Ligusticum chuanxiong prevents high-fat-diet-induced lipid metabolism disorder in mice by modulating the genes in the cholesterol pathway

Ligusticum chuanxiong (LC) has been widely used for cardiovascular and cerebrovascular diseases. LC Hort extraction (LCE) can regulate high-fat-diet (HFD)-induced lipid metabolic disorders (LMDs). However, the potential mechanism of LCE alleviates LMDs has not been entirely determined. This study aimed to investigate the potential effect of LCE in regulating LMDs and reveal its intervention mechanism. LCE was used as the alternative constituent to intervene in HFD-induced LMDs. LCE antioxidant activity, toxicity, and the effects on serum lipid metabolism index were also determined. The potential intervention mechanism was investigated using the transcriptome analysis. Results confirmed that LCE administration remarkably decreased mice body weight, serum lipid indexes (total cholesterol [TC], triglyceride, low-density lipoprotein cholesterol, nonesterified fatty acid, and total bile acid), and liver malondialdehyde levels. LCE intervention increased the serum high-density lipoprotein cholesterol concentration and LPS enzyme activities, and LCE was nontoxic. The liver antioxidantive enzymes, such as catalase, superoxide dismutase, glutathione, lipoprotein lipase, and hepatic lipase, were enhanced. RNA-seq Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis confirmed that LCE was mainly involved in the lipid metabolism-related signaling pathways, especially for cholesterol biogenesis and metabolic signaling pathways. Besides, genes, such as Cyp51, Msoml, Apof, Pmvk, Nsdh1, ApoA-1, ApoC-1, and Lcat, might have been upregulated, thus further inhibiting cholesterol synthesis. By upregulating genes related to the bile acid signaling pathway, such as CYP7A1, CYP27A1, and ABCG5/8, the conversion of TC into bile acid was accelerated, and cholesterol levels decreased. LCE could serve as an alternative Chinese medicine for alleviating HFD-induced LMDs symptoms through multichannel interactions. This study provides a reference for exploring new functions of LC, especially for regulating LMDs.