[Hepatic lipidomics and metabolomics unveil hypolipidemic mechanism of Arisaematis Rhizoma].

This study aimed to elucidate the mechanism of Arisaematis Rhizoma in improving hyperlipidemia through hepatic lipidomics and metabolomics. Forty-eight SPF-grade male SD rats were randomly divided into six groups(n=8 per group): control group, model group, positive control group(fenofibrate, 40 mg·kg~(-1)), high-dose Arisaematis Rhizoma group(A-H, 2.8 g·kg~(-1)), medium-dose Arisaematis Rhizoma group(A-M, 1.4 g·kg~(-1)), and low-dose Arisaematis Rhizoma group(A-L, 0.7 g·kg~(-1)). The intervention lasted for 4 consecutive weeks. Serum lipid levels were detected by biochemical analysis. Pathological morphology and lipid deposition were observed by hematoxylin-eosin(HE) and oil red O staining. The mechanism underlying the hypolipidemic effect of Arisaematis Rhizoma was analyzed via hepatic lipidomics and metabolomics. The mRNA expression of key targets and key enzyme levels were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and enzyme-linked immunosorbent assay(ELISA), respectively. A-H exhibited significantly ameliorated dyslipidemia, improved hepatic pathological injury, and reduced lipid accumulation in liver tissue. Hepatic lipidomic and metabolomic results showed that A-H corrected the metabolic profile in the liver of hyperlipidemic rats, with 30 and 44 differential metabolites significantly reversed, respectively. Pathway enrichment analysis revealed that Arisaematis Rhizoma exerted its hypolipidemic effect by regulating glycerophospholipid metabolism, linoleic acid metabolism, arachidonic acid metabolism, alpha-linolenic acid metabolism, glycine, serine, and threonine metabolism, primary bile acid biosynthesis, fatty acid degradation, galactose metabolism, steroid hormone biosynthesis, and D-amino acid metabolism. Combined with molecular biology experiments, the results indicated that Arisaematis Rhizoma improved hyperlipidemia by regulating hepatic lipid metabolic disorders(e.g., phospholipid remodeling), inhibiting cholesterol synthesis, promoting cholesterol decomposition, and modulating key targets peroxisome prociferator-activated receptor-α(PPAR-α)/liver X receptor-α(LXR-α). These findings provide experimental evidence for the clinical application of Arisaematis Rhizoma in resolving phlegm.