Benefits of Huang Lian mediated by gut microbiota on HFD/STZ-induced type 2 diabetes mellitus in mice

Abstract

BackgroundHuang Lian (HL), one of the traditional Chinese medicines (TCMs) that contains multiple active components including berberine (BBR), has been used to treat symptoms associated with diabetes for thousands of years. Compared to the monomer of BBR, HL exerts a better glucose-lowering activity and plays different roles in regulating gut microbiota. However, it remains unclear what role the gut microbiota plays in the anti-diabetic activity of HL.MethodsIn this study, a type 2 diabetes mellitus (T2DM) mouse model was induced with a six-week high-fat diet (HFD) and a one-time injection of streptozotocin (STZ, 75 mg/kg). One group of these mice was administrated HL (50 mg/kg) through oral gavage two weeks after HFD feeding commenced and continued for four weeks; the other mice were given distilled water as disease control. Comprehensive analyses of physiological indices related to glycolipid metabolism, gut microbiota, untargeted metabolome, and hepatic genes expression, function prediction by PICRUSt2 were performed to identify potential mechanism.ResultsWe found that HL, in addition to decreasing body fat accumulation, effectively improved insulin resistance by stimulating the hepatic insulin-mediated signaling pathway. In comparison with the control group, HL treatment constructed a distinct gut microbiota and bile acid (BA) profile. The HL-treated microbiota was dominated by bacteria belonging to Bacteroides and the Clostridium innocuum group, which were associated with BA metabolism. Based on the correlation analysis, the altered BAs were closely correlated with the improvement of T2DM-related markers.ConclusionThese results indicated that the anti-diabetic activity of HL was achieved, at least partly, by regulating the structure of the gut microbiota and the composition of BAs.

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome

“…Berberine treatment (100 mg/kg/day) caused the enrichment of total bile acids (BAs) in the gut content of HFD hamsters and the improvement of glucolipid dysfunction, which was ascribed to the elevated expression of Cytochrome P450 (CYP) 7A1 and CYP27A1 in hepatic cells 27 . Moreover, a similar upregulation of genes Cyp7a1 and Cyp27a1 was observed in an HFD/streptozotocin (STZ)‐induced T2DM model with Huang Lian treatment 28 …”

“…27 Moreover, a similar upregulation of genes Cyp7a1 and Cyp27a1 was observed in an HFD/streptozotocin (STZ)-induced T2DM model with Huang Lian treatment. 28 Microbial enzymes are required for the conversion of the BA pool. For instance, bile salt hydrolase (BSH) is involved in the transformation from conjugated BAs into unconjugated BAs.…”

“…In diabetic mouse models, Huang Lian treatment upregulated cbh gene and bai operons, which were involved in the deconjugation and dehydroxylation of BAs, respectively 28 . In PCOS rats, the Clostridium , which was associated with the generation of BSH, was significantly altered after BBR treatment 66 .…”

“…In diabetic mouse models, Huang Lian treatment upregulated cbh gene and bai operons, which were involved in the deconjugation and dehydroxylation of BAs, respectively. 28 In PCOS rats, the Clostridium, which was associated with the generation of BSH, was significantly altered after BBR treatment. 66 69 Elevated LPS and inflammatory factors activated the LPS/NF-κB, NLRP3 inflammasome and MAPK signalling pathway, while BBR administration inhibited those pro-inflammatory pathways and ameliorated the inflammatory state of ovaries in PCOS rats.…”

Updated Progress on Polysaccharides with Anti-Diabetic Effects through the Regulation of Gut Microbiota: Sources, Mechanisms, and Structure–Activity Relationships

“…Inactivation of the PI3K/Akt signaling pathway in liver reduces the synthesis of liver glycogen, resulting in insulin resistance, a typical symptom of T2DM [ 173 ]. The phosphorylation of ISR1, PI3K and Akt in succession activates GLUT4/GLUT2, leading to glucose uptake of cells [ 174 ]. Many polysaccharides relieve the symptoms of DM by regulating the PI3K/Akt signal pathway.…”