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

Abstract

Background S. baicalensis , 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 S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. Materials and Methods The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis 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 S. baicalensis 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 S. baicalensis is involved to regulate lipid metabolism. Conclusion According to our metabolomics results, S. baicalensis 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 S. baicalensis , 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 S. baicalensis on lipid metabolism using network pharmacology and lipidomics.

Mechanisms of Banxia Xiexin Decoction Underlying Chronic Atrophic Gastritis via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations

“…Nevertheless, in comparison with the precise clinical efficacy and the long history of the application of TCM, there is a relative lack of research on the mechanism of TCM. Accordingly, considering the multicomponent and multitarget characterization of TCM, the method of network pharmacology has been applied to study the potential mechanism of TCM and a series of progress was accomplished [ 40 , 41 ]. In our current study, we initially explored the potential mechanism of BXD on CAG via the method of network pharmacology considering the definitive clinical efficacy of BXD.…”

Baicalin ameliorates Mycoplasma gallisepticum-induced inflammatory injury via inhibiting STIM1-regulated ceramide accumulation in DF-1 cells

“…It has been reported that baicalin can regulate lipid metabolism, oxidative stress, calcium homeostasis and endoplasmic reticulum stress of host ( Cao et al, 2018 ; Ishfaq et al, 2019a ; Wang et al, 2020 ; Yu et al, 2020 ). For example, according to a network pharmacology study, S. baicalensis may exert its beneficial effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways of host, and baicalin, a major ingredient of S. baicalensis , may regulate lipid metabolism by inhibiting activities of key enzymes such as squalene monooxygenase and lanosterol synthase ( Ge et al, 2021 ). In addition, baicalin can alleviate oxidative stress and endoplasmic reticulum stress via Nrf2 signaling pathway activation ( Lin et al, 2014 ).…”

Network Pharmacology and Molecular Docking Analyses Unveil the Mechanisms of Yiguanjian Decoction against Parkinson’s Disease from Inner/Outer Brain Perspective

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