[Mechanism of vitexin in treating acute hyperlipidemia by combination of metabolomics and network pharmacology].
Source: PubMed, NCBI / U.S. National Library of Medicine
The study aims to investigate the mechanism of vitexin in treating acute hyperlipidemia through a combination of network pharmacology, molecular docking, and metabolomics approaches. An acute hyperlipidemia mouse model was established in mice by intramuscular injection of tyloxapol(Triton WR-1339). By using network pharmacology, the core target of vitexin in hyperlipidemia treatment was identified, and its binding affinity with the core target and stability were assessed through molecular docking. The screened core targets were validated through animal experiments to confirm their lipid-lowering effects. Serum metabolomics analysis was conducted by using ultra-performance liquid chromatography-quadrupole-time-of-flight high-resolution mass spectrometry(UPLC-Q-TOF-MS/MS) to screen differential metabolites and enrich key metabolic pathways. A total of 41 core potential targets, including serine-threonine protein kinase 1(namely AKT1), Toll-like receptor 4(TLR4), and myeloid differentiation primary response protein 88(MYD88), were screened through network pharmacology. The primary regulatory pathways included the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT), nuclear factor-κB(NF-κB), and other signaling pathways. Molecular docking analyses demonstrate that vitexin exhibits a strong binding affinity for TLR4, MYD88, PI3K, and AKT. Animal studies demonstrate that vitexin can significantly ameliorate abnormal lipid metabolism in mice and reduce the levels o
Abstract
The study aims to investigate the mechanism of vitexin in treating acute hyperlipidemia through a combination of network pharmacology, molecular docking, and metabolomics approaches. An acute hyperlipidemia mouse model was established in mice by intramuscular injection of tyloxapol(Triton WR-1339). By using network pharmacology, the core target of vitexin in hyperlipidemia treatment was identified, and its binding affinity with the core target and stability were assessed through molecular docking. The screened core targets were validated through animal experiments to confirm their lipid-lowering effects. Serum metabolomics analysis was conducted by using ultra-performance liquid chromatography-quadrupole-time-of-flight high-resolution mass spectrometry(UPLC-Q-TOF-MS/MS) to screen differential metabolites and enrich key metabolic pathways. A total of 41 core potential targets, including serine-threonine protein kinase 1(namely AKT1), Toll-like receptor 4(TLR4), and myeloid differentiation primary response protein 88(MYD88), were screened through network pharmacology. The primary regulatory pathways included the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT), nuclear factor-κB(NF-κB), and other signaling pathways. Molecular docking analyses demonstrate that vitexin exhibits a strong binding affinity for TLR4, MYD88, PI3K, and AKT. Animal studies demonstrate that vitexin can significantly ameliorate abnormal lipid metabolism in mice and reduce the levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in serum. Additionally, vitexin lowers the levels of TC, TG, aspartate aminotransferase(AST), and alanine aminotransferase(ALT) in the liver, alleviates liver pathological damage, and mitigates lipid accumulation. Furthermore, it downregulates the mRNA expressions of PI3K, AKT, NF-κB, tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-1β. Metabolomics identified a total of 68 differential metabolites, predominantly found in six metabolic pathways: arginine and proline metabolism, tryptophan metabolism, arginine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, arachidonic acid metabolism, and alpha-linolenic acid metabolism. In summary, vitexin can ameliorate abnormal lipid metabolism in mice with acute hyperlipidemia. The mechanism may be related to its modulation of the PI3K/AKT/NF-κB signaling pathway and various metabolic pathways, offering a theoretical basis and guidance for the action mechanism investigation of vitexin.