Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

Abstract

Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine) and control group. Fasting blood glucose (FBG), weight, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT) was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR) index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4), mitogen-activated protein kinase 14 (MAPK14), MAPK8(c-jun N-terminal kinase, JNK), peroxisome proliferator-activated receptor α (PPARα), uncoupling protein 2 (UCP2), and hepatic nuclear factor 4α(HNF4α), whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP), PPARγ coactivator 1α(PGC 1α), and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK-) p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

Improvement of superoxide dismutase and catalase in streptozotocin–nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide

“…Neither berberine nor glibenclamide showed a negative effect on the blood glucose AUC level of the normal mice (Table 2). These observations supported the hypoglycemic potential of berberine on the DM type 2 (Lao-ong et al, 2012;Zhang et al, 2008Zhang et al, , 2011.…”

“…Extensive research has shown the pharmacological activities of berberine, in which the well known benefit of berberine is hypoglycemic action. Zhang et al (2008Zhang et al ( , 2011 reported that berberine at a daily dose of 1.0 g for 3 months was effective and safe for the treatment of diabetes mellitus (DM) and dyslipidemia in human. Chronic DM results in several complications such as hypertension, heart attack, kidney failure and finally, morbidity or premature death.…”

Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis)

“…Berberine has been shown to exert a large number of effects on cellular machinery; including the reduction of F-actin polymerization [51], moderation of lipid and glucose metabolism [52], direct binding to polyadenylic acid [53], and modulation of MAP family kinase activity [54]. To gain insight into the effect of berberine on the growth of influenza A, we focused our studies on the production of viral proteins.…”

Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies

“…In KK-Ay mice, a model of diabetes with obesity, BBR treatment reduces fasting blood glucose, fasting serum insulin levels and HOMA-IR, improves glucose tolerance and reduces TC and TG by modulating several pathways [53]. In addition, BBR inhibits the expression of pro-inflammatory genes in the adipose tissue of obese mice, indicating that BBR may attenuate both the acute inflammatory response and the low-grade inflammatory status typical of obesity [55].…”