目的:运用网络药理学方法和分子对接技术研究沙棘黄酮抗动脉粥样硬化(atherosclerosis, AS)的核心成分和作用机制。方法:通过TCMSP数据库查找沙棘有效成分与靶点,通过Genecards和OMIM数据库搜集AS靶点,利用Venny 2.1获得交集靶点,采用Cytoscape 3.7.2绘制PPI网络,运用Metascape平台对筛选到的靶点进行GO功能分析和KEGG通路富集分析;最后应用AutoDock和PyMOL软件进行分子对接。结果:筛选出11个活性成分,224个靶点,与AS交集靶点80个,GO功能分析得到共有条目5 242个,KEGG通路分析富集在234个通路上,其中流体剪切应力与动脉粥样硬化通路、PI3K-Akt信号通路和VEGF信号通路等为关键通路。分子对接结果显示沙棘主要活性成分槲皮素、异鼠李素和豆甾醇与靶点IL1β、PPARG、ADRB2和NOS3对接较好。结论:沙棘中黄酮类物质槲皮素和异鼠李素可能通过调控流体剪切应力与动脉粥样硬化通路、PI3K-Akt信号通路和VEGF信号通路等,作用于IL1β、PPARG、ADRB2、NR3C1和NOS3等相关枢纽靶点,从而起到抗炎、调节氧化应激及脂代谢紊乱,修复血管损伤等而达到抗AS的功效,这为后续基础研究提供了理论依据。
王晓雪
,
于建兵
,
刘琬瑜
,
王艳
,
王顺哲
,
赵婧
,
田昕益
,
薛永志
,
张东
. 基于网络药理学探讨沙棘黄酮抗动脉粥样硬化分子机制*[J]. 包头医学院学报, 2025
, 41(8)
: 22
-27
.
DOI: 10.16833/j.cnki.jbmc.2025.08.005
Objective: To study the core components and mechanism of sea buckthorn flavonoids anti-atherosclerosis (anti-AS) by network pharmacology and molecular docking technology. Methods: The active components and targets of Sea buckthorn were searched by TCMSP database, AS targets were collected by Genecards and OMIM database, intersection targets were obtained by Venny 2.1, and PPI networks were mapped by Cytoscape 3.7.2. GO function analysis and KEGG pathway enrichment analysis were performed on the selected targets using Metascape platform. Finally, AutoDock and PyMOL software were used for molecular docking. Results: 11 active ingredients, 224 targets and 80 intersection targets with AS were selected. A total of 5 242 items were identified by GO functional analysis, and 234 pathways were enriched by KEGG pathway analysis, among which fluid shear stress and atherosclerosis pathway, PI3K-Akt signaling pathway and VEGF signaling pathway were key pathways. Molecular docking results showed that the main active components of sea buckthorn quercetin, isorhamnetin and stigasterol had good docking with the target IL1β, PPARG, ADRB2 and NOS3. Conclusion: Quercetin and isorhamnetin in sea buckthorn may act on IL1β, PPARG, ADRB2, NR3C1 and NOS3 targets of fluid shear stress and atherosclerosis pathway, PI3K-Akt signaling pathway and VEGF signaling pathway, thus, it can achieve anti-AS effect by anti-inflammation, regulating oxidative stress, lipid metabolism disorders, and repairing vascular damage, etc., which provides a theoretical basis for subsequent basic research.
[1] 国家药典委员会.中华人民共和国药典: 一部[M]. 北京: 中国医药科技出版社, 2020.
[2] 田茜, 何晨, 贺敬霞, 等. 沙棘总黄酮-聚乙烯吡咯烷酮K30固体分散体的制备, 表征及体外溶出研究[J].中国药房, 2017, 28(1): 115-118.
[3] Pop RM, Socaciu C, Pintea A, et al. UHPLC/PDA-ESI/MS analysis of the main berry and leaf flavonol glycosides from different Carpathian Hippophaë rhamnoides L. varieties[J]. Phytochem Anal, 2013, 24(5): 484-492.
[4] 张东, 邬国栋. 沙棘黄酮的化学成分及药理作用研究进展[J]. 中国药房, 2019, 30(9): 1292-1296.
[5] Nelson AJ, Bubb K, Nicholls SJ. An update on emerging drugs for the treatment of hypercholesterolemia[J]. Expert Opin Emerg Drugs, 2021, 26(4): 363-369.
[6] 吴希泽, 康健, 李越, 等. 基于“浊气归心, 淫精于脉”理论运用HPLC-Q-TOF-MS/MS和网络药理学探讨抵挡汤防治动脉粥样硬化和高脂血症的作用机制[J]. 中国中药杂志, 2023, 48(5): 1352-1369.
[7] Lara-Guzman OJ, Tabares-Guevara JH, Leon-Varela YM, et al. Proatherogenic macrophage activities are targeted by the flavonoid quercetin[J]. J Pharmacol Exp Ther, 2012, 343(2): 296-306.
[8] Luo Y, Sun G, Dong X, et al. Isorhamnetin attenuates atherosclerosis by inhibiting macrophage apoptosis via PI3K/AKT activation and HO-1 induction[J]. PLoS One, 2015, 10(3): e0120259.
[9] Feng S, Dai Z, Liu AB, et al. Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2018, 1863(10): 1274-1284.
[10] Jayaraman A, Htike TT, James R, et al. TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus[J]. Acta Neuropathol Commun, 2021, 9(1): 159.
[11] Ren K, Li H, Zhou HF, et al. Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1[J]. Aging (Albany NY), 2019, 11(23): 10992-11009.
[12] Camps SGJA, Verhoef SPM, Bouwman FG, et al. Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity[J]. Gene X, 2019, 18(3): 100019.
[13] 李静雅. 糖皮质激素受体基因多态性与脑小血管病的相关性研究[D]. 唐山: 华北理工大学, 2019.
[14] 孙婷, 池晴佳, 王贵学. NOS3参与心血管疾病调控机制研究进展[J].生物医学工程学杂志, 2016, 33(1): 188-192.
[15] 曹珊, 张艺嘉, 白杨, 等. 基于消斑通脉方抗动脉粥样硬化作用机制的网络药理学分析和体外实验验证[J].吉林大学学报(医学版), 2024, 50(4): 925-938.
[16] Baeyens N, Bandyopadhyay C, Coon BG, et al. Endothelial fluid shear stress sensing in vascular health and disease[J]. J Clin Invest, 2016, 126(3): 821-828.
[17] Ma L, Zhang R, Li D, et al. Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway[J]. Chem Biol Interac, 2021, 349: 109659.
[18] Lu XL, Zhao CH, Yao XL, et al. Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway[J]. Biomed Pharmacother, 2017, 85: 658-671.
[19] Jia Q, Cao H, Shen D, et al. Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1[J]. Int J Mol Med, 2019, 44(3): 893-902.
[20] Luo Y, Sun G, Dong X, et al. Isorhamnetin attenuates atherosclerosis by inhibiting macrophage apoptosis via PI3K/AKT activation and HO-1 induction[J]. PLoS One, 2015, 10(3): e0120259.
[21] Liu J, Xu P, Liu D, et al. TCM regulates PI3K/Akt signal pathway to intervene atherosclerotic cardiovascular disease[J]. Evid Based Complement Alternat Med, 2021, 2021(1): 4854755.
