Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension

Lan, Jiarong; Zhao, Yanyun; Fang, Dong; Yan, Ziyou; Zheng, Wei; Fan, Jinping; Sun, Guoli

doi:10.1016/j.jep.2014.09.049

Cited by 354 publications

(243 citation statements)

References 10 publications

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“…These results suggest that berberine exerts its anti-diabetic effect in ZDF rats by moderating the diabetic metabolism. These results are similar to those obtained in previous studies [7,16,17,18,19]. The administered dosage (300mg/kg) of berberine was determined according to the equation used for the adult maximal dosage in the clinic [7].…”

Section: Discussionsupporting

confidence: 84%

Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

Chen

Bao

et al. 2016

PLoS ONE

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BackgroundBerberine is used to treat diabetes and dyslipidemia. However, the effect of berberine on specific diabetes treatment targets is unknown. In the current study, we investigated the effect of berberine on the random plasma glucose, glycated hemoglobin (HbA1C), AST, ALT, BUN and CREA levels of Zucker diabetic fatty (ZDF) rats, and we identified and verified the importance of potential therapeutic target genes to provide molecular information for further investigation of the mechanisms underlying the anti-diabetic effects of berberine.MethodsZDF rats were randomly divided into control (Con), diabetic (DM) and berberine-treated (300 mg⋅kg−1, BBR) groups. After the ZDF rats were treated with BBR for 12 weeks, its effect on the random plasma glucose and HbA1C levels was evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), CREA and OGTT were measured from blood, respectively. The levels of gene expression in liver samples were analyzed using an Agilent rat gene expression 4x44K microarray. The differentially expressed genes (DEGs) were screened as those with log2 (Con vs DM) ≥ 1 and log2 (BBR vs DM) ≥ 1 expression levels, which were the genes with up-regulated expression, and those with log2 (Con vs DM) ≤ -1 and log2 (BBR vs DM) ≤ -1 expression levels, which were the genes with down-regulated expression; the changes in gene expression were considered significant at P<0.05. The functions of the DEGs were determined using gene ontology (GO) and pathway analysis. Furthermore, a protein-protein interaction (PPI) network was constructed using STRING and Cytoscape software. The expression levels of the key node genes in the livers of the ZDF rats were also analyzed using qRT-PCR.ResultsWe found that 12 weeks of berberine treatment significantly decreased the random plasma glucose, HbA1C levels and improved glucose tolerance. There was a tendency for berberine to reduce AST, ALT, BUN except increase CREA levels. In the livers of the BBR group, we found 154 DEGs, including 91 genes with up-regulated expression and 63 genes with down-regulated expression. In addition, GO enrichment analysis showed significant enrichment of the DEGs in the following categories: metabolic process, localization, cellular process, biological regulation and response to stimulus process. After the gene screening, KEGG pathway analysis showed that the target genes are involved in multiple pathways, including the lysine degradation, glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and pyruvate metabolism pathways. By combining the results of PPI network and KEGG pathway analyses, we identified seven key node genes. The qRT-PCR results confirmed that the expression of the RHOA, MAPK4 and DLAT genes was significantly down-regulated compared with the levels in DM group, whereas the expression of the SgK494, DOT1L, SETD2 and ME3 genes was significantly up-regulated in the BBR group.ConclusionBerberine can significantly improve glucose metabolism and has a protective effects of li...

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Section: Discussionsupporting

confidence: 84%

Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

Chen

Bao

et al. 2016

PLoS ONE

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“…Intriguingly, numerous clinical trials [6][7][8][9][10] . BBR has been found to prevent ischemia-induced ventricular tachyarrhythmias, enhance the force of cardiac contractions, and decrease peripheral vascular resistance and blood pressure [11][12][13][14] . Recently, we have also demonstrated that Notch1 signaling plays a key role in BBR's cardioprotective action [15] .…”

Section: Introductionmentioning

confidence: 99%

Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress

et al. 2016

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Aim: Berberine (BBR), an isoquinoline-derived alkaloid isolated from Rhizoma coptidis, exerts cardioprotective effects. Because endoplasmic reticulum (ER) stress plays a pivotal role in myocardial ischemia/reperfusion (MI/R)-induced apoptosis, it was interesting to examine whether the protective effects of BBR resulted from modulating ER stress levels during MI/R injury, and to define the signaling mechanisms in this process. Methods: Male rats were treated with BBR (200 mg·kg -1 ·d -1 , ig) for 2 weeks, and then subjected to MI/R surgery. Cardiac dimensions and function were assessed using echocardiography. Myocardial infarct size and apoptosis was examined. Total serum LDH levels and CK activities, superoxide production, MDA levels and the antioxidant SOD activities in heart tissue were determined. An in vitro study was performed on cultured rat embryonic myocardium-derived cells H9C2 exposed to simulated ischemia/reperfusion (SIR). The expression of apoptotic, ER stress-related and signaling proteins were assessed using Western blot analyses. Results: Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage. Furthermore, pretreatment with BBR suppressed MI/R-induced ER stress, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues. Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues, and co-treatment with AG490, a specific JAK2/STAT3 inhibitor, blocked not only the protective effects of BBR, but also the inhibition of BBR on MI/R-induced ER stress. In H9C2 cells, treatment with BBR (50 μmol/L) markedly reduced SIR-induced cell apoptosis, oxidative stress and ER stress, which were abolished by transfection with JAK2 siRNA. Conclusion: BBR ameliorates MI/R injury in rats by activating the AK2/STAT3 signaling pathway and attenuating ER stress-induced apoptosis.Keywords: berberine; myocardial ischemia/reperfusion injury; apoptosis; ER stress; oxidative stress; JAK2/STAT3; AG490 Acta Pharmacologica Sinica (2016) 37: 354-367; doi: 10.1038/aps.2015 published online 25 Jan 2016 Original Article # These authors contributed equally to this work. * To whom correspondence should be addressed. E-mail yunwangww@163.com (Yun WANG);shiqiangyu210@126.com (Shi-qiang YU) Received 2015-08-26 Accepted 2015-11-20 IntroductionIschemic heart disease remains the leading cause of mortality and disability worldwide. Although timely reperfusion therapy is the primary treatment, reperfusion itself results in major cardiac damage, commonly referred to as myocardial ischemia/reperfusion (MI/R) injury [1,2] . The endoplasmic reticulum (ER) is a multifunctional organelle in eukaryotic cells, which participates in the biosynthesis and folding of proteins. MI/R injury is known to result in the accumulation of unfolded proteins in the ER, which causes a severe unfolded protein response (UPR). Persistent UPR eventually ...

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“…[1][2][3] Such properties have been associated to the presence of benzylisoquinoline alkaloids (BIA's), which are distributed through the entire plant 4 . The main Argemone alkaloids are berberine (Bn), chelerythrine (C) and sanguinarine (S), which belong to the protoberberine (Bn) and benzophenanthridine (C and S) types.…”

Section: Introductionmentioning

confidence: 99%

“…The main Argemone alkaloids are berberine (Bn), chelerythrine (C) and sanguinarine (S), which belong to the protoberberine (Bn) and benzophenanthridine (C and S) types. 4 Bn supplements are employed as insulin sensitizers in treatments for diabetes type 2 patients, as well as for dyslipidemia. Furthermore, it has been included in the formulation of environmentally friendly agrochemicals.…”

Section: Introductionmentioning

confidence: 99%

“…1,5 Moreover, Bn, C and S might play a defensive role in plants that produce them given their antimicrobial, anti-herbivory and allelopathic properties. 1,5 Interestingly, in only a few plant species, S and Bn are simultaneously present 4,5 and, perhaps for that reason, there are just a few methods for the analysis of these alkaloids in a single chromatographic run. Methods for the analysis of BIA's include chromatographic separation using paper or silica plates (TLC), as well as non-polar columns for liquid chromatography (HPLC).…”

Section: Introductionmentioning

confidence: 99%

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HPLC-DAD determination of berberine, chelerythrine and sanguinarine in the mexican prickly poppy (Argemone mexicana L. Papaveraceae), a medicinal plant

Xool-Tamayo¹,

Graniel-Sabido²,

Mirón-López³

et al. 2017

Quim. Nova

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A sensitive, simple, rapid and reliable HPLC-DAD method for the analysis of the benzylisoquinoline alkaloids (BIA's) content in Argemone mexicana (Papaveraceae) is presented. This method allows the simultaneous separation and quantitation of berberine (Bn), chelerythrine (C) and sanguinarine (S) in extracts from A. mexicana tissues, reducing time of analysis in comparison to previous reports. Alkaloids were separated on a C18 Hypersil Gold column using an acetonitrile gradient (20 to 70%) in 1% acetic acid in water. Alkaloids were identified based on retention times and UV spectra and quantified at 254 nm. Linearity between 0.5-20 µg mL -1 was observed for Bn, C and S, with limits of detection (LOD) and quantitation (LOQ) of 0.11 and 0.33 for Bn, 0.10 and 0.30 for C and 0.05 and 0.15 for S, respectively. Maximal intra-and inter-day variation values were < 0.49% in all cases, with alkaloids' recoveries higher than 95%. System suitability tests (SST), including resolution (Rs), retention factor (K'), selectivity (a), tailing factor and number of theoretical plates were performed according to the United States Pharmacopeia (USP), fulfilling recommended values. The method proved to be efficient and reproducible when analyzing different tissues of field-collected A. mexicana plants.

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Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension

Cited by 354 publications

References 10 publications

Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress

HPLC-DAD determination of berberine, chelerythrine and sanguinarine in the mexican prickly poppy (Argemone mexicana L. Papaveraceae), a medicinal plant

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