Berberine in type 2 diabetes therapy: a new perspective for an old antidiarrheal drug?

Zhang, Ming; Chen, Li

doi:10.1016/j.apsb.2012.06.004

Cited by 39 publications

(38 citation statements)

References 42 publications

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“…These data indicated that miRNA-27a and miRNA-27b markedly regulated the differentiation induced by berberine in 3T3-L1 cells and that berberine exerts an antidifferentiation activity that is associated with the upregulation of miRNA-27a and miRNA-27b. Previously, berberine upregulated the expression levels of two C/EBP inhibitors, CCAAT-enhancer-binding protein homologous protein (CHOP) and differentially expressed in chondrocytes-2, while it downregulated C/EBPα, PPARγ and other adipogenic markers and effectors in differentiating 3T3-L1 pre-adipocytes and mature adipocytes (28). Additionally, the antiadipogenic activity of berberine was notably diminished by knockdown of CHOP expression or by adjusting the differentiation culture media (12).…”

Section: Discussionmentioning

confidence: 99%

Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells in response to berberine

Huang

et al. 2016

Molecular Medicine Reports

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Berberine is the major active component of Rhizoma Coptidis derived from a traditional Chinese herbal medicine and is known to regulate micro (mi)RNA levels, although the mechanism for this action remains unknown. The present study confirmed that treatment of 3T3‑L1 cells with berberine inhibited cell viability and differentiation in a dose‑ and time‑dependent manner, and significantly increased the mRNA expression levels of miRNA‑27a and miRNA‑27b. In addition, in 3T3‑L1 cells treated with berberine, overexpression of miRNA‑27a and miRNA‑27b improved the berberine-mediated inhibition of cell differentiation and reduction of triglyceride contents. By contrast, miRNA‑27a and miRNA‑27b inhibitors attenuated the berberine‑mediated inhibition of cell differentiation and reduction of triglyceride contents. Additionally, peroxisome proliferator‑activated receptors (PPAR)‑γ was confirmed to be a target of miRNA‑27a in the 3T3‑L1 cells. A dual‑luciferase reporter assay indicated that the expression of PPAR‑γ was negatively regulated by miRNA-27a. These findings may provide novel mechanistic insight into the antiobesity effects of certain compounds in traditional Chinese herbal medicine.

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Section: Discussionmentioning

confidence: 99%

Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells in response to berberine

Huang

et al. 2016

Molecular Medicine Reports

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“…1) (17,18). Previous studies have suggested that the protoberberine alkaloids have multiple pharmacological functions, including the ability to improve glycemic control and lipid profile, as well as antibiotic, anti-inflammatory, anti-diarrheal, antineoplastic, antiarrhythmic and immunosuppressive properties (19)(20)(21)(22)(23). Although the pharmacological effects of BER and other Coptis extracts have been widely reported, information regarding their oral absorption remains to be fully elucidated.…”

Section: Introductionmentioning

confidence: 95%

Poor permeability and absorption affect the activity of four alkaloids from Coptis

Cui

Zhang

Wang

et al. 2015

Molecular Medicine Reports

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Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra‑performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil‑water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P‑glycoprotein (P‑gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l‑1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0‑1.2x10‑6 cm·s‑1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical‑to‑basolateral (AP‑BL) surface and the basolateral‑to‑apical (BL‑AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BL‑AP surface was significantly faster (P<0.01), compared with that on the AP‑BL surface and, following the addition of verpamil (a P‑gp inhibitor), the Papp (AP‑BL) of the four alkaloids increased, whereas the Papp (BL‑AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER was significantly higher, compared with the three other alkaloids. Furthermore, the A % and Ka provided evidence that the absorption of BER was increased in the jejunum, compared with in the ileum. In conclusion, the four alkaloids from Coptis appeared to be poorly absorbed, determined using a shake flask, pre‑coated PAMPA plates, a Caco‑2 cell monolayer model and intestinal perfusion; however, absorption was higher in the jejunum than in the ileum. Among the four alkaloids, the permeability of BER was markedly higher than the others, and P‑gp efflux had a significant effect on the absorption of those alkaloids.

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“…Berberine has been reported to have antibacterial/anti-parasitic properties and anti-oxidative/ anti-inflammatory activities (Ni et al 2015). Recently, human and animal studies indicated that berberine also had a hypoglycemic activity (Zhang & Chen 2012) and an extra-beneficial protection for cardiovascular system in hypertension or diabetes (Wang et al 2012, Li et al 2014, Ni et al 2015. Our previous work observed that berberine alleviated cerebral arterial contractility in streptozotocin (STZ)-induced diabetic rats by regulating the intracellular Ca 2+ handling of smooth muscle cells (Ma et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Berberine reduced blood pressure and improved vasodilation in diabetic rats

Liang

Zhang

et al. 2017

Journal of Molecular Endocrinology

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Hyperglycemia and hypertension are considered to be the two leading risk factors for vascular disease in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and hypertension at the same time in diabetes. The objectives of this study are to investigate whether berberine treatment could directly reduce blood pressure and identify the molecular mechanism underlying the vascular protection of berberine in diabetic rats. Berberine was intragastrically administered with different dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the injection of streptozotocin. The endothelium-dependent/-independent relaxation in middle cerebral arteries was investigated. The activity of large-conductance Ca-activated K channel (BK) was investigated by recording whole-cell currents, analyzing single-channel activities and assessing the expressions of α- and β1-subunit at protein or mRNA levels. Results of the study suggest that chronic administration of 100 mg/kg/day berberine not only lowered blood glucose but also reduced blood pressure and improved vasodilation in diabetic rats. Furthermore, berberine markedly increased the function and expression of BK β1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from diabetic rats or when exposed to hyperglycemia condition. The present study provided initial evidences that berberine reduced blood pressure and improved vasodilation in diabetic rats by activation of BK channel in VSMCs, which suggested that berberine might provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated that activation of BK channel might be the underlying mechanism responsible for the vascular protection of berberine in diabetes.

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Berberine in type 2 diabetes therapy: a new perspective for an old antidiarrheal drug?

Cited by 39 publications

References 42 publications

Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells in response to berberine

Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells in response to berberine

Poor permeability and absorption affect the activity of four alkaloids from Coptis

Berberine reduced blood pressure and improved vasodilation in diabetic rats

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