Anti-Obesity and Lipid Lowering Activity of Bauhiniastatin-1 is Mediated Through PPAR-γ/AMPK Expressions in Diet-Induced Obese Rat Model

Abstract

Objective: To evaluate the therapeutic efficacy and underlying molecular mechanisms of Bauhiniastatin-1 (BSTN1) to alleviate adiposity in diet-induced obese rodent model and in 3T3-L1 cells.Methods: BSTN1 was purified and confirmed through HPLC. In-vitro experiments such as MTT assay, Oil Red-O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis were performed in 3T3-L1 cells in the presence and absence of BSTN1. In animal experiments, rats were divided into Group-I: normal pellet diet-fed, Group-II: HFD-fed, Groups-III, IV and V: HFD-fed BSTN1 (1.25, 2.5, and 5 mg/kg.b.wt./day/rat)-treated and Group-VI: HFD-fed Orlistat-treated. The rats were fed either normal diet or high fat diet (HFD) for 18 weeks and water ad-libitum. BSTN1 was orally administered from 13th week onwards to the selected HFD-fed groups. Body composition parameters, biochemical assays, histopathology examination and western blot analysis were performed to identify the predicted targets related to obesity. Molecular docking studies threw light on the binding interactions of BSTN1 against PPAR-γ, FAS and AMPK.Results: BSTN1 at 20 μM significantly (p < 0.001) inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells. A conspicuous down-regulation in the mRNA expression levels of PPAR-γ, FAS and SREBP1 was observed but AMPK expression remained unchanged in BSTN1 treated 3T3-L1 cells. A substantial decrease in body weight gain, fat percent, total body fat, serum and liver lipid profile (except high-density lipoprotein), glucose, insulin and insulin resistance in BSTN1 treated rats was noticed in a dose dependent manner. In BSTN1 (5 mg/kg.b.wt.)-treated groups significantly (p < 0.01) elevated plasma adiponectin level but reduced leptin level as well as fall in serum AST and ALT were noticed. Further, the disturbed structural integrity and architecture of adipose and hepatic tissues due to high fat diet feeding were considerably recovered with BSTN1 treatment. Down-regulation in the protein expression level of PPAR-γ and activation of AMPK through phosphorylation was observed in BSTN1 treated rats than the untreated. Molecular docking studies revealed strong binding interactions of BSTN1 against PPAR-γ and AMPK and thus supported the experimental results.Conclusion: Taken together, the results suggest that BSTN1 could be a promising pharmacological molecule in the treatment of obesity and dyslipidemia.

Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model

“…The inhibition of fatty acid synthase was observed in other Cornus studies [57,93]. The relatively small decrease in FAS that we observed, despite a relevant increase in PPAR-α and decrease in SREBP-1c, may be because applying the cornelian cherry extract also contributed to an augmentation in LXR-α, which can stimulate FAS directly and indirectly [94], and PPAR-γ, the expression of which shows a positive correlation with FAS activity [95,96].…”

Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA‐MB‐231 and MCF‐7 breast cancer cells, an in‐vitro and in silico studies

“…Doxorubicin (0.5 μM) was used as the standard drug; all experiments were carried out in triplicate. The relative cytotoxicity was calculated using untreated control cells as the starting point 17 . The IC 50 values are determined by solving for the concentration of the tested substance in terms of the percent of inhibition closest to 50.…”

Biogenic Phytochemicals Modulating Obesity: From Molecular Mechanism to Preventive and Therapeutic Approaches

“…The antiobesity effects of these compounds are mediated by the regulation of various pathways, including lipid absorption, intake, and expenditure of energy, increasing lipolysis, and decrease lipogenesis, and differentiation and proliferation of preadipocytes as shown in Figure 1 [ 15 ]. A good number of phytoconstituents such as guggulsterone, hydroxycitric acid, apigenin, genistein, gymnemic acid, caffeine, theophylline, ephedrine, capsaicin, piperine, ellagic acid, and catechins have been reported to possess antilipidaemic and prohealth properties [ 15 , 20 , 21 ]. Although some of these compounds are used in preparing antiobesity drugs/formulations, they lack adequate clinical investigations and scientific validation to be authentic and recommended for obesity therapy.…”