidylinositol 3,4,5-triphosphate (PIP3), which facilitates the phosphorylation and activation of Akt at two important sites: by phosphoinositide-dependent kinase 1 (PDK1) at residue Thr308 of the catalytic domain, and by mammalian target rapamycin complex 2 (mTORC2) at residue Ser473 of the regulatory domain (Schultze et al., 2012). Specifically in liver, the activated Akt enzyme is responsible for phosphorylating different factors that are involved in the regulation of processes such as glycogen synthesis, gluconeogenesis, and glycogenolysis, which are activated or inhibited under different nutritional circumstances (Dimitriadis et al., 2021).

Due to hepatic insulin resistance, this hormone losses its ability to regulate glucose metabolism in liver, resulting in enhanced glucose output that contributes greatly to fasting and postprandial hyperglycemia, namely glycogen synthesis is reduced, and production of glucose is increased (Figure 2). Therefore, we proposed two approaches by which medicinal plants could ameliorated hyperglycemia through enhancing hepatic glucose metabolism: improving the function of insulin in the liver by inhibiting the enzyme PTP-1B and modulating the hepatic production/storage of glucose by regulating the enzymes involved in gluconeogenesis, glycogenolysis, and glycogenesis.

FIGURE 2

Inhibition of Protein Tyrosine Phosphatase 1B

The modification of proteins through phosphorylation and dephosphorylation of tyrosine residues represents one of the main mechanisms of cell signaling regulation (Alonso et al., 2016), which is carried out by two superfamilies of enzymes: protein tyrosine kinases (PTKs), and PTPs. In this regard, the classical PTP subfamily possess a domain of 240–250 amino acids characterized by a conserved site that exhibits a catalytic mechanism based on cysteine (Denu and Dixon, 1998). Specifically, the enzyme PTP-1B is a classic intracellular PTP widely distributed in mammalian tissues that is anchored on the cytoplasmic side of the endoplasmic reticulum membrane. Despite its localization, the PTP-1B enzyme can access its substrates located on the surface of the plasma membrane during endocytosis, biosynthesis, and by the movement of the endoplasmic reticulum towards the plasma membrane in specific regions (Bakke and Haj, 2015).

Since its first isolation from the human placenta in 1988 by Tonks et al., 1988 PTP-1B has become an attractive research object due to its direct link with the etiopathogenesis of insulin resistance. In addition to the processes promoted by the obesogenic inflammatory environment, such as the serine/threonine phosphorylation of IR and IRS, and their proteasomal degradation (Mlinar et al., 2007; Ahmed et al., 2021), the dephosphorylation of these components by PTP-1B has also been implied to the termination of the insulin signal (Ahmad et al., 1995; Kenner et al., 1996; Chen et al., 1997).

Experimental data obtained from various studies have shown that the PTP-1B enzyme is one of the main negative regulators of the insulin signaling pathway. For instance, studies performed in PTP-1B knock-out mice have been shown that the absence of this enzyme produces healthy organisms that exhibit enhanced insulin sensitivity, protection against the weight gain generated by high-fat diet, and increased hepatic phosphorylation of IR and IRS after an intraperitoneal insulin injection (Elchebly et al., 1999; Klaman et al., 2000). On the other hand, it has been reported an increased PTP-1B activity in hepatic cytosolic fractions isolated from streptozotocin (STZ)-hyperglycemic rats (Meyerovitch et al., 1989), while augmented hepatic microsomal enzyme activity, content of protein, and mRNA levels have only been observed after 2 weeks of insulin treatment in these insulinopenic organisms, suggesting that elevated insulin levels are necessary to modify PTP-1B content and activity, namely hyperinsulinemia caused by insulin resistance may lead to altered PTP-1B expression and activity (Ahmad and Goldstein, 1995). Additionally, it has also been shown that insulin rises hepatic microsomal PTP-1B activity in rat hepatoma cells (Hashimoto and Goldstein, 1992). Likewise, abnormal expression and activity of PTP-1B have been reported in skeletal muscle of insulin-resistant obese people (Ahmad et al., 1997), as well as in non-obese Goto-Kakizaki rats with spontaneously generated insulin resistance (Dadke et al., 2000), and in STZ-hyperglycemic rats fed with high-fat diet (Wu et al., 2005).

Based on the aforementioned, the PTP-1B inhibition represents a good therapeutic target for the treatment of insulin resistance-related diseases, such as DM2 (Zhang et al., 2006). Hence, an arsenal of molecules with inhibitory capacity of PTP-1B activity has been generated in recent years. The methodological approaches that have been applied are the rational design of synthetic phospho-(tyrosine)-mimetic molecules to be used as competitive inhibitors, considering the structural characteristics of the protein, and the search for molecules from natural sources (Sun et al., 2018). The latter is based on the statement that nature has a great variety of structures that present diverse pharmacological effects (Atanasov et al., 2021), so natural products can be used as a starting point for the creation of powerful inhibitors.

Table 1 summarizes all medicinal plants and their identified compounds that have proved to inhibit the activity or expression of PTP-1B since 2015. It was obtained a total of 125 medicinal plants used in various traditional medicine systems around the world, mainly represented in eastern folk, such as Chinese and Vietnamese. Morus alba L. (Moraceae), a plant used in the traditional Chinese system, has been the most evaluated for this purpose. In addition to direct PTP-1B activity inhibition and molecular docking studies, some extracts and compounds were assessed to improve glucose and lipid metabolism in vivo, such as lowering blood glucose levels, improved insulin resistance and glucose intolerance, and improved lipid profile. Furthermore, their effect on glucose uptake and phosphorylation of some components of insulin signaling, such as IR, IRS, and Akt, was evaluated in cell cultures under insulin-resistant conditions.

Inhibition of Hepatic Glucose Output by Modulating Glucose Metabolism in Liver

The liver is a key organ that plays a crucial role in the regulation of blood glucose because it manages both storage and synthesis of glucose. The latter involves two metabolic pathways: glycogenolysis and gluconeogenesis, which constitute total hepatic glucose production (HGP) (Lee et al., 2015). Glycogenolysis consists of glycogen breakdown into glucose, being half of the basal HGP in fasting and decreasing the glycogen concentration at an almost linear rate during the first 22 h (Rothman et al., 1991; Cersosimo et al., 2018). In fasting, it is controlled by glucagon and epinephrine that activate glycogen phosphorylase (GP), the major enzyme responsible for digesting glycogen by releasing glucose 1-phosphate. In feeding condition, insulin inhibits glycogen breakdown and promotes glycogen synthesis through the activation of Akt and protein phosphatase 1 (PP1), leading the deactivation of both GP and glycogen synthase kinase-3 (GSK3), which in its active form (dephosphorylated), inactivates glycogen synthase (GS) (Han et al., 2016).

Gluconeogenesis, on the other hand, is defined as the production of glucose from a molecule that is not a carbohydrate. Its main substrates are pyruvate, glycerol, and amino acids such as alanine (Hanson and Owen, 2013). Another way to denote gluconeogenesis is as “reverse glycolysis” since both share not only substrates and final products, but also many enzymes. However, the direction of the reactions catalyzed in gluconeogenesis goes in the opposite direction, so the steps that are not shared with glycolysis can be determined as regulatory steps. These reactions are catalyzed by four rate-limiting enzymes: pyruvate carboxylase (PC), which is responsible for converting pyruvate into oxaloacetate; phosphoenolpyruvate carboxykinase (PEPCK), that converts oxaloacetate to phosphoenolpyruvate; fructose 1,6-bisphosphatase (FBPase), that dephosphorylates fructose 1,6-bisphosphate obtaining fructose 6-phosphate; and glucose 6-phosphatase (G6Pase), which is responsible for removing the phosphate group from glucose 6-phosphate, yielding novo synthesized glucose (Postic et al., 2004).

In the diabetic state, increased rates of HGP are observed as a result of an imbalance of various factors, such as the augmented availability of gluconeogenic substrates, the resistance of the liver to the action of insulin, and elevated levels of glucagon that activate HGP (Sharabi et al., 2015). Due to all these factors, the inhibition of HGP turns out to be an important therapeutic target for the reduction of hyperglycemia observed in T2D patients. In this regard, Table 2 summarizes the works made between 2015 and 2021 with extracts or natural products from 47 medicinal plants that showed to modulate hepatic glucose metabolism by inhibiting glucose production or promoting glycogen synthesis. As it can be observed, decreasing the expression of PEPCK and G6Pase is the principal mechanism related to gluconeogenesis inhibition, while phosphorylation of GSK3, promotion of GS activity, and inhibition of GP are the main mechanisms involved in glycogen breakdown and synthesis. Furthermore, although PI3K/Akt pathway stands out as a good pharmacological target to reduce insulin resistance, medicinal plants and their phytochemicals can also decrease HGP through AMP-activated protein kinase (AMPK).

Discussion

Insulin resistance in liver leads to the release of large amounts of glucose into the bloodstream that affects long-term homeostasis. The regulation of hepatic glucose output represents a good pharmacological target for the control of metabolic diseases such as T2D, which are characterized by the presence of this pathophysiological phenomenon. The search for new molecules capable of regulating hepatic glucose metabolism from medicinal plants has focused on screening for phytochemicals that can directly inhibit key enzymes in glucose-producing pathways. However, considering compounds with the ability to also decrease the activity of the enzymes involved in terminating the insulin signal could result in more effective glycemic control.

According to the bibliographic search, plants used in different systems of traditional medicine have shown the ability to inhibit the activity or expression of PTP-1B, which could indicate that they have a potential inhibitory effect on HGP. The determination of biological activity of full extracts and compounds isolated from medicinal plants has been approached through different perspectives. Generally, the medicinal plant is first identified using an ethnopharmacological approach. Afterwards, different types of extracts are elaborated (aqueous, ethanolic, methanolic, etc.) and then tested on the biological activity to be evaluated following several paths: 1) direct inhibition enzymatic assays, which can be complemented with structure-activity relationship (SAR) studies and molecular docking analysis to find the possible structures responsible for the bioactivity, relating them with the binding of amino acid residues present at the catalytic or regulatory sites (regarding isolated compounds); 2) the use of cell cultures to evaluate the effect of the extract or compound on the expression and protein levels of key enzymes; and 3) in vivo studies, where diabetic (hyperglycemic) animals induced with STZ or alloxan, or insulin-resistant animals generated by the consumption of high-fat diet are used.

Regarding PTP-1B, most of the studies published between 2015 and 2021 focused on conducting enzyme activity assays, and few of them had a multidisciplinary approach that encompassed enzyme assays and in vitro or in vivo studies. The main problem with the first type of studies is that, although the inhibition potency and selectivity of the molecule over the enzyme are directly evaluated, the pharmacokinetic properties of the compound are omitted. This particularity stands out since it has been reported that, despite having excellent inhibitory activity, many compounds lack adequate cellular permeability, namely they present poor absorption and low bioavailability (Zhang et al., 2017). Another aspect to highlight is that PTP-1B is almost identical to TC-PTP, another member of the PTP family with 74% identity at the catalytic site, so it is important that the identified inhibitors have a high selectivity towards PTP-1B to avoid unwanted effects (Dewang et al., 2005). Considering these facts, it would be necessary in the future to carry out more studies involving as many approaches as possible to obtain a more integrative panorama and to be able to evaluate potential inhibitors considering their pharmacokinetic properties and selectivity. Also, it is encouraged to directly evaluate the effect of medicinal plants and their compounds with reported PTP-1B inhibitory capacity on hepatic glucose metabolism.

In addition to exhibiting PTP-1B inhibitory capacity, some of the medicinal plants reported in Table 1 also improved hepatic glucose metabolism by promoting glucose consumption and glycogen synthesis, upregulating activity or expression of GS, decreasing activity or expression of key enzymes involved in glycogenolysis and gluconeogenesis such as GSK3, GP, PEPCK, FBPase, and G6Pase, and by modulating insulin signaling. The compounds isolated from these plants could have a greater modulatory capacity of hepatic glucose metabolism because they are capable of directly reducing both insulin resistance and glucose production. These species were Astragalus mongholicus (astragaloside IV), Chaenomeles japonica, Duranta erecta, Eriobotrya japonica (maslinic acid, corosolic acid, oleanolic acid, and ursolic acid), Symplocos cochinchinensis, Thonningia sanguinea (2′-O- (3-O-galloyl-4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)-3-hydroxyphloretin, 4′-O-(4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)- phloretin, 2′-O-(3-O-galloyl-4,6-O-Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin, thonningianin A, and thonningianin B), Vaccinium uliginosum (cyanidin-3-arabinoside, delphinidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-glucoside, malvidin-3-galactoside, petunidin-3-glucoside, procyanidin B1, and procyanidin B2), and Vigna radiata. On the other hand, since Coreopsis tinctoria, Lithocarpus polystachyus, and Panax ginseng were documented in both Tables 1, 2, their isolated compounds may have better glycemic control.

This work focused on summarizing the medicinal plants with the potential capacity to reduce hyperglycemia resulting from an imbalance in the hepatic metabolism of glucose, encompassing two different approaches: the inhibition of PTP-1B (improvement of hepatic insulin resistance), and the modulation of enzymes involved in gluconeogenesis and glycogenolysis/glycogenesis (decreased hepatic glucose output). In recent years, PTP-1B research has focused on the characterization of different phytochemicals from medicinal plants, such as phenolic compounds, terpenes, and alkaloids. The main methodology used was to carry out direct enzyme inhibition tests to evaluate the potency of these molecules, omitting important aspects such as selectivity or pharmacokinetics. Therefore, it is proposed to use of multidisciplinary approaches that involve in vitro studies, such as the use of cell lines or primary culture to evaluate the effect of the extracts and compounds on expression and protein levels, and in vivo studies, where the concentration of the compound in systemic circulation and its duration is determined, as well as the transformation processes involved. In this regard, not only the inhibitory activity of the compounds is evaluated, but also the impact on other pharmacological aspects that can only be observed using animal models.

On the other hand, research on medicinal plants that modulate hepatic glucose metabolism has primary focused on testing full extracts rather than compounds. However, it is worth mentioning that mixtures could have synergistic effects capable of regulating multiple targets (Caesar and Cech, 2019) and therefore compound fractions may exhibit more bioactivity than isolated molecules. Further studies are needed to identify potential multi-target phytochemicals in plants listed in Table 2. Finally, it is expected that this review will provide greater knowledge of medicinal plants and compounds for the development of drugs that improving hepatic glucose metabolism as a therapeutic target for the treatment of T2D.

We suggest that Coreopsis tinctoria, Lithocarpus polystachyus, and Panax ginseng can be good candidates for developing herbal medicines or phytomedicines that target inhibition of hepatic glucose output as they can modulate the activity of PTP-1B, the expression of gluconeogenic enzymes, and the glycogen content. However, only their full extracts are tested until now. Therefore, compounds responsible for the effects mentioned above have not been identified, and pharmacological and toxicological tests in animal models are required to assess their efficacy and safety, with the aim of moving forward to carry out clinical studies.

References

• 1

  Abdel-RahmanR. F.EzzatS. M.OgalyH. A.Abd-ElsalamR. M.HessinA. F.FekryM. I.et al (2020). Ficus Deltoidea Extract Down-Regulates Protein Tyrosine Phosphatase 1B Expression in a Rat Model of Type 2 Diabetes Mellitus: a New Insight into its Antidiabetic Mechanism. J. Nutr. Sci.9, e2. 10.1017/jns.2019.40

  • CrossRef
  • Google Scholar

• 2

  Abdel-SattarE.El-MaraghyS. A.El-DineR. S.RizkS. M. (2016). Russelioside B, a Pregnane Glycoside Ameliorates Hyperglycemia in Streptozotocin Induced Diabetic Rats by Regulating Key Enzymes of Glucose Metabolism. Chem. Biol. Interact.252, 47–53. 10.1016/j.cbi.2016.03.033

  • CrossRef
  • Google Scholar

• 3

  AbdjulD. B.YamazakiH.MaarisitW.RotinsuluH.WewengkangD. S.SumilatD. A.et al (2017). Oleanane Triterpenes with Protein Tyrosine Phosphatase 1B Inhibitory Activity from Aerial Parts of Lantana Camara Collected in Indonesia and Japan. Phytochemistry144, 106–112. 10.1016/j.phytochem.2017.08.020

  • CrossRef
  • Google Scholar

• 4

  AbdjulD. B.YamazakiH.MaarisitW.KirikoshiR.TakahashiO.LosungF.et al (2018). Protein Tyrosine Phosphatase 1B Inhibitory Components and a New Unique N -alkylamide Derivative with an Endoperoxide Bridge from Aerial Parts of Indonesian Spilanthes Paniculata. Phytochemistry Lett.24, 71–74. 10.1016/j.phytol.2018.01.013

  • CrossRef
  • Google Scholar

• 5

  AhmadF.AzevedoJ. L.CortrightR.DohmG. L.GoldsteinB. J. (1997). Alterations in Skeletal Muscle Protein-Tyrosine Phosphatase Activity and Expression in Insulin-Resistant Human Obesity and Diabetes. J. Clin. Invest.100, 449–458. 10.1172/JCI119552

  • CrossRef
  • Google Scholar

• 6

  AhmadF.GoldsteinB. J. (1995). Alterations in Specific Protein-Tyrosine Phosphatases Accompany Insulin Resistance of Streptozotocin Diabetes. Am. J. Physiol.268, E932–E940. 10.1152/ajpendo.1995.268.5.e932

  • CrossRef
  • Google Scholar

• 7

  AhmadF.LiP. M.MeyerovitchJ.GoldsteinB. J. (1995). Osmotic Loading of Neutralizing Antibodies Demonstrates a Role for Protein-Tyrosine Phosphatase 1B in Negative Regulation of the Insulin Action Pathway. J. Biol. Chem.270, 20503–20508. 10.1074/jbc.270.35.20503

  • CrossRef
  • Google Scholar

• 8

  AhmedB.SultanaR.GreeneM. W. (2021). Adipose Tissue and Insulin Resistance in Obese. Biomed. Pharmacother.137, 111315. 10.1016/j.biopha.2021.111315

  • CrossRef
  • Google Scholar

• 9

  AlonsoA.Nunes-XavierC. E.BayónY.PulidoR. (2016). “The Extended Family of Protein Tyrosine Phosphatases,” in Methods in Molecular Biology. Editor PulidoR. (New York: Humana Press), 1–23. 10.1007/978-1-4939-3746-2_1Protein Tyrosine Phosphatases

  • CrossRef
  • Google Scholar

• 10

  American Diabetes Association (2021). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care44, S15–S33. 10.2337/dc21-S002

  • CrossRef
  • Google Scholar

• 11

  AnJ. P.HaT. K.KimJ.ChoT. O.OhW. K. (2016). Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia Quinata. Molecules21. 10.3390/molecules21081091

  • CrossRef
  • Google Scholar

• 12

  Andrade-CettoA.Espinoza-HernándezF.Mata-TorresG.Escandón-RiveraS. (2021b). Hypoglycemic Effect of Two Mexican Medicinal Plants. Plants (Basel)10, 2060. 10.3390/plants10102060

  • CrossRef
  • Google Scholar

• 13

  Andrade-CettoA.Espinoza-HernándezF.Mata-TorresG. (2021a). Hypoglycemic Effect of Calea Urticifolia (Mill.) DC. Evidence-Based Complement. Altern. Med.2021, 1–10. 10.1155/2021/6625009

  • CrossRef
  • Google Scholar

• 14

  AntuK. A.RiyaM. P.NairA.MishraA.SrivastavaA. K.RaghuK. G. (2016). Symplocos Cochinchinensis Enhances Insulin Sensitivity via the Down Regulation of Lipogenesis and Insulin Resistance in High Energy Diet Rat Model. J. Ethnopharmacol.193, 500–509. 10.1016/j.jep.2016.09.050

  • CrossRef
  • Google Scholar

• 15

  Arancibia-RadichJ.González-BlázquezR.AlcaláM.Martín-RamosM.VianaM.ArribasS.et al (2019). Beneficial Effects of Murtilla Extract and Madecassic Acid on Insulin Sensitivity and Endothelial Function in a Model of Diet-Induced Obesity. Sci. Rep.9, 599. 10.1038/s41598-018-36555-1

  • CrossRef
  • Google Scholar

• 16

  AtanasovA. G.ZotchevS.ZotchevS. B.DirschV. M.SupuranC. T. (2021). The International Natural Product Sciences Taskforce, and Supuran, CNatural Products in Drug Discovery: Advances and Opportunities. Nat. Rev. Drug Discov.20, 200–216. 10.1038/s41573-020-00114-z

  • CrossRef
  • Google Scholar

• 17

  BakkeJ.HajF. G. (2015). Protein-tyrosine Phosphatase 1B Substrates and Metabolic Regulation. Semin. Cel Dev Biol37, 58–65. 10.1016/j.semcdb.2014.09.020

  • CrossRef
  • Google Scholar

• 18

  BaoS.WuY. L.WangX.HanS.ChoS.AoW.et al (2020). Agriophyllum Oligosaccharides Ameliorate Hepatic Injury in Type 2 Diabetic Db/db Mice Targeting INS-R/IRS-2/PI3K/AKT/PPAR-γ/Glut4 Signal Pathway. J. Ethnopharmacol.257, 112863. 10.1016/j.jep.2020.112863

  • CrossRef
  • Google Scholar

• 19

  BegmatovN.LiJ.BobakulovK.NumonovS.AisaH. A. (2020). The Chemical Components of Coreopsis Tinctoria Nutt. And Their Antioxidant, Antidiabetic and Antibacterial Activities. Nat. Prod. Res.34, 1772–1776. 10.1080/14786419.2018.1525377

  • CrossRef
  • Google Scholar

• 20

  CaesarL. K.CechN. B. (2019). Synergy and Antagonism in Natural Product Extracts: When 1 + 1 Does Not Equal 2. Nat. Prod. Rep.36, 869–888. 10.1039/c9np00011a

  • CrossRef
  • Google Scholar

• 21

  CaiJ.ZhaoL.TaoW. (2015). Potent Protein Tyrosine Phosphatase 1B (PTP1B) Inhibiting Constituents from Anoectochilus Chapaensis and Molecular Docking Studies. Pharm. Biol.53, 1030–1034. 10.3109/13880209.2014.957781

  • CrossRef
  • Google Scholar

• 22

  CaoX.YangX.WangP.LiangY.LiuF.TuerhongM.et al (2017). Polycyclic Phloroglucinols as PTP1B Inhibitors from Hypericum Longistylum: Structures, PTP1B Inhibitory Activities, and Interactions with PTP1B. Bioorg. Chem.75, 139–148. 10.1016/j.bioorg.2017.09.001

  • CrossRef
  • Google Scholar

• 23

  CersosimoE.TriplittC.Solis-HerreraC.MandarinoL. J.DeFronzoR. A. (2018). “Pathogenesis of Type 2 Diabetes Mellitus,” in ” in Endotext. Editor FeingoldK. R. (South Dartmouth: MDText.com, Inc.). . http://www.ncbi.nlm.nih.gov/pubmed/25905339 (Accessed September 1, 2021).

  • Google Scholar

• 24

  ChenH.WertheimerS. J.LinC. H.KatzS. L.AmreinK. E.BurnP.et al (1997). Protein-tyrosine Phosphatases PTP1B and Syp Are Modulators of Insulin-Stimulated Translocation of GLUT4 in Transfected Rat Adipose Cells. J. Biol. Chem.272, 8026–8031. 10.1074/jbc.272.12.8026

  • CrossRef
  • Google Scholar

• 25

  ChoiJ. S.AliM. Y.JungH. A.OhS. H.ChoiR. J.KimE. J. (2015). Protein Tyrosine Phosphatase 1B Inhibitory Activity of Alkaloids from Rhizoma Coptidis and Their Molecular Docking Studies. J. Ethnopharmacol.171, 28–36. 10.1016/j.jep.2015.05.020

  • CrossRef
  • Google Scholar

• 26

  CusiK.MaezonoK.OsmanA.PendergrassM.PattiM. E.PratipanawatrT.et al (2000). Insulin Resistance Differentially Affects the PI 3-kinase- and MAP Kinase-Mediated Signaling in Human Muscle. J. Clin. Invest.105, 311–320. 10.1172/JCI7535

  • CrossRef
  • Google Scholar

• 27

  DadkeS. S.LiH. C.KusariA. B.BegumN.KusariJ. (2000). Elevated Expression and Activity of Protein-Tyrosine Phosphatase 1B in Skeletal Muscle of Insulin-Resistant Type II Diabetic Goto-Kakizaki Rats. Biochem. Biophys. Res. Commun.274, 583–589. 10.1006/bbrc.2000.3188

  • CrossRef
  • Google Scholar

• 28

  de OliveiraK. A.Moreira GomesM. D.VasconcelosR. P.de AbreuE. S.FortunatoR. S.Carneiro LoureiroA. C.et al (2019). Phytomodulatory Proteins Promote Inhibition of Hepatic Glucose Production and Favor Glycemic Control via the AMPK Pathway. Biomed. Pharmacother.109, 2342–2347. 10.1016/j.biopha.2018.11.139

  • CrossRef
  • Google Scholar

• 29

  DeFronzoR. A.FerranniniE.GroopL.HenryR. R.HermanW. H.HolstJ. J.et al (2015). Type 2 Diabetes Mellitus. Nat. Rev. Dis. Primers1, 15019–15022. 10.1038/nrdp.2015.19

  • CrossRef
  • Google Scholar

• 30

  DenuJ. M.DixonJ. E. (1998). Protein Tyrosine Phosphatases: Mechanisms of Catalysis and Regulation. Curr. Opin. Chem. Biol.2, 633–641. 10.1016/S1367-5931(98)80095-1

  • CrossRef
  • Google Scholar

• 31

  DewangP. M.HsuN. M.PengS. Z.LiW. R. (2005). Protein Tyrosine Phosphatases and Their Inhibitors. Curr. Med. Chem.12, 1–22. 10.2174/97816080520731090401037110.2174/0929867053363504

  • CrossRef
  • Google Scholar

• 32

  DimitriadisG. D.MaratouE.KountouriA.BoardM.LambadiariV. (2021). Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-dependent and Insulin-independent Mechanisms: An Integrative Approach. Nutrients13, 1–33. 10.3390/nu13010159

  • CrossRef
  • Google Scholar

• 33

  DivyaN.RengarajanR. L.RadhakrishnanR.Fathi Abd AllahE.AlqarawiA. A.HashemA.et al (2019). Phytotherapeutic Efficacy of the Medicinal Plant Terminalia catappa L. Saudi J. Biol. Sci.26, 985–988. 10.1016/j.sjbs.2018.12.010

  • CrossRef
  • Google Scholar

• 34

  EdirsS.JiangL.XinX.AisaH. A. (2018). Anti-diabetic Effect and Mechanism of Kursi Wufarikun Ziyabit in L6 Rat Skeletal Muscle Cells. J. Pharmacol. Sci.137, 212–219. 10.1016/j.jphs.2018.06.011

  • CrossRef
  • Google Scholar

• 35

  EkakitieL. I.OyinloyeB. E.AjiboyeB. O. (2021). The Ameliorative Activity of Chrysobalanus Orbicularis in Streptozotocin-Induced Type II Diabetes Mellitus Rat Model. Heliyon7, e06596. 10.1016/j.heliyon.2021.e06596

  • CrossRef
  • Google Scholar

• 36

  ElcheblyM.PayetteP.MichaliszynE.CromlishW.CollinsS.LoyA. L.et al (1999). Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine phosphatase-1B Gene. Science283, 1544–1548. 10.1126/science.283.5407.1544

  • CrossRef
  • Google Scholar

• 37

  ErukainureO. L.IjomoneO. M.ChukwumaC. I.XiaoX.SalauV. F.IslamM. S. (2020). Dacryodes Edulis (G. Don) H.J. Lam Modulates Glucose Metabolism, Cholinergic Activities and Nrf2 Expression, while Suppressing Oxidative Stress and Dyslipidemia in Diabetic Rats. J. Ethnopharmacol.255, 112744. 10.1016/j.jep.2020.112744

  • CrossRef
  • Google Scholar

• 38

  ErukainureO. L.MopuriR.OyebodeO. A.KoorbanallyN. A.IslamM. S. (2017). Dacryodes Edulis Enhances Antioxidant Activities, Suppresses DNA Fragmentation in Oxidative Pancreatic and Hepatic Injuries; and Inhibits Carbohydrate Digestive Enzymes Linked to Type 2 Diabetes. Biomed. Pharmacother.96, 37–47. 10.1016/j.biopha.2017.09.106

  • CrossRef
  • Google Scholar

• 39

  ErukainureO. L.OyebodeO. A.IjomoneO. M.ChukwumaC. I.KoorbanallyN. A.IslamM. S. (2019a). Raffia palm (Raphia Hookeri G. Mann & H. Wendl) Wine Modulates Glucose Homeostasis by Enhancing Insulin Secretion and Inhibiting Redox Imbalance in a Rat Model of Diabetes Induced by High Fructose Diet and Streptozotocin. J. Ethnopharmacol.237, 159–170. 10.1016/j.jep.2019.03.039

  • CrossRef
  • Google Scholar

• 40

  ErukainureO. L.SanniO.IjomoneO. M.IbejiC. U.ChukwumaC. I.IslamM. S. (2019b). The Antidiabetic Properties of the Hot Water Extract of Kola Nut (Cola Nitida (Vent.) Schott & Endl.) in Type 2 Diabetic Rats. J. Ethnopharmacol.242, 112033. 10.1016/j.jep.2019.112033

  • CrossRef
  • Google Scholar

• 41

  Espinoza-HernándezF.Andrade-CettoA.Escandón-RiveraS.Mata-TorresG.MataR. (2021). Contribution of Fasting and Postprandial Glucose-Lowering Mechanisms to the Acute Hypoglycemic Effect of Traditionally Used Eryngium Cymosum F.Delaroche. J. Ethnopharmacology279, 114339. 10.1016/j.jep.2021.114339

  • CrossRef
  • Google Scholar

• 42

  GovindarajanS.BabuS. N.VijayalakshmiM. A.ManoharP.NoorA. (2021). Aloe Vera Carbohydrates Regulate Glucose Metabolism through Improved Glycogen Synthesis and Downregulation of Hepatic Gluconeogenesis in Diabetic Rats. J. Ethnopharmacol.281, 114556. 10.1016/j.jep.2021.114556

  • CrossRef
  • Google Scholar

• 43

  GujjalaS.PutakalaM.NukalaS.BangeppagariM.RajendranR.DesireddyS. (2017). Modulatory Effects of Caralluma Fimbriata Extract against High-Fat Diet Induced Abnormalities in Carbohydrate Metabolism in Wistar Rats. Biomed. Pharmacother.92, 1062–1072. 10.1016/j.biopha.2017.06.016

  • CrossRef
  • Google Scholar

• 44

  GuoY.DaiR.DengY.SunL.MengS.XinN. (2019). Hypoglycemic Activity of the Extracts of Belamcanda Chinensis Leaves (BCLE) on KK-Ay Mice. Biomed. Pharmacother.110, 449–455. 10.1016/j.biopha.2018.11.094

  • CrossRef
  • Google Scholar

• 45

  GuoZ.NiuX.XiaoT.LuJ.LiW.ZhaoY. (2015). Chemical Profile and Inhibition of α-glycosidase and Protein Tyrosine Phosphatase 1B (PTP1B) Activities by Flavonoids from Licorice (Glycyrrhiza Uralensis Fisch). J. Funct. Foods14, 324–336. 10.1016/j.jff.2014.12.003

  • CrossRef
  • Google Scholar

• 46

  HaM. T.ShresthaS.TranT. H.KimJ. A.WooM. H.ChoiJ. S.et al (2020). Inhibition of PTP1B by Farnesylated 2-arylbenzofurans Isolated from Morus alba Root Bark: Unraveling the Mechanism of Inhibition Based on In Vitro and In Silico Studies. Arch. Pharm. Res.43, 961–975. 10.1007/s12272-020-01269-4

  • CrossRef
  • Google Scholar

• 47

  HanH. S.KangG.KimJ. S.ChoiB. H.KooS. H. (2016). Regulation of Glucose Metabolism from a Liver-Centric Perspective. Exp. Mol. Med.48, e218–10. 10.1038/emm.2015.122

  • CrossRef
  • Google Scholar

• 48

  HanS.-w.ShiS.-m.ZouY.-x.WangZ.-c.WangY.-q.ShiL.et al (2020). Chemical Constituents from Acid Hydrolyzates of Panax Quinquefolius Total Saponins and Their Inhibition Activity to α-glycosidase and Protein Tyrosine Phosphatase 1B. Chin. Herbal Medicines12, 195–199. 10.1016/j.chmed.2020.03.003

  • CrossRef
  • Google Scholar

• 49

  HansonR. W.OwenO. E. (2013). “Gluconeogenesis,” in Metabolism Vitamins And Hormones. Elsevier, 381–386. 10.1016/B978-0-12-378630-2.00040-2

  • CrossRef
  • Google Scholar

• 50

  HaoJ.HanL.ZhangY.WangT. (2020). Docking Studies on Potential Mechanisms for Decreasing Insulin Resistance by the Tangzhiqing Herbal Formula. Evidence-Based Complement. Altern. Med.2020, 1–11. 10.1155/2020/1057648

  • CrossRef
  • Google Scholar

• 51

  HashimotoN.GoldsteinB. J. (1992). Differential Regulation of mRNAs Encoding Three Protein-Tyrosine Phosphatases by Insulin and Activation of Protein Kinase C. Biochem. Biophys. Res. Commun.188, 1305–1311. 10.1016/0006-291X(92)91373-X

  • CrossRef
  • Google Scholar

• 52

  HeX. F.ChenJ. J.LiT. Z.ZhangX. K.GuoY. Q.ZhangX. M.et al (2020). Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum Tsao-Ko. J. Agric. Food Chem.68, 11434–11448. 10.1021/acs.jafc.0c04615

  • CrossRef
  • Google Scholar

• 53

  HouJ. Q.FanC. L.PeiX.ZhangP. L.DengF.JiangW. Q.et al (2019). Psiguadiols A-J, Rearranged Meroterpenoids as Potent PTP1B Inhibitors from Psidium Guajava. J. Nat. Prod.82, 3267–3278. 10.1021/acs.jnatprod.9b00333

  • CrossRef
  • Google Scholar

• 54

  HuY.LiJ.ChangA. K.LiY.TaoX.LiuW.et al (2021). Screening and Tissue Distribution of Protein Tyrosine Phosphatase 1B Inhibitors in Mice Following Oral Administration of Garcinia Mangostana L. Ethanolic Extract. Food Chem.357, 129759–129768. 10.1016/j.foodchem.2021.129759

  • CrossRef
  • Google Scholar

• 55

  HuangG. H.LeiC.ZhuK. X.LiJ. Y.LiJ.HouA. J. (2019). Enantiomeric Pairs of Meroterpenoids from Rhododendron Fastigiatum. Chin. J. Nat. Med.17, 963–969. 10.1016/S1875-5364(19)30119-0

  • CrossRef
  • Google Scholar

• 56

  IghodaroO. M.AkinloyeO. A.UgbajaR. N.OmotainseS. O. (2017). Sapium Ellipticum (Hochst) Pax Ethanol Leaf Extract Modulates Glucokinase and Glucose-6-Phosphatase Activities in Streptozotocin Induced Diabetic Rats. Asian Pac. J. Trop. Biomed.7, 544–548. 10.1016/j.apjtb.2017.05.009

  • CrossRef
  • Google Scholar

• 57

  JhuangH. J.HsuW. H.LinK. T.HsuS. L.WangF. S.ChouC. K.et al (2015). Gluconeogenesis, Lipogenesis, and HBV Replication Are Commonly Regulated by PGC-1α-dependent Pathway. Oncotarget6, 7788–7803. 10.18632/oncotarget.3050

  • CrossRef
  • Google Scholar

• 58

  JiS.LiZ.SongW.WangY.LiangW.LiK.et al (2016). Bioactive Constituents of Glycyrrhiza Uralensis (Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine. J. Nat. Prod.79, 281–292. 10.1021/acs.jnatprod.5b00877

  • CrossRef
  • Google Scholar

• 59

  JiangB.-p.LvQ.-y.XiangJ.-m.LeL.HuK.-p.XuL.-j.et al (2018a). Inhibition of Metabolic Disorders In Vivo and In Vitro by Main Constituent of Coreopsis Tinctoria. Chin. Herbal Medicines10, 157–168. 10.1016/j.chmed.2018.03.004

  • CrossRef
  • Google Scholar

• 60

  JiangL.NumonovS.BobakulovK.QureshiM. N.ZhaoH.AisaH. A. (2015). Phytochemical Profiling and Evaluation of Pharmacological Activities of Hypericum Scabrum L. Molecules20, 11257–11271. 10.3390/molecules200611257

  • CrossRef
  • Google Scholar

• 61

  JiangW.SiL.LiP.BaiB.QuJ.HouB.et al (2018b). Serum Metabonomics Study on Antidiabetic Effects of Fenugreek Flavonoids in Streptozotocin-Induced Rats. J. Chromatogr. B Analyt Technol. Biomed. Life Sci.1092, 466–472. 10.1016/j.jchromb.2018.06.041

  • CrossRef
  • Google Scholar

• 62

  JinD.-X.HeJ.-F.LuoX.-G.ZhangT.-C. (2019). Hypoglycemic Effect of Hypericum Attenuatum Choisy Extracts on Type 2 Diabetes by Regulating Glucolipid Metabolism and Modulating Gut Microbiota. J. Funct. Foods52, 479–491. 10.1016/j.jff.2018.11.031

  • CrossRef
  • Google Scholar

• 63

  JungH. A.AliM. Y.ChoiJ. S. (2016). Promising Inhibitory Effects of Anthraquinones, Naphthopyrone, and Naphthalene Glycosides, from Cassia Obtusifolia on α-Glucosidase and Human Protein Tyrosine Phosphatases 1B. Molecules22, 28. 10.3390/molecules22010028

  • CrossRef
  • Google Scholar

• 64

  JungH. J.SeongS. H.AliM. Y.MinB. S.JungH. A.ChoiJ. S. (2017). α-Methyl Artoflavanocoumarin from Juniperus Chinensis Exerts Anti-diabetic Effects by Inhibiting PTP1B and Activating the PI3K/Akt Signaling Pathway in Insulin-Resistant HepG2 Cells. Arch. Pharm. Res.40, 1403–1413. 10.1007/s12272-017-0992-0

  • CrossRef
  • Google Scholar

• 65

  KasanganaP. B.EidH. M.NacharA.StevanovicT.HaddadP. S. (2019). Further Isolation and Identification of Anti-diabetic Principles from Root Bark of Myrianthus Arboreus P. Beauv.: The Ethyl Acetate Fraction Contains Bioactive Phenolic Compounds that Improve Liver Cell Glucose Homeostasis. J. Ethnopharmacol.245, 112167. 10.1016/j.jep.2019.112167

  • CrossRef
  • Google Scholar

• 66

  KasanganaP. B.NacharA.EidH. M.StevanovicT.HaddadP. S. (2018). Root Bark Extracts of Myrianthus Arboreus P. Beauv. (Cecropiaceae) Exhibit Anti-diabetic Potential by Modulating Hepatocyte Glucose Homeostasis. J. Ethnopharmacol.211, 117–125. 10.1016/j.jep.2017.09.017

  • CrossRef
  • Google Scholar

• 67

  KennerK. A.AnyanwuE.OlefskyJ. M.KusariJ. (1996). Protein-tyrosine Phosphatase 1B Is a Negative Regulator of Insulin- and Insulin-like Growth Factor-I-Stimulated Signaling. J. Biol. Chem.271, 19810–19816. 10.1074/jbc.271.33.19810

  • CrossRef
  • Google Scholar

• 68

  KhanalP.PatilB. M. (2021). Integration of Network and Experimental Pharmacology to Decipher the Antidiabetic Action of Duranta Repens L. J. Integr. Med.19, 66–77. 10.1016/j.joim.2020.10.003

  • CrossRef
  • Google Scholar

• 69

  KimD. H.JungH. A.SohnH. S.KimJ. W.ChoiJ. S. (2017a). Potential of Icariin Metabolites from Epimedium Koreanum Nakai as Antidiabetic Therapeutic Agents. Molecules22. 10.3390/molecules22060986

  • CrossRef
  • Google Scholar

• 70

  KimD. H.LeeS.ChungY. W.KimB. M.KimH.KimK.et al (2016). Antiobesity and Antidiabetes Effects of a Cudrania Tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential. Biomed. Res. Int.2016, 8432759. 10.1155/2016/8432759

  • CrossRef
  • Google Scholar

• 71

  KimD. H.PaudelP.YuT.NgoT. M.KimJ. A.JungH. A.et al(2017b). Characterization of the Inhibitory Activity of Natural Tanshinones from Salvia Miltiorrhiza Roots on Protein Tyrosine Phosphatase 1B. Chem. Biol. Interact.278, 65–73. 10.1016/j.cbi.2017.10.013

  • CrossRef
  • Google Scholar

• 72

  KlamanL. D.BossO.PeroniO. D.KimJ. K.MartinoJ. L.ZabolotnyJ. M.et al (2000). Increased Energy Expenditure, Decreased Adiposity, and Tissue-specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice. Mol. Cel. Biol.20, 5479–5489. 10.1128/mcb.20.15.5479-5489.2000

  • CrossRef
  • Google Scholar

• 73

  KowalczukA.BourebabaN.Kornicka-GarbowskaK.TurlejE.MaryczK.BourebabaL. (2021). Hyoscyamus Albus Nortropane Alkaloids Reduce Hyperglycemia and Hyperinsulinemia Induced in HepG2 Cells through the Regulation of SIRT1/NF-kB/JNK Pathway. Cell Commun. Signal.19, 61. 10.1186/s12964-021-00735-w

  • CrossRef
  • Google Scholar

• 74

  KrishnasamyR.PeriyasamyS. (2019). Regulating Role of Ethyl Acetate Fraction of Tephrosia Tinctoria Pers. In Carbohydrate Metabolism and Oxidative Stress in Diabetic Rats. Biomed. Pharmacother.114, 108842. 10.1016/j.biopha.2019.108842

  • CrossRef
  • Google Scholar

• 75

  KrookA.BjörnholmM.GaluskaD.JiangX. J.FahlmanR.MyersM. G.et al (2000). Characterization of Signal Transduction and Glucose Transport in Skeletal Muscle from Type 2 Diabetic Patients. Diabetes49, 284–292. 10.2337/diabetes.49.2.284

  • CrossRef
  • Google Scholar

• 76

  KurupS. B.MiniS. (2017). Protective Potential of Averrhoa Bilimbi Fruits in Ameliorating the Hepatic Key Enzymes in Streptozotocin-Induced Diabetic Rats. Biomed. Pharmacother.85, 725–732. 10.1016/j.biopha.2016.11.088

  • CrossRef
  • Google Scholar

• 77

  LangG. Z.LiC. J.GaohuT. Y.LiC.MaJ.YangJ. Z.et al (2020). Bioactive Flavonoid Dimers from Chinese Dragon's Blood, the Red Resin of Dracaena Cochinchinensis. Bioorg. Chem.97, 103659. 10.1016/j.bioorg.2020.103659

  • CrossRef
  • Google Scholar

• 78

  LeD. D.NguyenD. H.ZhaoB. T.SeongS. H.ChoiJ. S.KimS. K.et al (2017). PTP1B Inhibitors from Selaginella Tamariscina (Beauv.) Spring and Their Kinetic Properties and Molecular Docking Simulation. Bioorg. Chem.72, 273–281. 10.1016/j.bioorg.2017.05.001

  • CrossRef
  • Google Scholar

• 79

  LeeS. Y.LaiF. Y.ShiL. S.ChouY. C.YenI. C.ChangT. C. (2015). Rhodiola Crenulata Extract Suppresses Hepatic Gluconeogenesis via Activation of the AMPK Pathway. Phytomedicine22, 477–486. 10.1016/j.phymed.2015.01.016

  • CrossRef
  • Google Scholar

• 80

  LeiC.ZhangL.-B.YangJ.GaoL.-X.LiJ.-Y.LiJ.et al (2016). Macdentichalcone, a Unique Polycyclic Dimeric Chalcone from Macaranga Denticulata. Tetrahedron Lett.57, 5475–5478. 10.1016/j.tetlet.2016.10.090

  • CrossRef
  • Google Scholar

• 81

  LiB.FuR.TanH.ZhangY.TengW.LiZ.et al (2021). Characteristics of the Interaction Mechanisms of Procyanidin B1 and Procyanidin B2 with Protein Tyrosine phosphatase-1B: Analysis by Kinetics, Spectroscopy Methods and Molecular Docking. Spectrochimica Acta A: Mol. Biomol. Spectrosc.259, 119910. 10.1016/j.saa.2021.119910

  • CrossRef
  • Google Scholar

• 82

  LiC.LiC. J.MaJ.ChenF. Y.LiL.WangX. L.et al (2018a). Magterpenoids A-C, Three Polycyclic Meroterpenoids with PTP1B Inhibitory Activity from the Bark of Magnolia Officinalis Var. Biloba. Org. Lett.20, 3682–3686. 10.1021/acs.orglett.8b01476

  • CrossRef
  • Google Scholar

• 83

  LiC.LiC. J.MaJ.HuangJ. W.WangX. Y.WangX. L.et al (2019a). Magmenthanes A-H: Eight New Meroterpenoids from the Bark of Magnolia Officinalis Var. Biloba. Bioorg. Chem.88, 102948. 10.1016/j.bioorg.2019.102948

  • CrossRef
  • Google Scholar

• 84

  LiC.LiC. J.XuK. L.MaJ.HuangJ. W.YeF.et al (2020a). Novel Oligomeric Neolignans with PTP1B Inhibitory Activity from the Bark of Magnolia Officinalis Var. Biloba. Bioorg. Chem.104, 104319. 10.1016/j.bioorg.2020.104319

  • CrossRef
  • Google Scholar

• 85

  LiF.LiY.LiQ.ShiX. (2020b). Eriobotrya Japonica Leaf Triterpenoid Acids Ameliorate Metabolic Syndrome in C57BL/6J Mice Fed with High-Fat Diet. Biomed. Pharmacother.132, 110866. 10.1016/j.biopha.2020.110866

  • CrossRef
  • Google Scholar

• 86

  LiJ.YuH.WangS.WangW.ChenQ.MaY.et al (2018b). Natural Products, an Important Resource for Discovery of Multitarget Drugs and Functional Food for Regulation of Hepatic Glucose Metabolism. Drug Des. Devel. Ther.12, 121–135. 10.2147/DDDT.S151860

  • CrossRef
  • Google Scholar

• 87

  LiJ. L.LiN.XingS. S.ZhangN.LiB. B.ChenJ. G.et al (2017). New Neo-Lignan from Acanthopanax Senticosus with Protein Tyrosine Phosphatase 1B Inhibitory Activity. Arch. Pharm. Res.40, 1265–1270. 10.1007/s12272-015-0659-7

  • CrossRef
  • Google Scholar

• 88

  LiW.PuZ.YiW.MaQ.LinQ.ZhongG.et al (2019b). Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus Styracifolius. Planta Med.85, 1263–1274. 10.1055/a-1013-1417

  • CrossRef
  • Google Scholar

• 89

  LiX.XiaH.WangL.XiaG.QuY.ShangX.et al (2019c). Lignans from the Twigs of Litsea Cubeba and Their Bioactivities. Molecules24. 10.3390/molecules24020306

  • CrossRef
  • Google Scholar

• 90

  LiZ. H.GuoH.XuW. B.GeJ.LiX.AlimuM.et al (2016). Rapid Identification of Flavonoid Constituents Directly from PTP1B Inhibitive Extract of Raspberry (Rubus Idaeus L.) Leaves by HPLC-ESI-QTOF-MS-MS. J. Chromatogr. Sci.54, 805–810. 10.1093/chromsci/bmw016

  • CrossRef
  • Google Scholar

• 91

  LiangC.StaerkD.KongstadK. T. (2020). Potential of Myrtus Communis Linn. As a Bifunctional Food: Dual High-Resolution PTP1B and α-glucosidase Inhibition Profiling Combined with HPLC-HRMS and NMR for Identification of Antidiabetic Triterpenoids and Phloroglucinol Derivatives. J. Funct. Foods64, 103623. 10.1016/j.jff.2019.103623

  • CrossRef
  • Google Scholar

• 92

  LiaoZ.ZhangJ.LiuB.YanT.XuF.XiaoF.et al (2019). Polysaccharide from Okra (Abelmoschus Esculentus (L.) Moench) Improves Antioxidant Capacity via PI3K/AKT Pathways and Nrf2 Translocation in a Type 2 Diabetes Model. Molecules24, 1906. 10.3390/molecules24101906

  • CrossRef
  • Google Scholar

• 93

  LinG. M.ChenY. H.YenP. L.ChangS. T. (2016). Antihyperglycemic and Antioxidant Activities of Twig Extract from Cinnamomum Osmophloeum. J. Tradit. Complement. Med.6, 281–288. 10.1016/j.jtcme.2015.08.005

  • CrossRef
  • Google Scholar

• 94

  LinY.KuangY.LiK.WangS.SongW.QiaoX.et al (2017). Screening for Bioactive Natural Products from a 67-compound Library of Glycyrrhiza Inflata. Bioorg. Med. Chem.25, 3706–3713. 10.1016/j.bmc.2017.05.009

  • CrossRef
  • Google Scholar

• 95

  LiuY.WangC.LiJ.MeiY.LiangY. (2019). Hypoglycemic and Hypolipidemic Effects of Phellinus Linteus Mycelial Extract from Solid-State Culture in A Rat Model of Type 2 Diabetes. Nutrients11, 296. 10.3390/nu11020296

  • CrossRef
  • Google Scholar

• 96

  LiuY. P.LiY. J.ZhaoY. Y.GuoJ. M.LiuY. Y.WangX. P.et al (2021). Carbazole Alkaloids from the Fruits of Clausena Anisum-Olens with Potential PTP1B and α-glucosidase Inhibitory Activities. Bioorg. Chem.110, 104775. 10.1016/j.bioorg.2021.104775

  • CrossRef
  • Google Scholar

• 97

  LiuZ.ChengZ.HeQ.LinB.GaoP.LiL.et al (2016). Secondary Metabolites from the Flower Buds of Lonicera japonica and Their In Vitro Anti-diabetic Activities. Fitoterapia110, 44–51. 10.1016/j.fitote.2016.02.011

  • CrossRef
  • Google Scholar

• 98

  MaQ.WeiR.WangZ.LiuW.SangZ.LiY.et al (2017). Bioactive Alkaloids from the Aerial Parts of Houttuynia Cordata. J. Ethnopharmacol.195, 166–172. 10.1016/j.jep.2016.11.013

  • CrossRef
  • Google Scholar

• 99

  ManimegalaiS.MahboobS.Al-GhanimK. A.Al-MisnedF.GovindarajanM.AnbarasuK.et al (2020). Down-regulation of Hepatic G-6-Pase Expression in Hyperglycemic Rats: Intervention with Biogenic Gold Nanoconjugate. Saudi J. Biol. Sci.27, 3334–3341. 10.1016/j.sjbs.2020.09.026

  • CrossRef
  • Google Scholar

• 100

  MarvibaigiM.HosseiniS. M.AminiN. (2021). Launaea Acanthodes (Boiss) O. Kuntze Mediates Hepatic Glucose Metabolism and Ameliorates Impaired Pancreatic Function in Streptozotocin-Induced Diabetic Rats. J. Ethnopharmacol.268, 113577. 10.1016/j.jep.2020.113577

  • CrossRef
  • Google Scholar

• 101

  Mata-TorresG.Andrade-CettoA.Espinoza-HernándezF. A.Cárdenas-VázquezR. (2020). Hepatic Glucose Output Inhibition by Mexican Plants Used in the Treatment of Type 2 Diabetes. Front. Pharmacol.11, 215–219. 10.3389/fphar.2020.00215

  • CrossRef
  • Google Scholar

• 102

  MengY.DingL.WangY.NieQ. T.XingY. Y.RenQ. (2020). Phytochemical Identification of Lithocarpus Polystachyus Extracts by Ultra-high-performance Liquid Chromatography-Quadrupole Time-Of-Flight-MS and Their Protein Tyrosine Phosphatase 1B and α-glucosidase Activities. Biomed. Chromatogr.34, e4705. 10.1002/bmc.4705

  • CrossRef
  • Google Scholar

• 103

  MeyerovitchJ.BackerJ. M.KahnC. R. (1989). Hepatic Phosphotyrosine Phosphatase Activity and its Alterations in Diabetic Rats. J. Clin. Invest.84, 976–983. 10.1172/JCI114261

  • CrossRef
  • Google Scholar

• 104

  MlinarB.MarcJ.JanezA.PfeiferM. (2007). Molecular Mechanisms of Insulin Resistance and Associated Diseases. Clin. Chim. Acta375, 20–35. 10.1016/j.cca.2006.07.005

  • CrossRef
  • Google Scholar

• 105

  MohanasundaramS.RangarajanN.SampathV.PorkodiK.PennarasiM. (2021). GC-MS and HPLC Analysis of Antiglycogenolytic and Glycogenic Compounds in Kaempferol 3-O-Gentiobioside Containing Senna alata L Leaves in Experimental Rats. Translational Metab. Syndr. Res.4, 10–17. 10.1016/j.tmsr.2021.07.001

  • CrossRef
  • Google Scholar

• 106

  MuñozE. B.Luna-VitalD. A.FornasiniM.BaldeónM. E.Gonzalez de MejiaE. (2018). Gamma-conglutin Peptides from Andean Lupin Legume (Lupinus Mutabilis Sweet) Enhanced Glucose Uptake and Reduced Gluconeogenesis In Vitro. J. Funct. Foods45, 339–347. 10.1016/j.jff.2018.04.021

  • CrossRef
  • Google Scholar

• 107

  NaB.NguyenP. H.ZhaoB. T.VoQ. H.MinB. S.WooM. H. (2016). Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity and Glucosidase Inhibitory Activity of Compounds Isolated from Agrimonia Pilosa. Pharm. Biol.54, 474–480. 10.3109/13880209.2015.1048372

  • CrossRef
  • Google Scholar

• 108

  NguyenD. H.SeoU. M.ZhaoB. T.LeD. D.SeongS. H.ChoiJ. S.et al (2017). Ellagitannin and Flavonoid Constituents from Agrimonia Pilosa Ledeb. With Their Protein Tyrosine Phosphatase and Acetylcholinesterase Inhibitory Activities. Bioorg. Chem.72, 293–300. 10.1016/j.bioorg.2017.04.017

  • CrossRef
  • Google Scholar

• 109

  NguyenD. T.ToD. C.TranT. T.TranM. H.NguyenP. H. (2021). PTP1B and α-glucosidase Inhibitors from Selaginella Rolandi-Principis and Their Glucose Uptake Stimulation. J. Nat. Med.75, 186–193. 10.1007/s11418-020-01448-z

  • CrossRef
  • Google Scholar

• 110

  NguyenP. H.JiD. J.HanY. R.ChoiJ. S.RhyuD. Y.MinB. S.et al (2015). Selaginellin and Biflavonoids as Protein Tyrosine Phosphatase 1B Inhibitors from Selaginella Tamariscina and Their Glucose Uptake Stimulatory Effects. Bioorg. Med. Chem.23, 3730–3737. 10.1016/j.bmc.2015.04.007

  • CrossRef
  • Google Scholar

• 111

  NguyenP. H.TuanH. N.HoangD. T.VuQ. T.PhamM. Q.TranM. H.et al (2019). Glucose Uptake Stimulatory and PTP1B Inhibitory Activities of Pimarane Diterpenes from Orthosiphon Stamineus Benth. Biomolecules9, 859. 10.3390/biom9120859

  • CrossRef
  • Google Scholar

• 112

  NiuS. L.TongZ. F.ZhangY.LiuT. L.TianC. L.ZhangD. X.et al (2020). Novel Protein Tyrosine Phosphatase 1B Inhibitor-Geranylated Flavonoid from Mulberry Leaves Ameliorates Insulin Resistance. J. Agric. Food Chem.68, 8223–8231. 10.1021/acs.jafc.0c02720

  • CrossRef
  • Google Scholar

• 113

  NumonovS.EdirsS.BobakulovK.QureshiM. N.BozorovK.SharopovF.et al (2017). Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium Collinum Root Extracts-Computational and Experimental Investigations. Molecules22. 10.3390/molecules22060983

  • CrossRef
  • Google Scholar

• 114

  OjoO. A. (2021). Puerarin as a Potential Drug Candidate for the Management of Type-2 Diabetes: Molecular Docking and Pharmacophore Modeling Studies. Biointerface Res. Appl. Chem.11, 8751–8759. 10.33263/BRIAC112.87518759

  • CrossRef
  • Google Scholar

• 115

  Ovalle-MagallanesB.NavarreteA.HaddadP. S.TovarA. R.NoriegaL. G.Tovar-PalacioC.et al (2019). Multi-target Antidiabetic Mechanisms of Mexicanolides from Swietenia Humilis. Phytomedicine58, 152891. 10.1016/j.phymed.2019.152891

  • CrossRef
  • Google Scholar

• 116

  PageM. J.MoherD.BossuytP. M.BoutronI.HoffmannT. C.MulrowC. D.et al (2021). PRISMA 2020 Explanation and Elaboration: Updated Guidance and Exemplars for Reporting Systematic Reviews. BMJ372, n160. 10.1136/bmj.n160

  • CrossRef
  • Google Scholar

• 117

  ParveenA.FarooqM. A.KyunnW. W. (2020). A New Oleanane Type Saponin from the Aerial Parts of Nigella Sativa with Anti-oxidant and Anti-diabetic Potential. Molecules25, 1–13. 10.3390/molecules25092171

  • CrossRef
  • Google Scholar

• 118

  PedersenH. A.NdiC.SempleS. J.BuirchellB.MøllerB. L.StaerkD. (2020). PTP1B-Inhibiting Branched-Chain Fatty Acid Dimers from Eremophila Oppositifolia Subsp. Angustifolia Identified by High-Resolution PTP1B Inhibition Profiling and HPLC-PDA-HRMS-SPE-NMR Analysis. J. Nat. Prod.83, 1598–1610. 10.1021/acs.jnatprod.0c00070

  • CrossRef
  • Google Scholar

• 119

  PhamH. T. T.RyuB.ChoH. M.LeeB. W.YangW. Y.ParkE. J.et al (2020). Oleanane Hemiacetal Glycosides from Gymnema Latifolium and Their Inhibitory Effects on Protein Tyrosine Phosphatase 1B. Phytochemistry170, 112181. 10.1016/j.phytochem.2019.112181

  • CrossRef
  • Google Scholar

• 120

  PitschmannA.ZehlM.HeissE.PurevsurenS.UrbanE.DirschV. M.et al (2016). Quantitation of Phenylpropanoids and Iridoids in Insulin-Sensitising Extracts of Leonurus Sibiricus L. (Lamiaceae). Phytochem. Anal.27, 23–31. 10.1002/pca.2583

  • CrossRef
  • Google Scholar

• 121

  PompermaierL.HeissE. H.AlilouM.MayrF.MoniziM.LautenschlaegerT.et al (2018). Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia Sanguinea and Their In Vitro PTP1B Inhibitory Activities. J. Nat. Prod.81, 2091–2100. 10.1021/acs.jnatprod.8b00450

  • CrossRef
  • Google Scholar

• 122

  PosticC.DentinR.GirardJ. (2004). Role of the Liver in the Control of Carbohydrate and Lipid Homeostasis. Diabetes Metab.30, 398–408. 10.1016/S1262-3636(07)70133-7

  • CrossRef
  • Google Scholar

• 123

  QinN. B.JiaC. C.XuJ.LiD. H.XuF. X.BaiJ.et al (2017). New Amides from Seeds of Silybum marianum with Potential Antioxidant and Antidiabetic Activities. Fitoterapia119, 83–89. 10.1016/j.fitote.2017.04.008

  • CrossRef
  • Google Scholar

• 124

  QuangT. H.NganN. T.YoonC. S.ChoK. H.KangD. G.LeeH. S.et al (2015). Protein Tyrosine Phosphatase 1B Inhibitors from the Roots of Cudrania Tricuspidata. Molecules20, 11173–11183. 10.3390/molecules200611173

  • CrossRef
  • Google Scholar

• 125

  QureshiM. N.NumonovS.AisaH. A. (2019). Chemical and Pharmacological Evaluation of Hulls of Prunus Dulcis Nuts. Int. J. Anal. Chem.2019, 5861692. 10.1155/2019/5861692

  • CrossRef
  • Google Scholar

• 126

  ReddyA. S.ZhangS. (2013). Polypharmacology: Drug Discovery for the Future. Expert Rev. Clin. Pharmacol.6, 41–47. 10.1586/ECP.12.74

  • CrossRef
  • Google Scholar

• 127

  RenC.ZhangY.CuiW.LuG.WangY.GaoH.et al (2015). A Polysaccharide Extract of mulberry Leaf Ameliorates Hepatic Glucose Metabolism and Insulin Signaling in Rats with Type 2 Diabetes Induced by High Fat-Diet and Streptozotocin. Int. J. Biol. Macromol.72, 951–959. 10.1016/j.ijbiomac.2014.09.060

  • CrossRef
  • Google Scholar

• 128

  RiyaM. P.AntuK. A.PalS.ChandrakanthK. C.AnilkumarK. S.TamrakarA. K.et al (2015). Antidiabetic Property of Aerva Lanata (L.) Juss. Ex Schult. Is Mediated by Inhibition of Alpha Glucosidase, Protein Glycation and Stimulation of Adipogenesis. J. Diabetes7, 548–561. 10.1111/1753-0407.12216

  • CrossRef
  • Google Scholar

• 129

  RizzaR. A. (2010). Pathogenesis of Fasting and Postprandial Hyperglycemia in Type 2 Diabetes: Implications for Therapy. Diabetes59, 2697–2707. 10.2337/db10-1032

  • CrossRef
  • Google Scholar

• 130

  RothmanD. L.MagnussonI.KatzL. D.ShulmanR. G.ShulmanG. I. (1991). Quantitation of Hepatic Glycogenolysis and Gluconeogenesis in Fasting Humans with 13C NMR. Science254, 573–576. 10.1126/science.1948033

  • CrossRef
  • Google Scholar

• 131

  RozenbergK.RosenzweigT. (2018). Sarcopoterium Spinosum Extract Improved Insulin Sensitivity in Mice Models of Glucose Intolerance and Diabetes. PLoS One13, e0196736. 10.1371/journal.pone.0196736

  • CrossRef
  • Google Scholar

• 132

  RyuB.ChoH. M.ZhangM.LeeB. W.DoanT. P.ParkE. J.et al (2021). Meroterpenoids from the Leaves of Psidium Guajava (Guava) Cultivated in Korea Using MS/MS-based Molecular Networking. Phytochemistry186, 112723. 10.1016/j.phytochem.2021.112723

  • CrossRef
  • Google Scholar

• 133

  SaadeldeenF. S. A.NiuY.WangH.ZhouL.MengL.ChenS.et al (2020). Natural Products: Regulating Glucose Metabolism and Improving Insulin Resistance. Food Sci. Hum. Wellness9, 214–228. 10.1016/j.fshw.2020.04.005

  • CrossRef
  • Google Scholar

• 134

  SaetingO.ChandarajotiK.PhongphisutthinanA.HongsprabhasP.Sae-TanS. (2021). Water Extract of Mungbean (Vigna Radiata L.) Inhibits Protein Tyrosine Phosphatase-1B in Insulin-Resistant HepG2 Cells. Molecules26, 1452. 10.3390/molecules26051452

  • CrossRef
  • Google Scholar

• 135

  SaiC.-M.QinN.-B.JiaC.-C.LiD.-H.WangK.-B.PeiY.-H.et al (2016). Macleayine, a New Alkaloid from Macleaya Cordata. Chin. Chem. Lett.27, 1717–1720. 10.1016/j.cclet.2016.06.017

  • CrossRef
  • Google Scholar

• 136

  SaifudinA.LalloS. A.TezukaY. (2016a). The Potent Inhibitors of Protein Tyrosine Phosphatase 1B from the Fruits of Melaleuca Leucadendron. Pharmacognosy Res.8, S38–S41. 10.4103/0974-8490.178644

  • CrossRef
  • Google Scholar

• 137

  SaifudinA.UsiaT.AbLalloS.MoritaH.TanakaK.TezukaY. (2016b). Potent Water Extracts of Indonesian Medicinal Plants against PTP1B. Asian Pac. J. Trop. Biomed.6, 38–43. 10.1016/j.apjtb.2015.09.021

  • CrossRef
  • Google Scholar

• 138

  Salinas-ArellanoE.Pérez-VásquezA.Rivero-cruzI.Torres-ColinR.González-AndradeM.Rangel-GrimaldoM.et al (2020). Flavonoids and Terpenoids with PTP-1B Inhibitory Properties from the Infusion of Salvia Amarissima Ortega. Molecules25, 1–18. 10.3390/molecules25153530

  • CrossRef
  • Google Scholar

• 139

  SaltielA. R.KahnC. R. (2001). Insulin Signalling and the Regulation of Glucose and Lipid Metabolism. Nature414, 799–806. 10.1038/414799a

  • CrossRef
  • Google Scholar

• 140

  SawantL.SinghV. K.DetheS.BhaskarA.BalachandranJ.MundkinajedduD.et al (2015). Aldose Reductase and Protein Tyrosine Phosphatase 1B Inhibitory Active Compounds from Syzygium Cumini Seeds. Pharm. Biol.53, 1176–1182. 10.3109/13880209.2014.967784

  • CrossRef
  • Google Scholar

• 141

  SchultzeS. M.HemmingsB. A.NiessenM.TschoppO. (2012). PI3K/AKT, MAPK and AMPK Signalling: Protein Kinases in Glucose Homeostasis. Expert Rev. Mol. Med.14, e1–21. 10.1017/S1462399411002109

  • CrossRef
  • Google Scholar

• 142

  SelvarajG.KaliamurthiS.ThirugnasambandanR. (2016). Effect of Glycosin Alkaloid from Rhizophora apiculata in Non-insulin Dependent Diabetic Rats and its Mechanism of Action: In Vivo and In Silico Studies. Phytomedicine23, 632–640. 10.1016/j.phymed.2016.03.004

  • CrossRef
  • Google Scholar

• 143

  SemaanD. G.IgoliJ. O.YoungL.GrayA. I.RowanE. G.MarreroE. (2018). In Vitro anti-diabetic Effect of Flavonoids and Pheophytins from Allophylus Cominia Sw. On the Glucose Uptake Assays by HepG2, L6, 3T3-L1 and Fat Accumulation in 3T3-L1 Adipocytes. J. Ethnopharmacol.216, 8–17. 10.1016/j.jep.2018.01.014

  • CrossRef
  • Google Scholar

• 144

  SemaanD. G.IgoliJ. O.YoungL.MarreroE.GrayA. I.RowanE. G. (2017). In Vitro anti-diabetic Activity of Flavonoids and Pheophytins from Allophylus Cominia Sw . On PTP1B, DPPIV, Alpha-Glucosidase and Alpha-Amylase Enzymes. J. Ethnopharmacol.203, 39–46. 10.1016/j.jep.2017.03.023

  • CrossRef
  • Google Scholar

• 145

  SeoY. S.ShonM. Y.KongR.KangO. H.ZhouT.KimD. Y.et al (2016). Black Ginseng Extract Exerts Anti-hyperglycemic Effect via Modulation of Glucose Metabolism in Liver and Muscle. J. Ethnopharmacol.190, 231–240. 10.1016/j.jep.2016.05.060

  • CrossRef
  • Google Scholar

• 146

  SeongS. H.RoyA.JungH. A.JungH. J.ChoiJ. S. (2016). Protein Tyrosine Phosphatase 1B and α-glucosidase Inhibitory Activities of Pueraria Lobata Root and its Constituents. J. Ethnopharmacol.194, 706–716. 10.1016/j.jep.2016.10.007

  • CrossRef
  • Google Scholar

• 147

  SharabiK.TavaresC. D.RinesA. K.PuigserverP. (2015). Molecular Pathophysiology of Hepatic Glucose Production. Mol. Aspects Med.46, 21–33. 10.1016/j.mam.2015.09.003

  • CrossRef
  • Google Scholar

• 148

  SiqueiraJ. T.BatistelaE.PereiraM. P.da SilvaV. C.de Sousa JuniorP. T.AndradeC. M.et al (2016). Combretum Lanceolatum Flowers Ethanol Extract Inhibits Hepatic Gluconeogenesis: an In Vivo Mechanism Study. Pharm. Biol.54, 1671–1679. 10.3109/13880209.2015.1120321

  • CrossRef
  • Google Scholar

• 149

  SuC.DuanY.TianJ.LiuJ.XieK.ChenD.et al (2020). Morusalisins A-F, Six New Diels-Alder Type Adducts, as Potential PTP1B Inhibitors from Cell Cultures of Morus alba. Fitoterapia146, 104682. 10.1016/j.fitote.2020.104682

  • CrossRef
  • Google Scholar

• 150

  SuC.TaoX.YinZ.ZhangX.TianJ.ChenR.et al (2019). Morusalones A-D, Diels-Alder Adducts with 6/7/6/6/6/6 Hexacyclic Ring Systems as Potential PTP1B Inhibitors from Cell Cultures of Morus alba. Org. Lett.21, 9463–9467. 10.1021/acs.orglett.9b03664

  • CrossRef
  • Google Scholar

• 151

  SunJ.WangY.FuX.ChenY.WangD.LiW.et al (2015). Magnolia Officinalis Extract Contains Potent Inhibitors against PTP1B and Attenuates Hyperglycemia in Db/db Mice. Biomed. Res. Int.2015, 139451. 10.1155/2015/139451

  • CrossRef
  • Google Scholar

• 152

  SunJ.QuC.WangY.HuangH.ZhangM.LiH.et al (2018). PTP1B, A Potential Target of Type 2 Diabetes Mellitus. Mol. Biol.05. 10.4172/2168-9547.1000174

  • CrossRef
  • Google Scholar

• 153

  SunR.DengX.ZhangD.XieF.WangD.WangJ.et al (2019). Anti-diabetic Potential of Pueraria Lobata Root Extract through Promoting Insulin Signaling by PTP1B Inhibition. Bioorg. Chem.87, 12–15. 10.1016/j.bioorg.2019.02.046

  • CrossRef
  • Google Scholar

• 154

  SurekaC.ElangoV.Al-GhamdiS.AldossariK. K.AlsaidanM.GeddawyA.et al (2021). Ameliorative Property of Sesbania Grandiflora on Carbohydrate Metabolic Enzymes in the Liver and Kidney of Streptozotocin-Induced Diabetic Rats. Saudi J. Biol. Sci.28, 3669–3677. 10.1016/j.sjbs.2021.05.002

  • CrossRef
  • Google Scholar

• 155

  TahtahY.WubshetS. G.KongstadK. T.HeskesA. M.PaterakiI.MøllerB. L.et al (2016). High-resolution PTP1B Inhibition Profiling Combined with High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry-solid-phase Extraction-Nuclear Magnetic Resonance Spectroscopy: Proof-Of-Concept and Antidiabetic Constituents in Crude Extract of Eremophila Lucida. Fitoterapia110, 52–58. 10.1016/j.fitote.2016.02.008

  • CrossRef
  • Google Scholar

• 156

  TangD.ChenQ. B.XinX. L.AisaH. A. (2017). Anti-diabetic Effect of Three New Norditerpenoid Alkaloids In Vitro and Potential Mechanism via PI3K/Akt Signaling Pathway. Biomed. Pharmacother.87, 145–152. 10.1016/j.biopha.2016.12.058

  • CrossRef
  • Google Scholar

• 157

  TianJ. L.LiaoX. J.WangY. H.SiX.ShuC.GongE. S.et al (2019). Identification of Cyanidin-3-Arabinoside Extracted from Blueberry as a Selective Protein Tyrosine Phosphatase 1B Inhibitor. J. Agric. Food Chem.67, 13624–13634. 10.1021/acs.jafc.9b06155

  • CrossRef
  • Google Scholar

• 158

  TianJ. Y.TaoR. Y.ZhangX. L.LiuQ.HeY. B.SuY. L.et al (2015). Effect of Hypericum perforatum L. Extract on Insulin Resistance and Lipid Metabolic Disorder in High-Fat-Diet Induced Obese Mice. Phytother. Res.29, 86–92. 10.1002/ptr.5230

  • CrossRef
  • Google Scholar

• 159

  TiongS. H.LooiC. Y.AryaA.WongW. F.HazniH.MustafaM. R.et al (2015). Vindogentianine, a Hypoglycemic Alkaloid from Catharanthus Roseus (L.) G. Don (Apocynaceae). Fitoterapia102, 182–188. 10.1016/j.fitote.2015.01.019

  • CrossRef
  • Google Scholar

• 160

  ToD. C.BuiT. Q.NhungN. T. A.TranQ. T.DoT. T.TranM. H.et al (2021). On the Inhibitability of Natural Products Isolated from Tetradium Ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study. Molecules26. 10.3390/molecules26123691

  • CrossRef
  • Google Scholar

• 161

  TonksN. K.DiltzC. D.FischerE. H. (1988). Characterization of the Major Protein-Tyrosine-Phosphatases of Human Placenta. J. Biol. Chem.263, 6731–6737. 10.1016/s0021-9258(18)68703-4

  • CrossRef
  • Google Scholar

• 162

  TrinhB. T.QuachT. T.BuiD. N.StaerkD.NguyenL. D.JägerA. K. (2017b). Xanthones from the Twigs of Garcinia Oblongifolia and Their Antidiabetic Activity. Fitoterapia118, 126–131. 10.1016/j.fitote.2017.03.003

  • CrossRef
  • Google Scholar

• 163

  TrinhB. T. D.JägerA. K.StaerkD. (2017a). High-Resolution Inhibition Profiling Combined with HPLC-HRMS-SPE-NMR for Identification of PTP1B Inhibitors from Vietnamese Plants. Molecules22. 10.3390/molecules22071228

  • CrossRef
  • Google Scholar

• 164

  UwazieJ. N.YakubuM. T.AshafaA. O. T.AjiboyeT. O. (2020). Identification and Characterization of Anti-diabetic Principle in Senna alata (Linn.) Flower Using Alloxan-Induced Diabetic Male Wistar Rats. J. Ethnopharmacol.261, 112997. 10.1016/j.jep.2020.112997

  • CrossRef
  • Google Scholar

• 165

  VoQ. H.NguyenP. H.ZhaoB. T.AliM. Y.ChoiJ. S.MinB. S.et al (2015). Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Constituents from the Aerial Parts of Tradescantia Spathacea Sw. Fitoterapia103, 113–121. 10.1016/j.fitote.2015.03.017

  • CrossRef
  • Google Scholar

• 166

  VuN. K.KimC. S.HaM. T.NgoQ. T.ParkS. E.KwonH.et al (2020). Antioxidant and Antidiabetic Activities of Flavonoid Derivatives from the Outer Skins of Allium cepa L. J. Agric. Food Chem.68, 8797–8811. 10.1021/acs.jafc.0c02122

  • CrossRef
  • Google Scholar

• 167

  WangH.GuD.WangM.GuoH.WuH.TianG.et al (2017a). A Strategy Based on Gas Chromatography-Mass Spectrometry and Virtual Molecular Docking for Analysis and Prediction of Bioactive Composition in Natural Product Essential Oil. J. Chromatogr. A.1501, 128–133. 10.1016/j.chroma.2017.04.031

  • CrossRef
  • Google Scholar

• 168

  WangJ.HuangY.LiK.ChenY.VanegasD.McLamoreE. S.et al (2016a). Leaf Extract from Lithocarpus Polystachyus Rehd. Promote Glycogen Synthesis in T2DM Mice. PLoS One11, e0166557. 10.1371/journal.pone.0166557

  • CrossRef
  • Google Scholar

• 169

  WangJ.YangJ. L.ZhouP. P.MengX. H.ShiY. P. (2017b). Further New Gypenosides from Jiaogulan (Gynostemma Pentaphyllum). J. Agric. Food Chem.65, 5926–5934. 10.1021/acs.jafc.7b01477

  • CrossRef
  • Google Scholar

• 170

  WangL.-J.XiongJ.ZouY.MeiQ.-B.WangW.-X.HuJ.-F. (2016b). Sesquiterpenoids from the Chinese Endangered Plant Manglietia Aromatica. Phytochemistry Lett.18, 202–207. 10.1016/j.phytol.2016.10.018

  • CrossRef
  • Google Scholar

• 171

  WangM.YuB. W.YuM. H.GaoL. X.LiJ. Y.WangH. Y.et al (2015). New Isoprenylated Phenolic Compounds from Morus Laevigata. Chem. Biodivers.12, 937–945. 10.1002/cbdv.201400210

  • CrossRef
  • Google Scholar

• 172

  WuY.OuyangJ. P.WuK.WangS. S.WenC. Y.XiaZ. Y. (2005). Rosiglitazone Ameliorates Abnormal Expression and Activity of Protein Tyrosine Phosphatase 1B in the Skeletal Muscle of Fat-Fed, Streptozotocin-Treated Diabetic Rats. Br. J. Pharmacol.146, 234–243. 10.1038/sj.bjp.0706306

  • CrossRef
  • Google Scholar

• 173

  XiaoT.GuoZ.SunB.ZhaoY. (2017b). Identification of Anthocyanins from Four Kinds of Berries and Their Inhibition Activity to α-Glycosidase and Protein Tyrosine Phosphatase 1B by HPLC-FT-ICR MS/MS. J. Agric. Food Chem.65, 6211–6221. 10.1021/acs.jafc.7b02550

  • CrossRef
  • Google Scholar

• 174

  XiaoT.GuoZ.BiX.ZhaoY. (2017a). Polyphenolic Profile as Well as Anti-oxidant and Anti-diabetes Effects of Extracts from Freeze-Dried Black Raspberries. J. Funct. Foods31, 179–187. 10.1016/j.jff.2017.01.038

  • CrossRef
  • Google Scholar

• 175

  XiongJ.HuC. L.WangP. P.GaoD. D.HuangF.LiJ.et al (2020). Spirobiflavonoid Stereoisomers from the Endangered conifer Glyptostrobus Pensilis and Their Protein Tyrosine Phosphatase 1B Inhibitory Activity. Bioorg. Med. Chem. Lett.30, 126943. 10.1016/j.bmcl.2019.126943

  • CrossRef
  • Google Scholar

• 176

  XiongJ.WanJ.DingJ.WangP. P.MaG. L.LiJ.et al (2017). Camellianols A-G, Barrigenol-like Triterpenoids with PTP1B Inhibitory Effects from the Endangered Ornamental Plant Camellia Crapnelliana. J. Nat. Prod.80, 2874–2882. 10.1021/acs.jnatprod.7b00241

  • CrossRef
  • Google Scholar

• 177

  XuJ.WangX.YueJ.SunY.ZhangX.ZhaoY. (2018b). Polyphenols from Acorn Leaves (Quercus Liaotungensis) Protect Pancreatic Beta Cells and Their Inhibitory Activity against α-Glucosidase and Protein Tyrosine Phosphatase 1B. Molecules23. 10.3390/molecules23092167

  • CrossRef
  • Google Scholar

• 178

  XuJ.YangL.WangR.ZengK.FanB.ZhaoZ. (2019a). The Biflavonoids as Protein Tyrosine Phosphatase 1B Inhibitors from Selaginella Uncinata and Their Antihyperglycemic Action. Fitoterapia137, 104255. 10.1016/j.fitote.2019.104255

  • CrossRef
  • Google Scholar

• 179

  XuJ.CaoJ.YueJ.ZhangX.ZhaoY. (2018a). New Triterpenoids from Acorns of Quercus Liaotungensis and Their Inhibitory Activity against α -glucosidase, α -amylase and Protein-Tyrosine Phosphatase 1B. J. Funct. Foods41, 232–239. 10.1016/j.jff.2017.12.054

  • CrossRef
  • Google Scholar

• 180

  XuL.LiY.DaiY.PengJ. (2018c). Natural Products for the Treatment of Type 2 Diabetes Mellitus: Pharmacology and Mechanisms. Pharmacol. Res.130, 451–465. 10.1016/j.phrs.2018.01.015

  • CrossRef
  • Google Scholar

• 181

  XuQ. Q.ChenX. L.XuJ. F.WangS. B.LuoJ. G.KongL. Y. (2019b). Acetophenone Derivatives from the Roots of Melicope Ptelefolia. Fitoterapia132, 40–45. 10.1016/j.fitote.2018.11.013

  • CrossRef
  • Google Scholar

• 182

  YanH. W.ZhuH.YuanX.YangY. N.FengZ. M.JiangJ. S.et al (2019). Eight New Biflavonoids with Lavandulyl Units from the Roots of Sophora Flavescens and Their Inhibitory Effect on PTP1B. Bioorg. Chem.86, 679–685. 10.1016/j.bioorg.2019.01.058

  • CrossRef
  • Google Scholar

• 183

  YangJ. B.YeF.TianJ. Y.SongY. F.GaoH. Y.LiuY.et al (2020). Multiflorumisides HK, Stilbene Glucosides Isolated from Polygonum Multiflorum and Their In Vitro PTP1B Inhibitory Activities. Fitoterapia146, 104703. 10.1016/j.fitote.2020.104703

  • CrossRef
  • Google Scholar

• 184

  YangJ. L.HaT. K. Q.LeeB. W.KimJ.OhW. K. (2017). PTP1B Inhibitors from the Seeds of Iris Sanguinea and Their Insulin Mimetic Activities via AMPK and ACC Phosphorylation. Bioorg. Med. Chem. Lett.27, 5076–5081. 10.1016/j.bmcl.2017.09.031

  • CrossRef
  • Google Scholar

• 185

  YangN.ZhangS.YangS.GuoZ.ZhangX.ZhaoY. (2016). The Inhibition of α-glycosidase and Protein Tyrosine Phosphatase 1B (PTP1B) Activities by Ginsenosides from Panax Ginseng C.A. Meyer and Simultaneous Determination by HPLC-ELSD. J. Funct. Foods23, 188–197. 10.1016/j.jff.2015.12.018

  • CrossRef
  • Google Scholar

• 186

  YinX.HuangY.JungD. W.ChungH. C.ChoungS. Y.ShimJ. H.et al (2015). Anti-Diabetic Effect of Aster Sphathulifolius in C57BL/KsJ-Db/db Mice. J. Med. Food18, 987–998. 10.1089/jmf.2014.3416

  • CrossRef
  • Google Scholar

• 187

  Yousof AliM.JungH. A.ChoiJ. S. (2015). Anti-diabetic and Anti-alzheimer's Disease Activities of Angelica Decursiva. Arch. Pharm. Res.38, 2216–2227. 10.1007/s12272-015-0629-0

  • CrossRef
  • Google Scholar

• 188

  YuJ. H.LiuQ. F.ShengL.WangG. C.LiJ.YueJ. M. (2016a). Cipacinoids A-D, Four Limonoids with Spirocyclic Skeletons from Cipadessa Cinerascens. Org. Lett.18, 444–447. 10.1021/acs.orglett.5b03487

  • CrossRef
  • Google Scholar

• 189

  YuY.GanL. S.YangS. P.ShengL.LiuQ. F.ChenS. N.et al (2016b). Eucarobustols A-I, Conjugates of Sesquiterpenoids and Acylphloroglucinols from Eucalyptus Robusta. J. Nat. Prod.79, 1365–1372. 10.1021/acs.jnatprod.6b00090

  • CrossRef
  • Google Scholar

• 190

  YuanY. C.BaiX. L.LiuY. M.TangX. Y.YuanH.LiaoX. (2021). Ligand Fishing Based on Cell Surface Display of Enzymes for Inhibitor Screening. Anal. Chim. Acta1156, 338359. 10.1016/j.aca.2021.338359

  • CrossRef
  • Google Scholar

• 191

  YueJ.XuJ.CaoJ.ZhangX.ZhaoY. (2017). Cucurbitane Triterpenoids from Momordica Charantia L. And Their Inhibitory Activity against α-glucosidase, α-amylase and Protein Tyrosine Phosphatase 1B (PTP1B). J. Funct. Foods37, 624–631. 10.1016/j.jff.2017.07.041

  • CrossRef
  • Google Scholar

• 192

  Zakłos-SzydaM.PawlikN. (2018). Japanese Quince (Chaenomeles Japonica L.) Fruit Polyphenolic Extract Modulates Carbohydrate Metabolism in HepG2 Cells via AMP-Activated Protein Kinase. Acta Biochim. Pol.65, 67–78. 10.18388/abp.2017_1604

  • CrossRef
  • Google Scholar

• 193

  ZhangC. C.GengC. A.HuangX. Y.ZhangX. M.ChenJ. J. (2019a). Antidiabetic Stilbenes from Peony Seeds with PTP1B, α-Glucosidase, and DPPIV Inhibitory Activities. J. Agric. Food Chem.67, 6765–6772. 10.1021/acs.jafc.9b01193

  • CrossRef
  • Google Scholar

• 194

  ZhangP. Z.GuJ.ZhangG. L. (2015). Novel Stilbenes from Artocarpus Nanchuanensis. J. Asian Nat. Prod. Res.17, 217–223. 10.1080/10286020.2015.1006202

  • CrossRef
  • Google Scholar

• 195

  ZhangR.YuR.XuQ.LiX.LuoJ.JiangB.et al (2017). Discovery and Evaluation of the Hybrid of Bromophenol and Saccharide as Potent and Selective Protein Tyrosine Phosphatase 1B Inhibitors. Eur. J. Med. Chem.134, 24–33. 10.1016/j.ejmech.2017.04.004

  • CrossRef
  • Google Scholar

• 196

  ZhangS. N.ZengJ.TanY. N.MaR. J.ZhangG. J.WangH. S.et al (2019b). 3α,19-Dihydroxyl-ent-pimara-8(14),15-diene, a New Diterpenoid from the Rhizomes of Ricinus communis. J. Asian Nat. Prod. Res.21, 522–527. 10.1080/10286020.2018.1461087

  • CrossRef
  • Google Scholar

• 197

  ZhangW.HongD.ZhouY.ZhangY.ShenQ.LiJ. Y.et al (2006). Ursolic Acid and its Derivative Inhibit Protein Tyrosine Phosphatase 1B, Enhancing Insulin Receptor Phosphorylation and Stimulating Glucose Uptake. Biochim. Biophys. Acta1760, 1505–1512. 10.1016/j.bbagen.2006.05.009

  • CrossRef
  • Google Scholar

• 198

  ZhangX.LvQ.JiaS.ChenY.SunC.LiX.et al (2016a). Effects of flavonoid-rich Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit extract on regulating glucose and lipid metabolism in diabetic KK-A(y) mice. Food Funct.7, 3130–3140. 10.1039/c6fo00397d

  • CrossRef
  • Google Scholar

• 199

  ZhangX. Y.LiW.WangJ.LiN.ChengM. S.KoikeK. (2019c). Protein Tyrosine Phosphatase 1B Inhibitory Activities of Ursane-type Triterpenes from Chinese Raspberry, Fruits of Rubus Chingii. Chin. J. Nat. Med.17, 15–21. 10.1016/S1875-5364(19)30004-4

  • CrossRef
  • Google Scholar

• 200

  ZhangY.ChenJ.ZengY.HuangD.XuQ. (2019d). Involvement of AMPK Activation in the Inhibition of Hepatic Gluconeogenesis by Ficus Carica Leaf Extract in Diabetic Mice and HepG2 Cells. Biomed. Pharmacother.109, 188–194. 10.1016/j.biopha.2018.10.077

  • CrossRef
  • Google Scholar

• 201

  ZhangY.FengF.ChenT.LiZ.ShenQ. W. (2016b). Antidiabetic and Antihyperlipidemic Activities of Forsythia Suspensa (Thunb.) Vahl (Fruit) in Streptozotocin-Induced Diabetes Mice. J. Ethnopharmacol.192, 256–263. 10.1016/j.jep.2016.07.002

  • CrossRef
  • Google Scholar

• 202

  ZhangY.YanL. S.DingY.ChengB. C. Y.LuoG.KongJ.et al (2020). Edgeworthia Gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes. Front. Pharmacol.10, 1666. 10.3389/fphar.2019.01666

  • CrossRef
  • Google Scholar

• 203

  ZhaoB. T.LeD. D.NguyenP. H.AliM. Y.ChoiJ. S.MinB. S.et al (2016). PTP1B, α-glucosidase, and DPP-IV Inhibitory Effects for Chromene Derivatives from the Leaves of Smilax china L. Chem. Biol. Interact.253, 27–37. 10.1016/j.cbi.2016.04.012

  • CrossRef
  • Google Scholar

• 204

  ZhaoC. C.ChenJ.ShaoJ. H.ZhangX. H.GuW. Y.ShenJ.et al (2020). Lignan Constituents from the Fruits of Viburnum Macrocephalum F. Keteleeri and Their α-Amylase, α-Glucosidase, and Protein Tyrosine Phosphatase 1B Inhibitory Activities. J. Agric. Food Chem.68, 11151–11160. 10.1021/acs.jafc.0c03353

  • CrossRef
  • Google Scholar

• 205

  ZhaoY.ChenM. X.KongstadK. T.JägerA. K.StaerkD. (2017). Potential of Polygonum Cuspidatum Root as an Antidiabetic Food: Dual High-Resolution α-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-HRMS and NMR for Identification of Antidiabetic Constituents. J. Agric. Food Chem.65, 4421–4427. 10.1021/acs.jafc.7b01353

  • CrossRef
  • Google Scholar

• 206

  ZhaoY.KjaerulffL.KongstadK. T.HeskesA. M.MøllerB. L.StaerkD. (2019a). 2(5H)-Furanone Sesquiterpenes from Eremophila bignoniiflora: High-Resolution Inhibition Profiling and PTP1B Inhibitory Activity. Phytochemistry166, 112054. 10.1016/j.phytochem.2019.112054

  • CrossRef
  • Google Scholar

• 207

  ZhaoY.KongstadK. T.LiuY.HeC.StaerkD. (2019b). Unraveling the Complexity of Complex Mixtures by Combining High-Resolution Pharmacological, Analytical and Spectroscopic Techniques: Antidiabetic Constituents in Chinese Medicinal Plants. Faraday Discuss.218, 202–218. 10.1039/c8fd00223a

  • CrossRef
  • Google Scholar

• 208

  ZhaoY.KongstadK. T.JägerA. K.NielsenJ.StaerkD. (2018). Quadruple High-Resolution α-glucosidase/α-amylase/PTP1B/radical Scavenging Profiling Combined with High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry-solid-phase Extraction-Nuclear Magnetic Resonance Spectroscopy for Identification of Antidiabetic Constituents in Crude Root Bark of Morus alba L. J. Chromatogr. A1556, 55–63. 10.1016/j.chroma.2018.04.041

  • CrossRef
  • Google Scholar

• 209

  ZhengX. M.MengF. W.GengF.QiM.LuoC.YangL.et al (2015). Plantadeprate A, a Tricyclic Monoterpene Zwitterionic Guanidium, and Related Derivatives from the Seeds of Plantago Depressa. J. Nat. Prod.78, 2822–2826. 10.1021/acs.jnatprod.5b00368

  • CrossRef
  • Google Scholar

• 210

  ZhouJ.WuZ.OyawalujaB. O.CokerH. A. B.OdukoyaO. A.YaoG.et al (2019). Protein Tyrosine Phosphatase 1B Inhibitory Iridoids from Psydrax Subcordata. J. Nat. Prod.82, 2916–2924. 10.1021/acs.jnatprod.9b00770

  • CrossRef
  • Google Scholar

• 211

  ZhouX.WangL. L.TangW. J.TangB. (2021). Astragaloside IV Inhibits Protein Tyrosine Phosphatase 1B and Improves Insulin Resistance in Insulin-Resistant HepG2 Cells and Triglyceride Accumulation in Oleic Acid (OA)-treated HepG2 Cells. J. Ethnopharmacol.268, 113556. 10.1016/j.jep.2020.113556

  • CrossRef
  • Google Scholar

• 212

  ZhuY.HuangJ. J.ZhangX. X.YanY.YinX. W.PingG.et al (2018). Qing Gan Zi Shen Tang Alleviates Adipose Tissue Dysfunction with Up-Regulation of SIRT1 in Spontaneously Hypertensive Rat. Biomed. Pharmacother.105, 246–255. 10.1016/j.biopha.2018.05.022

  • CrossRef
  • Google Scholar