Efeito antioxidante e antiobesidade da silimarina (Silybum marianum L.) em modelo de obesidade induzida por dieta hipercalórica em camundongos C57BL/6

Abstract

Obesity is a health problem associated to fat accumulation, which leads to oxidative stress and inflammation, described as key-factors on its pathway and related comorbidities. Despite that, the current pharmacotherapy is still limited, onerous and neglects oxidative stress and inflammation. In this context, flavonoids have shown potential as anti-obesity drugs, such as silymarin (S. marianum L.), a flavonoid-rich extract used as

hepatoprotector due its antioxidant properties. Then, this work aimed to evaluate anti- obesity effect of silymarin in a high-fat diet-induced (HFD) obesity model. For this,

C57BL/6 male mice received HFD for 55 days. Groups were treated with silymarin (100, 10 and 1 mg/kg) or orlistat (30 mg/kg). Body weight (BW), food and water intake were measured daily, and on the last day, plasma, adipose and hepatic tissue were collected. As results, HFD induced obesity in untreated animals, while animals treated with silymarin presented reduced gain of BW about 40%, which was correlated with reduced mass of hepatic and adipose tissues, and deposition of triglycerides. Silymarin was able to improve lipid metabolism and hepatic function reducing plasmatic cholesterol, triglycerides, and transaminases levels. Silymarin caused reduction on TBARS levels and increasement of GSH and superoxide dismutase activity on both adipose and hepatic tissues. Additionally, silymarin was able to prevent IL-1β production and release in hepatic and adipose tissue, as well as maintained adiponectin levels in adipose tissue. Furthermore, molecular docking simulations were performed with pancreatic lipase target, showing the possible interactions with residues from the catalytic site and other important regions of this enzyme. In conclusion, the results showed that silymarin antioxidant and anti-inflammatory effects improved lipid metabolism which leads to reduced deposition of triglycerides in hepatic and adipose tissues, and reduction of body weight.