Potential Mechanism of on Lipid Metabolism Explored via Network Pharmacology and Untargeted Lipidomics.

BACKGROUND

, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer's disease.

AIM OF THE STUDY

To elucidate the mechanism by which modulates lipid metabolism and explore the medicinal effects of at a holistic level.

MATERIALS AND METHODS

The potential active ingredients of and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking.

RESULTS

Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which is involved to regulate lipid metabolism.

CONCLUSION

According to our metabolomics results, may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of , may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of on lipid metabolism using network pharmacology and lipidomics.