Abstract
Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).
Bauhiniastatin-1 alleviates diet induced obesity and lipid accumulation through modulating PPAR-γ/AMPK expressions: In-vitro, in-vivo and in-silico studies.