DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis

Background The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza , is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity. Methods In vitro , investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50 mg/kg or 100 mg/kg) for 10 weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3 + V4 regions via pyrosequencing. Results DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis. Conclusions DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis. General significance DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals.