Integrating Network Pharmacology and Experimental Validation to Elucidate the Mechanism Underlying Ligusticum...

Ligusticum Chuanxiong (LC), as a raw material of food and medicinal homologous, was shown to reduce lipid accumulation and modulate gene expression associated with lipid metabolism in high-fat diet (HFD)-fed mice, but its underlying alleviating mechanism of alleviating hyperlipidemia symptoms has not been systematically evaluated. This study aims to assess its potential mechanism by combining a computer-aided screening strategy with in vivo analysis. Results revealed that LC compounds could participate in the regulation of 40 potential hub targets related to hyperlipidemia. Besides, Kyoto Encyclopedia of Genes and Genomes analysis showed the screened hub targets were mainly enriched in the signaling pathways of lipid metabolism, inflammation, and immunomodulation. Molecular docking results demonstrated that LC compounds could bind to the amino acid residues of the hub targets (β-2 adrenergic receptor, tumor necrosis factor, peroxisome proliferator-activated receptor gamma [PPARG], vascular endothelial growth factor R, estrogen receptor 1 [ESR1], and prostaglandin G/H synthase 1/2 [PTGS1/2]) in the mode of hydrogen-bond and hydrophobic interaction with low binding energy. Meanwhile, in vivo experiments with mice and transcriptome analysis demonstrated that the administration of LC extract had a beneficial impact on addressing HFD-induced hyperlipidemia induced by, particularly in regulating the genes ESR1, PPARG, and PTGS1/2. This study provides a scientific basis for LC compounds in the intervention of hyperlipidemia.