BioMed Research International

BioMed Research International / 2014 / Article

Review Article | Open Access

Volume 2014 |Article ID 798093 | 10 pages | https://doi.org/10.1155/2014/798093

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

Academic Editor: Mila Emerald
Received10 Jan 2014
Revised10 Mar 2014
Accepted18 Mar 2014
Published10 Apr 2014

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.


OutcomesStudy
ID
Study
Year
Number
of RCTs
Number
of cases
ResultsConclusion

FPG/PPG/HbA1c/FINS/TG/TC/LDL-C/HDL-CDong et al. [13]20124271Compared 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-CDong et al. [13]20127448Compared 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-CDong et al. [13]20126396Compared 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]201210647Berberine 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 eventsDong et al. [13]2012141068Three 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 eventsNarenqimuge et al. [14]20127435Seven 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.


Experimental model Mechanism of action

T2DM Chinese hamstersChanged the expression of hepatic peroxisome proliferator-activated receptors and its target genes [15]
3T3-L1 cellsIncreased glucose uptake in fat cells and inhibited the differentiation of preadipocytes [16]
Sprague Dawley ratsReduced plasma FFA and triglyceride levels and inhibited the expression of liver TNF-α [17]
Sprague Dawley ratsIncreased HNF-4α expression [18]
Wistar ratsRegulated the expression of endoplasmic reticulum chaperone ORP150 and reduced ER stress [19]
HepG2 cellsRegulated AMPK activity to decrease its downstream gluconeogenesis protein expression [20]
Wistar ratsInhibited pancreatic β-cell apoptosis by inhibiting ASK1 protein expression [21]
Wistar ratsIncreased PI-3K p85 and GLUT4 protein expression in skeletal muscles of T2DM rats [22]
Insulin resistant rat modelsInhibited TNF-α secretion and reduced serum free fatty acid level [23]
Wistar ratsIncreased mRNA expression of adiponectin gene and decreased IRI in T2DM rats [24]
T2DM Chinese hamstersInhibited 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 modelsStimulated AMPK activity [32]
T2DM hamsters Altered the transcriptional programs of the visceral white adipose tissue LXRs, PPARs, and SREBPs [33]
Diabetic hamstersAltered the transcriptional programs of hepatic SREBPs, LXRα, and PPARα [34]
Mouse primary hepatocyteUpregulated HNF4α expression to induce hepatic glucokinase activity [35]
Mouse primary hepatocyteUpregulated HNF6 mRNA expression and induced hepatic glucokinase activity [36]
HepG2 cellsIncreased hepatic glucose consumption [37]
Wistar ratsElevated IRS-1, IRS-2, and p85 mRNA expression in the peripheral tissues [38]
Sprague Dawley ratsIncreased 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 miceInhibited gluconeogenesis and/or stimulated glycolysis [40]
Diabetic rat modelStimulated GLP-1 release [41]
Wistar ratsRegulated INS and GH levels by enhancing SS levels through the hypothalamus-pituitary-pancreatic axis system [42]
HepG2 cellsIncreased InsR mRNA transcription and protein expression [43]
Alloxan-induced diabetic miceUpregulated the activity of Akt [44]
Wistar ratsStimulated GK activity and expression [45]
3T3-L1 adipocytes and L6 myocytesInhibited 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 musclesStimulated glucose uptake through the AMP-AMPK-p38 MAPK pathway [51]
3T3-L1 adipocytesEnhanced 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 modelInhibited 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 ratsDirectly 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 lineInhibited 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 -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.

EffectsExperimental model Mechanism of action

Antioxidative effects Type 2 diabetic ratsReduced oxidative stress [62]

Hypolipidemic effectsWistar ratsDecreased blood FFA level and enhanced the activity of lipoprotein lipase [63]
Type 2 diabetic ratsIncreased 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 adipocytesIncreased 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 adipocytesActivated adenosine monophosphate, activated protein kinase [67]
Diabetic hyperlipidemic and normal ratsModulated metabolism-related PPAR alpha/delta/gamma protein expression in the liver [68]

Anti-inflammatory actionsType 2 diabetic ratsRegulated serum levels of inflammatory factors such as CRP, IL-6, TNF-α, and adiponectin [69]

Effects on renal injuryGlomerular mesangial cellsInhibited 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 complicationsType 2 diabetic ratsEnhanced vascular smooth muscle activity [71]

Renal protective effectsRat glomerular mesangial cellsReduced the accumulation of extracellular matrix components including fibronectin and prevented the activation of the p38 MAPK signaling pathway [72]
Diabetic ratsInhibited glycosylation and exhibited antioxidative effects [73]
Diabetic C57BL/6 miceDeactivated the SphK-S1P signaling pathway [74]
Streptozotocin-induced diabetic ratsReduced 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 -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.


DrugEffectsExperimental modelMechanism of actions

Rhizoma Coptidis decoctionAntihyperglycemic
effects
Rat brain homogenateInhibited pancreatic lipid peroxidation [78]
Reverse insulin resistanceRat model with metabolic syndromeReversed insulin resistance, reduced visceral fat, and upregulated the expression of p-AMPK-A protein [79]

Water extracts of Rhizoma CoptidisReverse insulin resistance3T3-L1 preadipocytesIncreased glucose uptake in preadipocytes [80]

Rhizoma Coptidis coupled with Panax GinsengEnhance insulin sensitivityType 2 diabetic ratsLowered 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 ratsReduced lipotoxicity [81]
Antihyperglycemic
effects
Type 2 diabetic ratsActivated 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 resistanceType 2 diabetic ratsRegulated FBG, INS, FFA, and TNF-α levels and improved insulin resistance [82]
Enhance insulin sensitivityType 2 diabetic ratsRegulated lipid metabolism and reversed lipotoxicity [83]

A combination of Rhizoma Coptidis, Astragalus Mongholicus, and Solomonseal RhizomeVascular-protectiveWistar ratsIncreased 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 effectsType 2 diabetic ratsProtected and repaired pancreas, enhanced insulin secretion and glycogenesis, and inhibited gluconeogenesis [85]

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

Jinlian Jiangtang capsulesAntihyperglycemic effectsKunming micePromoted insulin release and glucose uptake and improved β-cell functioning [87]

Jinqi Jiangtang tabletsReverse insulin resistance and antihyperglycemic effects Wistar ratsInhibited resistin gene expression [88]
Antihyperglycemic effects3T3-L1 cells and KK-Ay miceActivated 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.

Conflict of Interests

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

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.

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