Title : Combination of Scutellaria baicalensis and metformin ameliorates diet-induced metabolic dysregulation in mice via the gut-liver-brain axis
Abstract:
Background and Purpose: In conventional medicine, metformin (MF) is considered as the first-line drug for the treatment of type 2 diabetes (T2D). In traditional Oriental medicine, Scutellaria baicalensis (SB) is also commonly used to treat metabolic diseases. This study was conducted to investigate the effects of co-treatment with SB and MF, which may produce a potential beneficial effect on high-fat and high-fructose diet-induced metabolic dysregulation. Experimental
Methods: In order to achieve greater therapeutic response of SB and MF combination, first we optimized the dose of SB using four different doses (100, 200, 400 and 800 mg/kg) with a fixed dose of MF (200 mg/kg) in high- fat and high-fructose diet (HFFD)-induced C57BL6J mice. Next, the optimized dose of SB (400 mg/kg) was co-administered with various doses of MF (50, 100 and 200 mg/kg) to the same animal model to find the effective combinations of SB and MF. To explore the possible molecular mechanisms underlying the beneficial impact of these combinations and their association with gut microbial population, metabolic markers were determined in serum and tissues using different assays, histology, and gene expression, and gut microbial population were analyzed in week-12 stool samples using T-RFLP.
Results: The SB and MF co-treatment for 12-weeks significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPARγ, and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart, and the Bacteroidetes/ Firmicutes ratio was significantly increased in response to SB and MF co-treatment.
Conclusion: Taken together, the results of this study indicate that SB and MF co-treatment is an effective therapeutic approach for high-fat and high- carbohydrate diet-induced metabolic dysregulation which is operated through the gutliver-brain axis.
