Multi-omics reveals the role of PPARα signaling in the treatment of hyperlipidemia with Qinlian Hongqu Decoction

Qinlian Hongqu Decoction (QLHQD), a traditional Chinese herbal formula, exerts therapeutic effects on high-fat diet (HFD)-induced lipid metabolism disorders, but its underlying mechanisms remain unclear. This study aimed to investigate QLHQD's efficacy in treating hyperlipidemia and clarify its potential mechanisms. The chemical components of QLHQD were identified by ultra-performance liquid chromatography (UPLC). A hyperlipidemic rat model was established via HFD feeding, and the effects of QLHQD on serum lipids, hepatic steatosis, inflammation, oxidative stress, and gut microbiota were evaluated using automatic biochemical analysis, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, oil red O staining, reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and 16S rDNA amplicon sequencing. Transcriptomics, network pharmacology, metabolomics, molecular docking, and molecular dynamics simulations were integrated to explore mechanisms, with key proteins validated by Western blot (WB) and IHC. Seven QLHQD components were identified; animal experiments showed QLHQD reduced serum lipids, hepatic steatosis, inflammation, and oxidative stress, and regulated gut microbiota in hyperlipidemic rats. Integrated transcriptomics and network pharmacology revealed significant enrichment of the peroxisome proliferator-activated receptor α (PPARα) signaling pathway, and molecular docking confirmed strong affinity between all seven QLHQD components and PPARα protein. WB, IHC, and metabolomics verified that QLHQD likely ameliorates HFD-induced dyslipidemia and hepatic steatosis by regulating bile acid metabolism via the PPARα pathway. In conclusion, QLHQD effectively alleviates HFD-induced dyslipidemia and hepatic steatosis in hyperlipidemic rats, with the underlying mechanism possibly associated with regulating the PPARα-bile acid metabolism pathway.