Danning tablets alleviate high fat diet-induced obesity and fatty liver in mice via modulating SREBP pathway

Ethnopharmacological relevance The traditional Chinese formula Danning tablets exhibit wide clinical applications in liver and gallbladder diseases, and currently it is reported to be effective on fatty liver disease in clinical trials. However, the underlying mechanisms remain elusive. Aim of the study The purpose of the present study was to assess the effects and potential pharmacological mechanisms of Danning tablet against high fat diet (HFD)-induced obesity, fatty liver, and related metabolic disorders in mice. Materials and methods C57BL/6 J male mice were treated with HFD for 12 weeks to trigger obesity and fatty liver condition. Then those mice were randomly divided into 5 groups, namely HFD, Danning tablet (0.75, 1.5 or 3 g/kg bodyweight) or lovastatin (30 mg/kg bodyweight) for extra 6 weeks’ treatment of HFD. Food intake and bodyweight were recorded each week. In the last week, before the mice were sacrificed, fasting blood glucose levels and insulin levels were measured. Furthermore, insulin and glucose tolerance tests were performed. Blood and hepatic lipid levels were examined, the lipid metabolism-associated gene expressions and protein levels in the liver or adipose tissues were assayed after sacrificing all mice. Results Our results demonstrated that a high dose of Danning tablet (3 g/kg) treatment mitigated body weight gain, reduced blood and hepatic cholesterol and triglyceride levels. The morphology analysis showed that Danning tablets could reduce lipid accumulation in both liver and brown adipose tissue. Moreover, Danning tablets could improve fasting blood glucose levels and ameliorate glucose and insulin tolerance in HFD-induced obese mice. Furthermore, qRT-PCR analysis revealed that the mRNA expressions of SREBP-1 and SREBP-2 as well as their target genes were remarkedly down-regulated in the liver and adipose tissue of diet-induced obesity (DIO) mice after treating those mice with Danning tablets. Conclusion Our results indicated that Danning tablets could improve the obesity-induced metabolic associated fatty liver disease (MAFLD) and related metabolic disorders. The potential mechanism may probably involve the regulation of the SREBP pathway.