Skip to main content
BioMed Research International logoLink to BioMed Research International
. 2014 Apr 10;2014:798093. doi: 10.1155/2014/798093

The Antihyperglycemic Effects of Rhizoma Coptidis and Mechanism of Actions: A Review of Systematic Reviews and Pharmacological Research

Hui Wang 1, Wei Mu 1, Hongcai Shang 1,*, Jia Lin 1, Xiang Lei 1
PMCID: PMC4003828  PMID: 24818152

Abstract

Rhizoma Coptidis (Huang Lian in Chinese pinyin) is among the most widely used traditional Chinese herbal medicines and has a profound history of more than 2000 years of being used as a therapeutic herb. The antidiabetic effects of Rhizoma Coptidis have been extensively investigated in animal experiments and clinical trials and its efficacy as a promising antihyperglycemic agent has been widely discussed. In the meantime, findings from modern pharmacological studies have contributed the majority of its bioactivities to berberine, the isoquinoline alkaloids component of the herb, and a number of experiments testing the antidiabetic effects of berberine have been initiated. Therefore, we conducted a review of the current evidence profile of the antihyperglycemic effects of Rhizoma Coptidis as well as its main component berberine and the possible mechanism of actions, in order to summarize research evidence in this area and identify future research directions.

1. Introduction

Diabetes mellitus refers to a metabolic disorder of multiple etiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat, and protein metabolism resulting from disturbed insulin secretion, insulin action, or both [1]. There are two possible types of diabetes mellitus. Type 1 diabetes, also known as insulin-dependent diabetes, results from an absolute lack of insulin due to autoimmune destruction of the insulin-producing beta cells in the pancreas [2]. Type 2 or non-insulin-dependent diabetes is a metabolic disorder characterized by insulin resistance, relative insulin deficiency, and hyperglycemia [3]. Diabetes mellitus is most closely related to the wasting (Xiao Ke in Chinese pinyin) syndrome as defined by the traditional Chinese medicine diagnostic pattern. Patients with this syndrome typically experience clinical manifestations of emaciation (Xiao in Chinese) and thirst (Ke in Chinese).

According to the WHO diabetes fact sheets, 347 million people in the world have diabetes [4]. In 2004, an estimated 3.4 million people worldwide died from consequences of high blood sugar, and ca. above 80% of diabetes deaths happen in underdeveloped countries [4]. Facing this stark reality, traditional Chinese herbal remedy such as Rhizoma Coptidis (Huang Lian in Chinese pinyin), with its long proven effects for a number of chronic diseases in clinical application and relatively low cost, has been broadly investigated in Asian countries for potential antihyperglycemic effects.

Rhizoma Coptidis (Huang Lian) is the dried rhizome of Coptis chinensis Franch, Coptis deltoidea C. Y. Cheng et Hsiao or Coptis teeta Wall. As first recorded in Shennong's Materia Medica in the eastern Han dynasty (25–220 AD), the herbal medicine has been prescribed by Chinese herbalists for a variety of illnesses and conditions for more than 2000 years. According to traditional beliefs, Rhizoma Coptidis is cold in nature and bitter in taste and enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It has the function of clearing heat, drying dampness, and purging fire toxins [5]. Main indications include the wasting (Xiao Ke) syndrome, distention, and fullness due to dampness and heat, sickness, acid regurgitation, jaundice, palpitation, diarrhea caused by bacterial infection, high fever, heart-fever hyperactivity, restlessness and insomnia, blood spitting or nose bleeding due to extra heat in the blood, red eyes, and toothache [5].

As early as the Wei and Jin dynasties in the Chinese history (220–589 AD), Rhizoma Coptidis was described as a therapeutic agent for patients suffering from the wasting syndrome. In dynasties that followed, numerous records had been kept in a series of herbal classics of the medicinal use of Rhizoma Coptidis for the wasting syndrome, either alone or combined with other herbs in a formula. This proved the prevalence of the use of Rhizoma Coptidis since ancient times and formed the empirical evidence base for its antidiabetic effects. For example, in the Miscellaneous Records of Famous Physicians, compiled around 510 AD, Rhizoma Coptidis was first described as an agent for the wasting syndrome [6]. In the Newly Revised Materia Medica compiled during the Tang dynasty (618–907 AD), it was noted that “Huang lian grown in west China is bulky, bitter and good for treating the wasting syndrome” [7]. An analytical review of the Song dynasty (960–1279 AD) medical formulary Formulas from Benevolent Sages found that Rhizoma Coptidis was among the top ten most frequently used medicinal herbs in formulas designated for the wasting syndrome [8]. Furthermore, thirteen among the total of 64 herbal formulas for treating the wasting syndrome collected in the Puji Fang Prescriptions for Universal Relief, completed around 1406 AD in the Ming dynasty, contained Rhizoma Coptidis [9]. In the most comprehensive medical book of traditional Chinese medicine, the Compendium of Materia Medica, published in the same dynasty, it recorded that “Huang lian, steamed with wine, is used for treating emaciation, thirst and excessive excretion of urine” [9].

Modern pharmacological research identified the major chemical constituents of Rhizoma Coptidis to be alkaloids including berberine, coptisine, worenine, palmatine, jatrorrhizine, and epiberberine [10, 11]. Among the many constituents, the berberine component is generally considered the primary contributor to its main bioactivities such as the antibiotic, antioxidant, and anti-inflammatory properties [12]. In recent years, berberine and Rhizoma Coptidis extracts have also been reported to have multiple antidiabetic activities such as regulating lipid, balancing glucose metabolism, and improving insulin resistance, and the underlying mechanisms of action have been extensively investigated [12].

In view of this, a comprehensive review of the relevant literatures on the antihyperglycemic effects of Rhizoma Coptidis (or berberine) and the mechanism of actions was conducted. The aim of this study is to give a summary of the existing evidence.

2. Method

In January 2013 two reviewers (Hui Wang and Wei Mu) searched the following Chinese-language electronic databases: Chinese Biomedical Literature Database (CBM, 1980–2013), Chinese Journal Full-Text Database (CNKI, 1980–2013), Weipu Journal Database (VIP, 1989–2013), and Wanfang Data (1990–2013), and three English-language databases: PubMed, EMBASE (1989–2013), and the Cochrane Library. The search terms included “huang lian,” “Coptis,” “berberine,” “hypoglycemic,” “diabetes,” and “xiaoke” in English or Chinese. These terms were searched as free text in the title or the abstract.

Two reviewers Hui Wang and Wei Mu screened citations identified from electronic searches and retrieved the full texts of relevant studies. Then they summarized records in ancient medical books and the findings of systematic reviews and pharmacological studies on the antihyperglycemic effects of berberine, Rhizoma Coptidis extracts, and other Rhizoma Coptidis-containing agents.

3. Results

3.1. Overview of Systematic Reviews

Two systematic reviews on the antihyperglycemic effects of berberine were identified. In the first study authored by Dong et al. [13], a total of fourteen randomized controlled trials (RCTs) were included and the results of these studies were subjected to meta-analysis and subgroup analysis. In the later systematic review by Narenqimuge et al. [14], the results of the included ten RCTs were reported descriptively due to significant statistical heterogeneity across studies. The characteristics and results of these two systematic reviews were presented in Table 1.

Table 1.

A summary of findings from systematic reviews on the antihyperglycemic effects of berberine.

Outcomes Study
ID
Study
Year
Number
of RCTs
Number
of cases
Results Conclusion
FPG/PPG/HbA1c/FINS/TG/TC/LDL-C/HDL-C Dong et al. [13] 2012 4 271 Compared with lifestyle changes with or without placebo, berberine plus lifestyle changes showed significantly better hypoglycaemic and antidyslipidemic effects. Trials had poor methodological and reporting quality. The conclusions made were inconclusive and further research is needed.
FPG/HbA1c/TC/LDL-C Dong et al. [13] 2012 7 448 Compared with oral hypoglycaemics (metformin, glipizide, or rosiglitazone) berberine did not demonstrate significantly better hypoglycaemic effects but showed mild antidyslipidemic effects.
FPG/PPG/HbA1c/FINS/TG/TC/LDL-C/HDL-C Dong et al. [13] 2012 6 396 Compared with oral hypoglycaemic drugs, berberine combined with the same oral hypoglycaemics can better control blood sugar in the patients.

FBG/2hPBG/HbA1c/LDL-C/HDL-C/TG/TC/BMI Narenqimuge et al. [14] 2012 10 647 Berberine was effective in lowering FBG but not better than metformin, glipizide, or rosiglitazone. Berberine had no proven effects in decreasing PBG, HbAlc, or BMI and in regulating lipid metabolism. Trials were at high risk of bias. High-quality trials are needed.

Adverse events Dong et al. [13] 2012 14 1068 Three studies did not report AEs. Three reported no AEs. Three reported adverse events but did not indicate the group in which they occurred. Five reported AEs in the berberine group. No significant difference between the treatment and the control group.

Adverse events Narenqimuge et al. [14] 2012 7 435 Seven studies reported that AEs happened in the course of the treatment, mostly gastrointestinal reactions such as constipation and diarrhea. Of them 3 studies reported the number of cases of AEs. No significant difference between the treatment and the control group.

FPG: fasting blood glucose; PPG: postprandial plasma glucose; HbA1c: hemoglobin A1c; TG: triglyceride; TC: total cholesterol; LDL-C: low-density lipoprotein; HDL-C: high-density lipoprotein; FINS: fasting insulin; 2hPBG: 2-hour postprandial blood glucose; BMI: body mass index; AEs: adverse events.

Drawn upon the above research findings, the isoquinoline-type alkaloid berberine has beneficial effects for blood glucose control in the treatment of type 2 diabetic patients and exhibits efficacy comparable with that of conventional oral hypoglycaemics. No significant statistical difference in the incidence of adverse events was observed between groups. However, the evidence is inconclusive because clinical trials included in the two systematic reviews were of low methodological quality. Therefore, the antihyperglycemic effects of berberine warrant further examination and more rigorously controlled, methodologically sound, and scientifically designed RCTs need to be conducted.

3.2. Review of Pharmacological Research

A number of animal experiments investigating the antihyperglycemic effects of Rhizoma Coptidis, berberine, or herbal prescriptions in which Rhizoma Coptidis plays a dominant role were identified through electronic searches and careful screening. A summary of the experimental models used and the antidiabetic mechanism of berberine observed in these studies were presented in Table 2. From this table, we found the antidiabetic efficacy of berberine associated most closely with its ability to improve insulin sensitivity, influence insulin secretion, and regulate carbohydrate metabolism, and a majority of the pharmacological experiments focused on these aspects [1561]. Moreover, some additional bioactivities of berberine which may facilitate its antidiabetic effects were identified, such as its antioxidant, lipid regulatory, and anti-inflammatory functions as well as its renoprotective properties to prevent diabetes complications. These effects of berberine and the relevant mechanisms were demonstrated in Table 3.

Table 2.

Summary of berberine's effects on insulin and glucose metabolism and the mechanism of action [1561].

Experimental model Mechanism of action
T2DM Chinese hamsters Changed the expression of hepatic peroxisome proliferator-activated receptors and its target genes [15]
3T3-L1 cells Increased glucose uptake in fat cells and inhibited the differentiation of preadipocytes [16]
Sprague Dawley rats Reduced plasma FFA and triglyceride levels and inhibited the expression of liver TNF-α [17]
Sprague Dawley rats Increased HNF-4α expression [18]
Wistar rats Regulated the expression of endoplasmic reticulum chaperone ORP150 and reduced ER stress [19]
HepG2 cells Regulated AMPK activity to decrease its downstream gluconeogenesis protein expression [20]
Wistar rats Inhibited pancreatic β-cell apoptosis by inhibiting ASK1 protein expression [21]
Wistar rats Increased PI-3K p85 and GLUT4 protein expression in skeletal muscles of T2DM rats [22]
Insulin resistant rat models Inhibited TNF-α secretion and reduced serum free fatty acid level [23]
Wistar rats Increased mRNA expression of adiponectin gene and decreased IRI in T2DM rats [24]
T2DM Chinese hamsters Inhibited the expression of PEPCK, 6Pase, and PGC-1α by enhancing CYP7A1 and Gck expression induced by the upregulation of LXRα expression [25]
L6 myotubes Inhibited fatty acid uptake at least in part by reducing PPAR gamma and FAT/CD36 expression [26]
L6 rat skeletal muscle cells Induced InsR gene expression through a protein kinase C (PKC) dependent activation of its promoter. Inhibited PKC abolished BBR-caused InsR promoter activation and InsR mRNA transcription [27]
Nonalcoholic fatty liver
disease rat liver
Upregulated the mRNA and protein levels of IRS-2 [28]
3T3-L1 adipocytes Reversed free fatty acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ [29]
Cultured HepG2 cells Attenuated ER stress and improved insulin signal transduction [30]
Rat skeletal muscle cells Modulated key molecules in the insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells [31]
Insulin resistant rat models Stimulated AMPK activity [32]
T2DM hamsters Altered the transcriptional programs of the visceral white adipose tissue LXRs, PPARs, and SREBPs [33]
Diabetic hamsters Altered the transcriptional programs of hepatic SREBPs, LXRα, and PPARα [34]
Mouse primary hepatocyte Upregulated HNF4α expression to induce hepatic glucokinase activity [35]
Mouse primary hepatocyte Upregulated HNF6 mRNA expression and induced hepatic glucokinase activity [36]
HepG2 cells Increased hepatic glucose consumption [37]
Wistar rats Elevated IRS-1, IRS-2, and p85 mRNA expression in the peripheral tissues [38]
Sprague Dawley rats Increased the content of GLU4 mRNA in skeletal muscles, increased the content of GLUT4 protein in cells, and enhanced insulin activity in the peripheral tissues [39]
Kunming mice Inhibited gluconeogenesis and/or stimulated glycolysis [40]
Diabetic rat model Stimulated GLP-1 release [41]
Wistar rats Regulated INS and GH levels by enhancing SS levels through the hypothalamus-pituitary-pancreatic axis system [42]
HepG2 cells Increased InsR mRNA transcription and protein expression [43]
Alloxan-induced diabetic mice Upregulated the activity of Akt [44]
Wistar rats Stimulated GK activity and expression [45]
3T3-L1 adipocytes and L6 myocytes Inhibited PTP 1B activity and increased phosphorylation of IR, IRS1, and Akt in 3T3-L1 adipocytes [46]
Streptozotocin-induced
diabetic rats
Enhanced GLP-1-(7-36) amide secretion [47]
Mammalian cells Functioned as an agonist of the fatty acid receptor GPR40 [48]
T2DM rat models Lowered serum RBP4 levels and upregulated the expression of tissue GLUT4 protein [49]
Streptozotocin-induced
diabetic rats
Exhibited inhibitory effects on intestinal disaccharidases and β-glucuronidase [50]
L6 rat skeletal muscles Stimulated glucose uptake through the AMP-AMPK-p38 MAPK pathway [51]
3T3-L1 adipocytes Enhanced GLUT1 expression and stimulated the GLUT1-mediated glucose uptake by activating GLUT1 [52]
Alloxan-induced diabetic
C57BL/6 mice
Upregulated Akt activity via insulin signaling pathways [53]
Molecular model Inhibited H-PTP 1B [54]
Streptozotocin-induced
diabetic rats
Involved PKA-dependent pathways [55]
Normal animals
(dogs and rats)
Acutely inhibited α-glucosidase [56]
Molecular model Inhibited DPP IV [57]
L929 fibroblast cells Significantly activated GLUT1 transport [58]
Diabetic rats Directly inhibited gluconeogenesis in the liver [59]
Rat model Inhibition of glucose oxidation in mitochondria may contribute to increased AMP/ATP ratio and AMPK activation [60]
Caco-2 cell line Inhibited α-glucosidase activity and decreased glucose transport across the intestinal epithelium [61]

T2DM: type 2 diabetes mellitus; TNF: tumor necrosis factor; FFA: free fatty acid; HNF: hepatocyte nuclear factor; ER: endoplasmic reticulum; ORP: oxygen-regulated protein; AMPK: AMP-activated protein kinase; ASK: apoptosis signal-regulating kinase; mRNA: messenger RNA; IRI: insulin resistant index; PEPCK: phosphoenolpyruvate carboxylase kinase; PGC-1α: peroxisome proliferator-activated receptor-γ coactivator 1α; CYP7A1: cholesterol 7 α-hydroxylase; GCK: glucokinase; PI-3K: phosphatidylinositol 3-kinase; GLUT4: glucose transporter type 4; PPAR: peroxisome proliferator-activated receptor; FAT/CD36: fatty acid translocase; PKC: protein kinase C; BBR: berberine; IKKβ: inhibitor kappa B kinase β; LXRs: liver X receptors; SREBPs: sterol regulatory element binding proteins; IRS: insulin receptor substrates; GLP: glucagon-like peptide; INS: insulin; GH: growth hormone; SS: somatostatin; Akt: protein kinase B; PTP1B: protein tyrosine phosphatase 1B; IR: insulin resistance; GPR40: G protein-coupled receptor 40; RBP4: retinol-binding protein 4; H-PTP 1B: human protein tyrosine phosphatase 1B; DPP IV: dipeptidyl peptidase IV; AMP: adenosine monophosphate; ATP: adenosine triphosphate.

Table 3.

Summary of other effects of berberine and the mechanism of action [6276].

Effects Experimental model Mechanism of action
Antioxidative effects Type 2 diabetic rats Reduced oxidative stress [62]

Hypolipidemic effects Wistar rats Decreased blood FFA level and enhanced the activity of lipoprotein lipase [63]
Type 2 diabetic rats Increased PPARs and P-TEFb mRNA and protein expression in the adipose tissue. Restored SOD and LPL activity and normalized malondialdehyde, FFA, TNF-α, and adiponectin levels [64]
3T3-L1 adipocytes Increased glucose transport and consumption in 3T3-L1 adipocytes [65]
3T3-L1 adipocytes Modulated metabolism-related PPARs expression and differentiation-related P-TEFb expression in adipocytes [66]
3T3-L2 adipocytes Activated adenosine monophosphate, activated protein kinase [67]
Diabetic hyperlipidemic and normal rats Modulated metabolism-related PPAR alpha/delta/gamma protein expression in the liver [68]

Anti-inflammatory actions Type 2 diabetic rats Regulated serum levels of inflammatory factors such as CRP, IL-6, TNF-α, and adiponectin [69]

Effects on renal injury Glomerular mesangial cells Inhibited NF-κB activation and the expression of its downstream inflammatory factors to improve ECM accumulation and alleviate inflammatory injury in diabetic kidney [70]

Prevention of diabetes complications Type 2 diabetic rats Enhanced vascular smooth muscle activity [71]

Renal protective effects Rat glomerular mesangial cells Reduced the accumulation of extracellular matrix components including fibronectin and prevented the activation of the p38 MAPK signaling pathway [72]
Diabetic rats Inhibited glycosylation and exhibited antioxidative effects [73]
Diabetic C57BL/6 mice Deactivated the SphK-S1P signaling pathway [74]
Streptozotocin-induced diabetic rats Reduced oxidative stress and deactivated aldose reductase [75, 76]

SOD: superoxide dismutase; LPL: lipoprotein lipase; P-TEFb: positive transcription elongation factor b; CRP: C-reactive protein; IL-6: interleukin-6; NF-κb: nuclear transcription factor-κb; SphK: sphingosine kinase.

Findings from previous researches showed that the insulin-stimulated glucose uptake by target tissues such as adipocytes and skeletal muscles involved a series of signaling transduction cascades starting from insulin receptor (InsR) via insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI-3K) and leading to the translocation of glucose transporter (GLUT4) [77]. From this comprehensive review of the existing pharmacological research on the antihyperglycemic effects of Rhizoma Coptis and its major chemical ingredient berberine, the reviewers summarized a variety of possible mechanisms of action behind its antidiabetic properties, which include the promotion of insulin secretion and release, reparation of pancreatic islets β-cells, enhancement of insulin sensitivity, suppression of gluconeogenesis in the liver, promotion of glucose disposal in the periphery, and inhibition of aldose reductase [1561]. The mechanisms for Rhizoma Coptis and its component berberine's other bioactivities that may facilitate its antidiabetic functions include ameliorating oxidative stress accompanying diabetes, regulating plasma levels of adiponectin and other relevant inflammatory factors, increasing adipocytes glucose transportation and consumption, and modulating metabolism-related protein expression [6276].

In addition to the above findings, results from a few studies [7889] investigating the effects of Rhizoma Coptidis extracts, Rhizoma Coptidis-dominant couplet medicines, and Rhizoma Coptidis-containing Chinese patent drugs have showed them all to possess certain antihyperglycemic effects. Rhizoma Coptidis-dominant couplet medicines included Rhizoma Coptidis coupled with Panax Ginseng, Rhizoma Coptidis coupled with dried Rehmannia root, and a combination of Rhizoma Coptidis, Astragalus Mongholicus, and Solomonseal Rhizome. Rhizoma Coptidis-containing Chinese patent drug involved Jinlian Jiangtang capsules and Jinqi Jiangtang tablets. Their therapeutic properties, possible mechanisms, and other information were listed in Table 4.

Table 4.

Summary of the antihyperglycemic effects of Rhizoma Coptidis extracts, Rhizoma Coptidis-dominant couplet medicines, or Chinese patent drug and the relevant mechanisms [7889].

Drug Effects Experimental model Mechanism of actions
Rhizoma Coptidis decoction Antihyperglycemic
effects
Rat brain homogenate Inhibited pancreatic lipid peroxidation [78]
Reverse insulin resistance Rat model with metabolic syndrome Reversed insulin resistance, reduced visceral fat, and upregulated the expression of p-AMPK-A protein [79]

Water extracts of Rhizoma Coptidis Reverse insulin resistance 3T3-L1 preadipocytes Increased glucose uptake in preadipocytes [80]

Rhizoma Coptidis coupled with Panax Ginseng Enhance insulin sensitivity Type 2 diabetic rats Lowered TNF-α levels, prevented TNF-α from inhibiting the expression of GLUT4 in fat and muscle cells, improved autophosphorylation of insulin receptor, inhibited second messenger activation, and promoted lipolysis [81]
Reverse insulin resistance and regulate glucose and lipid metabolism Type 2 diabetic rats Reduced lipotoxicity [81]
Antihyperglycemic
effects
Type 2 diabetic rats Activated PPAR-γ, slowed the release of FFA, enhanced the sensitivity of skeletal muscles and the liver to insulin, reduced the exportation of glycogen, and promoted the uptake of glucose in skeletal muscles [81]
Reverse insulin resistance Type 2 diabetic rats Regulated FBG, INS, FFA, and TNF-α levels and improved insulin resistance [82]
Enhance insulin sensitivity Type 2 diabetic rats Regulated lipid metabolism and reversed lipotoxicity [83]

A combination of Rhizoma Coptidis, Astragalus Mongholicus, and Solomonseal Rhizome Vascular-protective Wistar rats Increased erythrocyte SOD activity and decreased serum MDA level, thereby reducing free radical damages in the hyperglycemic state [84]

Sanhuang compound (a mixture of Rhizoma Coptidis, Radix Astragali, and Radix Rehmanniae) Antihyperglycemic and hypolipidemic effects Type 2 diabetic rats Protected and repaired pancreas, enhanced insulin secretion and glycogenesis, and inhibited gluconeogenesis [85]

Rhizoma Coptidis coupled with dried Rehmannia root Reverse insulin resistance Type 2 diabetic rats Decreased the levels of inflammatory cytokine to improve insulin resistance and inhibited apoptosis of islet cells to protect islet β-cells [86]

Jinlian Jiangtang capsules Antihyperglycemic effects Kunming mice Promoted insulin release and glucose uptake and improved β-cell functioning [87]

Jinqi Jiangtang tablets Reverse insulin resistance and antihyperglycemic effects Wistar rats Inhibited resistin gene expression [88]
Antihyperglycemic effects 3T3-L1 cells and KK-Ay mice Activated the AMPK signaling pathway [89]

MDA: malondialdehyde.

4. Discussion

According to traditional beliefs, Chinese herbal remedy helps recover inner peace and tranquility in the human body with its multiple active constituents taking effects through various mechanisms and pathways. Therefore, the use of Chinese herbal medicines for diabetes treatment or for the prevention of diabetes complications might be generally considered good for the patients' general well-being, apart from their effectiveness and safety.

The existing evidence profile of the antihyperglycemic effects of Rhizoma Coptidis includes both textual records in ancient herbal classics and findings from animal experiments and systematic reviews of RCTs. Modern research uniformly focuses on berberine, whereas the pharmacological actions of other active ingredients of Rhizoma Coptidis, of single herb remedy, and of Rhizoma Coptidis-dominant couplet medicines and Rhizoma Coptidis-containing patent drug still remain to be investigated.

As was summarized in this review, the antihyperglycemic effects of Rhizoma Coptidis may rely upon drug actions on a variety of targets via multiple pathways. Many animal experiments [1576, 7889] have proposed the scientific rationale for Rhizoma Coptidis, Rhizoma Coptidis-containing agents, or its major component berberine's antihyperglycemic effects by identifying possible mechanisms of actions. The widespread use of Rhizoma Coptidis as a routine clinical treatment for diabetes is promising because there is abundant supply, the herb is relatively inexpensive, and it has a good safety profile [13, 14]. However, the results of both systematic reviews included in this study need to be interpreted with caution. As large-scale, rigorously controlled, and multicenter randomized controlled clinical studies are still lacking, the clinical efficacy and safety of Rhizoma Coptidis and berberine for antidiabetic use needs further investigation.

Furthermore, there were other issues to consider before Rhizoma Coptidis can be put into extensive clinical use. For instance, the most appropriate drug form and dosage, dose-effect relationship, and drug-drug interactions should be made clear through a series of pharmacological experiments and long-term clinical observations. Also, whether the antihyperglycemic effect is best exerted synergically in a prescription or independently as an active component remains to be investigated. Besides, the possible antidiabetic effects of the other chemical ingredients of Rhizoma Coptidis and the interactions among its various components, as well as the long-term health benefits of its use in diabetic patients, are all problems that need to be addressed in future research.

Acknowledgments

The funding support of the National Basic Research Program of China (973 Program no. 2009CB523003) and Tianjin Higher education institution “Innovative Team Training Program (NO. TD12-5032)” are gratefully acknowledged.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

References

  • 1.World Health Organization. Diabetes Programme: Diabetes Action Online. http://www.who.int/diabetes/action_online/basics/en/index.html.
  • 2.Gardner DG, Shoback D. Greenspan's Basic and Clinical Endocrinology. 9th edition. chapter 17. New York, NY, USA: Mc Graw-Hill Medical; 2011. [Google Scholar]
  • 3.Kumar V, Fausto N, Abbas AK, Cotran RS, Robbins SL. Robbins and Cotran Pathologic Basis of Disease. 7th edition. Philadelphia, Pa, USA: Saunders; 2005. [Google Scholar]
  • 4.World Health Organization. Diabetes fact sheets. http://www.who.int/mediacentre/factsheets/fs312/en/index.html.
  • 5.Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Vol. 1. Beijing, China: Chinese Medical Science and Technology Press; 2010. [Google Scholar]
  • 6.Liu JL, Meng XL, Liu YS. Discussion on the ancient use of coptis chinensis for treating diabetes. Sichuan Journal of Traditional Chinese Medicine. 2010;28(4):41–43. [Google Scholar]
  • 7.Editorial Board of Chinese Materia Medica organized by the State Administration of Traditional Chinese Medicine. Chinese Materia Medica. Shanghai, China: Shanghai Science and Technology Publishing House; 1996. [Google Scholar]
  • 8.Fang YZ. Practical Chinese Internal Medicine. Shanghai, China: Shanghai Science and Technology Publishing House; 1982. [Google Scholar]
  • 9.Tang S, Zhang Y, Tu X, et al. A literature review on the current reserch of the mechanism of berberine for lowering blood sugar in type 2 diabetes patients. Journal of Chinese Medicine. 2012;27(7):850–851. [Google Scholar]
  • 10.Lan J, Yang SL, Deng YQ, et al. Overview of research on coptis chinensis. Chinese Herbal Medicines. 2001;32(12):p. 1139. [Google Scholar]
  • 11.Tian ZY, Li ZG. A review of new progress in the research of coptis chinensis. Lishenzhen Medicine and Materia Medica Research. 2004;15(10):p. 704. [Google Scholar]
  • 12.Yuan Z. Application and Thinking of Hypoglycemic Effect of Rhizoma Coptidis in Diabetes Treatment. Beijing, China: Beijing University of Chinese Medicine; 2011. [Google Scholar]
  • 13.Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine. 2012;2012:12 pages. doi: 10.1155/2012/591654.591654 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Narenqimuge N, Zhao TY, He M, Tian C. Effectiveness and safety of berberine in the treatment of type 2 diabetes: a systematic review. Chinese Journal of Evidence-Based Medicine. 2012;12(1):81–91. [Google Scholar]
  • 15.Liu XH, Li GS, Huang L, Zhu H, Liu YL, Ma CM. Effects of berberine on expression of hepatic peroxisome proliferator-activated receptors and its target genes in type 2 diabetic chinese hamsters. Journal of Clinical Rehabilitative Tissue Engineering Research. 2011;15(24):4409–4414. [Google Scholar]
  • 16.Wang SH, Wang WJ, Wang XF, Chen W. Effect of Astragalus polysaccharides and berberine on carbohydrate metabolism and cell differentiation in 3T3-L1 adipocytes. Chinese Journal of Integrative Medicine. 2004;24(10):926–928. [PubMed] [Google Scholar]
  • 17.Gao ZQ, Leng SH, Lu FE, Xie MJ, Xu LJ, Wang KF. Effect of berberine on fructose-induced insulin resistance and expression of tumor necrosis factor-alpha in liver of rats. Chinese Pharmacological Bulletin. 2008;24(11):1479–1482. [Google Scholar]
  • 18.Gao ZQ, Lu FE, Leng SH, et al. Effects of berberine on the expression of hepatocyte nuclear factor-4α in rats with fructose-induced insulin resistance. World Chinese Journal of Digestology. 2008;16(15):1681–1684. [Google Scholar]
  • 19.Zhao Y, Lu FE, Wu S, et al. Endocrine and Metabolic Diseases of Integrative Medicine—Clinical and Basic. 2010. Effect of berberine on expression of ORP150 in rats with insulin resistance induced by high fructose and fat diet; pp. 301–304. [Google Scholar]
  • 20.Kuan X, Lu FE, Yi P, et al. Effects of berberine on glucose metabolism in insulin-resistant HepG2 cells. Proceedings of the Diabetes Forum of the 5th National Conference on Integrative Medicine for Endocrinology and Metabolism Diseases; 2012; pp. 137–143. [Google Scholar]
  • 21.Wu S, Lu FE, Dong H, et al. Effect of berberine on the pancreatic ß cell apoptosis in rats with insulin resistance. Chinese Journal of Integrative Medicine. 2011;31(10):1383–1388. [PubMed] [Google Scholar]
  • 22.Chen G, Lu FE, Wang ZS, et al. Correlation between the amelioration of insulin resistance and protein expression of PI-3K and GLUT4 in type 2 diabetic rats treated with berberine. Chinese Pharmacological Bulletin. 2008;24(8):1007–1010. [Google Scholar]
  • 23.Lu H, Ye WC, Ding XP. Effect of berberine on insulin resistance in rat. Journal of Liaoning College of Traditional Chinese Medicine. 2002;4(4):259–260. [Google Scholar]
  • 24.Ren FY, Wang GY, Cui RJ. Effect of berberine on gene expression of adiponectin in type 2 diabetic mellitus rats. Medical Recapitulate. 2009;15(14):2210–2212. [Google Scholar]
  • 25.Li GS, Liu XH, Huang L, et al. Influence of berberine on expression of hepatic X receptors and their target genes in liver of Chinese hamsters with type 2 diabetes meilitus. Modern Journal of Integrated Traditional Chinese and Western Medicine. 2011;20(17):2099–2103. [Google Scholar]
  • 26.Chen Y, Li Y, Wang Y, Wen Y, Sun C. Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor γ and fatty acid transferase expressions. Metabolism: Clinical and Experimental. 2009;58(12):1694–1702. doi: 10.1016/j.metabol.2009.06.009. [DOI] [PubMed] [Google Scholar]
  • 27.Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism: Clinical and Experimental. 2009;58(1):109–119. doi: 10.1016/j.metabol.2008.08.013. [DOI] [PubMed] [Google Scholar]
  • 28.Xing LJ, Zhang L, Liu T, Hua YQ, Zheng PY, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. European Journal of Pharmacology. 2011;668(3):467–471. doi: 10.1016/j.ejphar.2011.07.036. [DOI] [PubMed] [Google Scholar]
  • 29.Yi P, Lu FE, Xu LJ, Chen G, Dong H, Wang KF. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ . World Journal of Gastroenterology. 2008;14(6):876–883. doi: 10.3748/wjg.14.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Wang ZS, Lu FE, Xu LJ, Dong H. Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells. Acta Pharmacologica Sinica. 2010;31(5):578–584. doi: 10.1038/aps.2010.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Liu LZ, Cheung SCK, Lan LL, et al. Berberine modulates insulin signaling transduction in insulin-resistant cells. Molecular and Cellular Endocrinology. 2010;317(1-2):148–153. doi: 10.1016/j.mce.2009.12.027. [DOI] [PubMed] [Google Scholar]
  • 32.Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55(8):2256–2264. doi: 10.2337/db06-0006. [DOI] [PubMed] [Google Scholar]
  • 33.Li GS, Liu XH, Zhu H, et al. Berberine-improved visceral white adipose tissue insulin resistance associated with altered sterol regulatory element-binding proteins, liver X receptors, and peroxisome proliferator-activated receptors transcriptional programs in diabetic hamsters. Biological and Pharmaceutical Bulletin. 2011;34(5):644–654. doi: 10.1248/bpb.34.644. [DOI] [PubMed] [Google Scholar]
  • 34.Liu X, Li G, Zhu H, et al. Beneficial effect of berberine on hepatic insulin resistance in diabetic hamsters possibly involves in SREBPs, LXRα and PPARα transcriptional programs. Endocrine Journal. 2010;57(10):881–893. doi: 10.1507/endocrj.k10e-043. [DOI] [PubMed] [Google Scholar]
  • 35.Yan ZQ, Leng SH, Lu FE, Lu XH, Dong H, Gao ZQ. Effects of berberine on expression of hepatocyte nuclear factor 4α and glucokinase activity in mouse primary hepatocytes. China Journal of Chinese Materia Medica. 2008;33(18):2105–2109. [PubMed] [Google Scholar]
  • 36.Yan ZQ, Leng SH, Lu FE, Lu XH, Dong H, Gao ZQ. Effects of berberine on expression of hepatocyte nuclear factor 6 and glucokinase activity in mouse primary hepatocytes. World Chinese Journal of Digestology. 2007;15(36):3842–3846. [PubMed] [Google Scholar]
  • 37.Yin J, HU RM, Tang JF, et al. Glucose-lowering effect of berberine in vitro. Journal of Shanghai Second Medical University. 2001;21(5):425–427. [Google Scholar]
  • 38.Shu S, Liu XM, Song LN, et al. Effects of berberine on the gene expression of IRS-1/-2 and p85 in type 2 diabetes mellitus rats. Zhejiang Journal of Traditional Chinese Medicine. 2009;44(4):254–257. [Google Scholar]
  • 39.Duan WL, Li YM, Yang XF, et al. Effects of berberine on glucose transporter IV in skeletal muscle of type 2 diabetic rats. Chinese Journal of Integrative Medicine. 1999;19:82–83. [Google Scholar]
  • 40.Chen QM, Xie MZ. Effects of berberine on blood glucose regulation of normal mice. Acta Pharmaceutica Sinica. 1987;22(3):161–165. [PubMed] [Google Scholar]
  • 41.Lv QJ, Cao SQ, Pu QH. Effect of berberine on secretion of GLP-1 in diabetic rats. Neijiang Science and Technology. 2010;31(12):p. 64. [Google Scholar]
  • 42.Hua WG, Song JM, Liao H, et al. Effect of Huang Lian Su on nerve conduction velocity and hormone level to diabetic neuropathy in rats. Labeled Immunoassays and Clinical Medicine. 2001;8(4):212–214. [Google Scholar]
  • 43.Zhang H, Kong WJ, Jiang JD. Berberine raised insulin receptor expression through protein kinase C-dependent pathway. Proceedings of the Chemistry of Traditional Chinese Medicine Session of the 2008 Symposium of the Chinese Assosciation of Traditional Chinese Meidicine; 2008; pp. 191–195. [Google Scholar]
  • 44.Xie X, Li WY, Huang HQ. Berberine reduced blood sugar in alloxan-induced diabetic mice through activation of Akt signaling pathway. Proceedings of the 11th Central and South China Symposium of Experimental Animal Science and Technology; 2011; pp. 540–555. [Google Scholar]
  • 45.Rong TZ, Lu FE, Chen G, Xu LJ, Wang KF, Zou X. Effect of berberine on glucokinase and its related glucose metabolism in rats with insulin-secretion deficiency. Chinese Traditional and Herbal Drugs. 2007;38(5):725–728. [Google Scholar]
  • 46.Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics insulin action. Biochemical and Biophysical Research Communications. 2010;397(3):543–547. doi: 10.1016/j.bbrc.2010.05.153. [DOI] [PubMed] [Google Scholar]
  • 47.Lu SS, Yu YL, Zhu HJ, et al. Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats. Journal of Endocrinology. 2009;200(2):159–165. doi: 10.1677/JOE-08-0419. [DOI] [PubMed] [Google Scholar]
  • 48.Rayasam GV, Tulasi VK, Sundaram S, et al. Identification of berberine as a novel agonist of fatty acid receptor GPR40. Phytotherapy Research. 2010;24(8):1260–1263. doi: 10.1002/ptr.3165. [DOI] [PubMed] [Google Scholar]
  • 49.Zhang W, Xu YC, Guo FJ, Meng Y, Li ML. Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus. Chinese Medical Journal. 2008;121(21):2124–2128. [PubMed] [Google Scholar]
  • 50.Liu L, Deng Y, Yu S, Lu S, Xie L, Liu X. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats. Pharmazie. 2008;63(5):384–388. [PubMed] [Google Scholar]
  • 51.Cheng Z, Pang T, Gu M, et al. Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK. Biochimica et Biophysica Acta: General Subjects. 2006;1760(11):1682–1689. doi: 10.1016/j.bbagen.2006.09.007. [DOI] [PubMed] [Google Scholar]
  • 52.Kim SH, Shin EJ, Kim ED, Bayaraa T, Frost SC, Hyun CK. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biological and Pharmaceutical Bulletin. 2007;30(11):2120–2125. doi: 10.1248/bpb.30.2120. [DOI] [PubMed] [Google Scholar]
  • 53.Xie X, Li W, Lan T, et al. Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway. Endocrine Journal. 2011;58(9):761–768. doi: 10.1507/endocrj.k11e-024. [DOI] [PubMed] [Google Scholar]
  • 54.Bustanji Y, Taha MO, Yousef AM, Al-Bakri AG. Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental validation. Journal of Enzyme Inhibition and Medicinal Chemistry. 2006;21(2):163–171. doi: 10.1080/14756360500533026. [DOI] [PubMed] [Google Scholar]
  • 55.Liu L, Yu YL, Yang JS, et al. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2010;381(4):371–381. doi: 10.1007/s00210-010-0502-0. [DOI] [PubMed] [Google Scholar]
  • 56.Li ZQ, Zuo DY, Qie XD, et al. Berberine acutely inhibits the digestion of maltose in the intestine. Journal of Ethnopharmacology. 2012;142(2):474–480. doi: 10.1016/j.jep.2012.05.022. [DOI] [PubMed] [Google Scholar]
  • 57.Al-Masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. Journal of Enzyme Inhibition and Medicinal Chemistry. 2009;24(5):1061–1066. doi: 10.1080/14756360802610761. [DOI] [PubMed] [Google Scholar]
  • 58.Cok A, Plaisier C, Salie MJ, Oram DS, Chenge J, Louters LL. Berberine acutely activates the glucose transport activity of GLUT1. Biochimie. 2011;93(7):1187–1192. doi: 10.1016/j.biochi.2011.04.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Xia X, Yan J, Shen Y, et al. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS ONE. 2011;6(2) doi: 10.1371/journal.pone.0016556.e16556 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. American Journal of Physiology—Endocrinology and Metabolism. 2008;294(1):E148–E156. doi: 10.1152/ajpendo.00211.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Pan GY, Huang ZJ, Wang GJ, et al. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Medica. 2003;69(7):632–636. doi: 10.1055/s-2003-41121. [DOI] [PubMed] [Google Scholar]
  • 62.Wang J, Yuan ZM, Kong HW, et al. Exploring the mechanism of rhizoma coptidis in treating type II diabetes mellitus based on metabolomics by gas chromatography-mass spectrometry. Chinese Journal of Chromatography. 2012;30(1):8–13. doi: 10.3724/sp.j.1123.2011.08039. [DOI] [PubMed] [Google Scholar]
  • 63.He MK, Lu FE, Wang KF, et al. Effect and mechanisms of berberine on hyperlipidemic and insulin resistant rat. Chinese Journal of Hospital Pharmacy. 2004;24(7):389–391. [Google Scholar]
  • 64.Zhou JY, Zhou SW. Effects of berberine the expression of PPARs/PTEFb in adipose tissue of type 2 diabetic rats. Proceedings of the Symposium on Medicinal Chemistry and Analysis of the Active Components of Chinese Herbal Medicine; 2008; pp. 188–199. [Google Scholar]
  • 65.Zhou LB, Yang Y, Ta JF, et al. Effects of berberine on glucose metabolism in adipocyte. Journal of Shanghai Second Medical University. 2002;22(5):412–414. [Google Scholar]
  • 66.Zhou J, Zhou S. Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes. European Journal of Pharmacology. 2010;649(1–3):390–397. doi: 10.1016/j.ejphar.2010.09.030. [DOI] [PubMed] [Google Scholar]
  • 67.Zhou L, Yang Y, Wang X, et al. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism: Clinical and Experimental. 2007;56(3):405–412. doi: 10.1016/j.metabol.2006.10.025. [DOI] [PubMed] [Google Scholar]
  • 68.Zhou JY, Zhou SW, Zhang KB, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biological and Pharmaceutical Bulletin. 2008;31(6):1169–1176. doi: 10.1248/bpb.31.1169. [DOI] [PubMed] [Google Scholar]
  • 69.Dai JF. Research on the therapeutic effect and mechanism of Berberine in Rats with Type 2 Diabetes mellitus [M.S. thesis] Luzhou Medical College; 2009. [Google Scholar]
  • 70.Qin J. Effects of berberine on NF-κB activation and its downstream inflammatory factors expression in LPS—induced rat mesangial cells [M.S. thesis] Sun Yat-sen University; 2010. [Google Scholar]
  • 71.Liu XY. Change of vascular smooth muscle reactivity in T2DM rats and intervention of Berberine [M.S. thesis] Luzhou Medical College; 2012. [Google Scholar]
  • 72.Qin ZY, Liu WH, Huang HQ. Effects of berberine on fibronectin and p38MAPK signal pathway in rat glomerular mesangial cells cultured under high glucose condition. Chinese Pharmacological Bulletin. 2009;25(9):1201–1205. [Google Scholar]
  • 73.Wu D, Wen W, Qi CL, et al. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine. 2012;19(8-9):712–718. doi: 10.1016/j.phymed.2012.03.003. [DOI] [PubMed] [Google Scholar]
  • 74.Lan T, Shen X, Liu P, et al. Berberine ameliorates renal injury in diabetic C57BL/6 mice: involvement of suppression of SphK-S1P signaling pathway. Archives of Biochemistry and Biophysics. 2010;502(2):112–120. doi: 10.1016/j.abb.2010.07.012. [DOI] [PubMed] [Google Scholar]
  • 75.Liu WH, Hei ZQ, Nie H, et al. Berberine ameliorates renal injury in streptopzotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chinese Medical Journal. 2008;121(8):706–712. [PubMed] [Google Scholar]
  • 76.Liu W, Liu P, Tao S, et al. Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Archives of Biochemistry and Biophysics. 2008;475(2):128–134. doi: 10.1016/j.abb.2008.04.022. [DOI] [PubMed] [Google Scholar]
  • 77.Wojtaszewski JFP, Hansen BF, Kiens B, Richter EA. Insulin signaling in human skeletal muscle: time course and effect of exercise. Diabetes. 1997;46(11):1775–1781. doi: 10.2337/diab.46.11.1775. [DOI] [PubMed] [Google Scholar]
  • 78.Song LC, Chen KZ, Zhu JY. The effect of Coptis chinensis on lipid peroxidation and antioxidases activity in rats. Chinese Journal of Integrative Medicine. 1992;12(7):421–423. [PubMed] [Google Scholar]
  • 79.Qiao LL, Huang F, Yan XG, et al. Effects of berberine on AMPK expression in skeletal muscle of metabolic syndrome rat. China Journal of Traditional Chinese Medicine and Pharmacy. 2010;25(1):145–148. [Google Scholar]
  • 80.Li JC, Meng XL, Fan XJ, Lai X, Zhang Y, Zeng Y. Pharmacodyamic material basis of Rhizoma Coptidis on insulin resistance. China Journal of Chinese Materia Medica. 2010;35(14):1855–1858. doi: 10.4268/cjcmm20101419. [DOI] [PubMed] [Google Scholar]
  • 81.Jiang M. Insulin resistance mechanism of huanglian-renshen pair in type 2 diabetes mellitus [Ph.D. thesis] Beijing University of Traditional Chinese Medicine; 2006. [Google Scholar]
  • 82.Jiang M, Wang SD, Huang YY, et al. An experimental study on paired medicines of coptidis and ginseng for the treatment of type 2 diabetic insulin-resistance. New Journal of Traditional Chinese Medicine. 2006;38(5):89–91. [Google Scholar]
  • 83.Li LF, Wang SD, Jiang M. Effect of ginseng and coptis on glucosemetabolism and lipometabolism in type II diabetes mellitus in rats. Chinese Journal of Basic Medicine in Traditional Chinese Medicine. 2006;12(9):707–708. [Google Scholar]
  • 84.Song YG. Experimental research of combination of astragalus root, siberian solomonseal rhizome and coptis root on lowering blood sugar [M.S. thesis] Shandong University of Traditional Chinese Medicine; 2002. [Google Scholar]
  • 85.Xu NN, Zhu BC, Wang Z, et al. Effect of san huang compound on metabolism of glucose and lipid in type II diabetes mellitus rats. Lishenzhen Medicine and Materia Medica Research. 2008;19(11):2677–2679. [Google Scholar]
  • 86.Zhao J. Comparative study on therapeutic effect and its mechanism of coptidis rhizome, rehmannia dride rhizome and their compatibility on type 2 diabetic mellitus rats [M.S. thesis] Huazhong University of Science and Technology; 2011. [Google Scholar]
  • 87.Li HF, Zhu YZ, Ye Q, et al. Experimental study of the hypoglycemic effect of Jinlian Jiangtang capsule. Chinese Traditional Patent Medicine. 2008;30(6):913–914. [Google Scholar]
  • 88.Tang H, Zhu L, Wang LH. Effect of Jinqi Jiangtang tablets on serum resistin in insulin resistance rats. Chinese Journal of Clinical Medicine Research. 2008;192:1–2. [Google Scholar]
  • 89.Qian Q, Liu X, He W, et al. TG accumulation inhibitory effects of Jinqi formula by AMPK signaling pathway. Journal of Ethnopharmacology. 2012;143(1):41–48. doi: 10.1016/j.jep.2012.05.052. [DOI] [PubMed] [Google Scholar]

Articles from BioMed Research International are provided here courtesy of Wiley

RESOURCES