Dingxin recipe III ameliorates hyperlipidemia injury in SD rats by improving the gut barrier, particularly the SCFAs/GPR43 pathway

Authors：Gu, Yu-yan; Cui, Xiao-bing; Jiang, Jing; Zhang, Ya-xin; Liu, Meng-hua; Cheng, Sai-bo; Li, Yu-ye; Liu, Lin -ling; Liao, Rong-xin; Zhao, Peng; Jin, Wen; Jia, Yu-hua^*; Wang, Jing^*; Zhou, Feng-hua^*

Source：Journal of Ethnopharmacology, 2023, 312: 116483.

DOI：10.1016/j.jep.2023.116483

• Hyperlipidemia
• Gut microbiota
• SCFAs
• Lipid metabolism
• DXR III

Ethnopharmacological relevance: Dingxin Recipe III (DXR III) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. Aim of the study: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR III in hyperlipidemia. Materials and methods: The bioactive compounds of DXR III were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respec-tively. The pharmacological mechanisms of DXR III were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. Results: DXR III treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR III improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR III also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR III downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR III and SCFAs upregulated the expression of colon ABCA1.Conclusion: DXR III protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.

• Institution
  广州中医药大学; 南方医科大学; 1