Sanhuang Xiexin Decoction ameliorates lipid disorders in obese mice via inducing browning of white adipose tissue and activating brown adipose tissue

BACKGROUND: Obesity has become a critical public health challenge worldwide. Prioritizing prevention and tackling root causes-rather than merely managing symptoms-is critical to curbing this pandemic. Strategies that activate and expand brown adipose tissue and beige adipose tissue increase energy expenditure in animal models and offer therapeutic promise to treat obesity. Sanhuang Xiexin Decoction (SHX) is a well-known traditional Chinese medicine that possesses several beneficial effects, including anti-inflammatory and anti-atherosclerotic properties. This study aims to investigate whether SHX can alleviate obesity by promoting the browning process in adipose tissue. METHODS: UPLC MS/MS was used to detect the constituents of SHX extraction, as well as the absorbed components of SHX in rat plasma. In vivo, C57BL/6 J mice were fed with 60% calorie high-fat diet for 8 weeks to induce obesity. 3T3-L1 white adipocyte and HIB-1B brown adipocyte were cultured. Parameters of body weight, food intake, Lee's index, skin temperature, adipose tissue mass, and blood glucose and lipids of mice were detected. The histological features of BAT and iWAT were observed by H&E staining, and the protein expression of UCP1 in adipose tissue was detected by immunohistochemistry method, and the UCP1 protein expression of 3T3-L1 and HIB-1B cells was tested using immunofluorescence staining. Gene expression of browning markers (e.g. Ucp1, Pgc1α, Prdm16, Cidea, Cd137, Tbx1, and Tmem26), fatty acid oxidation factors (e.g. Cpt-1β, Cyto-c, and Fatp1) and mitochondrial biogenic transcription factors (e.g. Nrf1, Nrf2, and Tfam) of adipose tissue, 3T3-L1 and HIB-1B cells was detected using qRT-PCR method. RESULTS: A total of 58 chemical components of Sanhuang Xiexin Decoction were identified by UPLC-LTQ-Orbitrap-MS(n) method, which provided the basis for the basic research of SHX pharmacodynamic substances. In vivo, SHX extraction could reduce body weight gain, improve glucose and lipid metabolism, enhance the activity of brown adipose tissue and induce the development of brown-like adipocytes of iWAT in obese mice. Furthermore, SHX extraction improved the gene expression of brown markers including Ucp1, Pgc1α and Prdm16, and mitochondrial biogenic transcription factors including Nrf1 and Tfam, as well as the UCP1 protein levels in white and brown adipocytes. CONCLUSIONS: Our study suggested that Sanhuang Xiexin Decoction could be used as a potential therapeutic candidate for the treatment of obesity and its complications by inducing browning of white adipose tissue and activating brown adipose tissue.