Integrative multi-omics reveals that Pueraria thomsonii Radix alleviates dyslipidemia by remodeling gut microbiota and regulating arachidonic acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria thomsonii Radix (PTR, "Fen-ge") is a food-medicine herb widely used in China for metabolic complaints. Its putative lipid-modulating effects are supported by traditional practice, but the molecular basis remains incompletely understood.

AIM OF THE STUDY: To elucidate the active constituents and mechanisms by which PTR mitigates dyslipidemia.

MATERIALS AND

METHODS

Chemical profiling and plasma exposure of PTR constituents were characterized by UPLC-Q-TOF-MS/MS. A high-fat-diet rat model was used to assess pharmacodynamic endpoints including serum lipid panel, hepatic histopathology, liver injury markers and inflammatory cytokines. Untargeted plasma metabolomics was performed in rats and patients; rat fecal 16S rRNA gene sequencing and hepatic transcriptomics complemented mechanism inference. Multivariate models were cross-validated and FDR-controlled; pathway and multi-omics correlation analyses integrated metabolite-microbe-gene relationships.

RESULTS

PTR significantly ameliorated dyslipidemia in high-fat diet-fed rats, as evidenced by improved serum lipid profiles, reduced ALT/AST levels, and alleviated hepatic steatosis and inflammation in histopathological examination. Integrated metabolomic analysis across rats and patients revealed that the restored metabolic pathways were primarily concentrated in arachidonic acid and unsaturated fatty acid metabolism. Gut microbiota analysis indicated that PTR remodeled microbial taxa correlated with arachidonic acid-related lipid metabolism. Meanwhile, hepatic transcriptomics data showed that differentially expressed genes were functionally enriched in biological processes such as lipid oxidation and were bioinformatically linked to the AMPK signaling pathway.

CONCLUSIONS

PTR may ameliorate dyslipidemia through coordinated modulation of the gut microbiota and arachidonic acid metabolic network. Based on integrated omics analysis, the hepatic AMPK signaling pathway may potentially be involved in this regulatory process; however, its direct mechanistic role requires further experimental validation. Future investigations employing targeted lipid-omics, protein phosphorylation assays, and microbiota-transfer experiments are warranted to elucidate the causal relationships.