Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Drug Des Devel Ther. 2021 May 4;15:1915-1930. doi: 10.2147/DDDT.S301679. eCollection 2021.
, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer's disease.
To elucidate the mechanism by which modulates lipid metabolism and explore the medicinal effects of at a holistic level.
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.
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.
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.
黄芩作为一种传统草药，在治疗与异常脂质代谢相关的疾病方面具有巨大潜力，如炎症、高脂血症、动脉粥样硬化和阿尔茨海默病。
阐明黄芩调节脂质代谢的作用机制，并从整体水平探索黄芩的药用功效。
采用网络药理学方法，鉴定黄芩调节脂质代谢的潜在活性成分及相关靶点。利用代谢组学比较黄芩处理后脂质变化，以鉴定出显著变化的代谢物，并通过分子对接验证关键靶点和化合物。
类固醇生物合成、鞘脂代谢、PPAR 信号通路和甘油酯代谢等被富集并预测为黄芩作用的潜在通路。进一步的代谢组学检测显示，鉴定出 14 种差异显著的代谢物，这些代谢物与脂质代谢有关。对代谢物进行通路富集分析后，鉴定出胆固醇代谢和鞘脂代谢为最相关的通路。基于通路分析结果，认为黄芩调节脂质代谢的关键途径包括鞘脂和胆固醇生物合成以及甘油磷脂代谢。
根据我们的代谢组学结果，黄芩可能通过调节胆固醇生物合成和鞘脂代谢通路发挥其治疗作用。进一步分析某些通路中改变的代谢物，发现角鲨烯下游的药物明显上调；然而，SQLE 的底物却出人意料地增加。通过分子对接的综合证据，我们推测黄芩的主要成分黄芩苷可能通过抑制胆固醇生物合成途径中的 SQLE 和 LSS 来抑制胆固醇的生物合成。综上所述，本研究通过网络药理学和脂质组学为黄芩在脂质代谢方面的治疗作用提供了新的见解。
