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整合网络药理学探讨洋川芎内酯A诱导肝星状细胞衰老缓解肝纤维化作用及机制

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中草药 | 中药防治器官纤维化研究 2026,57(18): 7124-7137

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中草药 |中药防治器官纤维化研究 2026 , 57 (18) : 7124 -7137

整合网络药理学探讨洋川芎内酯A诱导肝星状细胞衰老缓解肝纤维化作用及机制

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董明行¹, 李晓骄阳¹, 霍子璇¹, 李佳楠¹, 王馨¹, 杨紫涵¹, 唐恺悦¹, 曲姣蓉¹

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通讯作者:

曲姣蓉

作者简介:

董明行: 董明行，硕士研究生，研究方向为中药及天然产物防治肝纤维化。E-mail:15870998858@163.com

Effect and mechanism of senkyunolide A against liver fibrosis via inducing hepatic stellate cell senescence using integrated network pharmacology

DONG Minghang¹, LI Xiaojiaoyang¹, HUO Zixuan¹, LI Jianan¹, WANG Xin¹, YANG Zihan¹, TANG Kaiyue¹, QU Jiaorong¹

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doi: 10.7501/j.issn.0253-2670.2026.18.005

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目的于体内外水平探讨洋川芎内酯A（senkyunolide A，SenA）通过诱导肝星状细胞（hepatic stellate cells，HSCs）衰老以改善肝纤维化的作用机制。方法利用SwissTargetPrediction数据库和GeneCards数据库获得SenA靶点及肝纤维化疾病相关靶点，取二者交集进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。应用Metascape分析蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络，筛选并确认核心靶点，针对核心靶点开展功能富集分析，并将核心靶点与SenA进行分子对接。采用胆总管结扎术建立肝纤维化小鼠模型，分别采用转化生长因子-β1（transforming growth factor-β1，TGF-β1）和血小板衍生生长因子-BB（platelet-derived growth factor-BB，PDGF-BB）诱导建立人源肝星状LX-2细胞和大鼠肝星状HSC-T6细胞活化模型，给予SenA干预后，结合衰老相关β-半乳糖苷酶（senescence-associated-β-galactosidase，SA-β-Gal）染色、EdU染色、qRT-PCR等表征衰老指标。结果网络药理学结果显示，SenA与肝纤维化有39个交集靶点，交集靶点富集于细胞衰老相关通路。进一步基于PPI网络获得19个基因可能是SenA调控肝纤维化进展的核心靶点，并发现与细胞衰老相关的核心靶点在HSCs中高表达。结合分子对接实验，发现SenA与Aurora激酶A（Aurora kinase A，AURKA）的结合能力最强，提示AURKA可能是SenA在HSCs发挥作用的关键分子靶点。体内外实验结果显示，SenA显著诱导HSCs的衰老（P＜0.05、0.01、0.001），显著下调增殖相关基因细胞周期蛋白D1（Cyclin D1，CCND1）和周期蛋白依赖性激酶2（cyclin-dependent kinase 2，CDK2）的表达（P＜0.05、0.01），同时上调衰老相关基因p21、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白细胞介素-6（interleukin-6，IL-6）的表达（P＜0.05、0.01），进而显著抑制HSCs活化与胶原沉积（P＜0.05、0.01、0.001）。结论 SenA通过诱导HSCs衰老以抑制HSCs活化，从而改善肝纤维化。

关键词

洋川芎内酯A / 衰老 / 肝纤维化 / 肝星状细胞 / 衰老相关分泌表型

Abstract

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Objective To explore the mechanisms by which by which senkyunolide A (SenA) ameliorated liver fibrosis via inducing hepatic stellate cells (HSCs) senescence in vitro and in vivo. Methods SenA targets and liver fibrosis related targets were obtained using the SwissTargetPrediction database and GeneCards database. The intersection targets were used for gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Metascape was used to analyze protein-protein interaction (PPI) network, core targets were screened and confirmed, functional enrichment analysis on core targets was performed, and molecular docking with SenA was performed. A mouse model of liver fibrosis was established using common bile duct ligation. Human hepatic stellate LX-2 cells and rat hepatic stellate HSC-T6 cells were induced using transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB), respectively. After SenA intervention, senescence indicators were characterized by senescence-associated-β-galactosidase (SA-β-Gal) staining, EdU staining, qRT-PCR, etc. Results The results of network pharmacology revealed that SenA and liver fibrosis shared 39 common targets, the common target genes were enriched in cellular senescence pathways. A total of 19 genes obtained based on PPI network may be the core targets of SenA on regulation of liver fibrosis progression, and it was found that core targets related to cellular aging are highly expressed in HSCs. Combining molecular docking experiments, it was found that SenA had the strongest binding ability to Aurora kinase A (AURKA), suggesting that AURKA may be a key molecular target for SenA in HSCs. The results of in vivo and in vitro experiments showed that SenA significantly induced HSCs senescence (P < 0.05, 0.01, 0.001), significantly downregulated the expressions of proliferation related genes Cyclin D1 (CCND1) and cyclin dependent kinase 2 (CDK2) (P < 0.05, 0.01), and upregulated the expressions of senescence related genes p21, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (P < 0.05, 0.01), thereby significantly inhibiting HSC activation and collagen deposition (P < 0.05, 0.01, 0.001). Conclusion SenA induces HSC senescence to inhibit HSC activation, thereby improving liver fibrosis.

Key words

senkyunolide A / senescence / liver fibrosis / hepatic stellate cells / senescence associated secretory phenotypes

引用本文

董明行, 李晓骄阳, 霍子璇, 李佳楠, 王馨, 杨紫涵, 唐恺悦, 曲姣蓉. 整合网络药理学探讨洋川芎内酯A诱导肝星状细胞衰老缓解肝纤维化作用及机制. 中草药, 2026 , 57 (18) : 7124 -7137 . DOI: 10.7501/j.issn.0253-2670.2026.18.005

DONG Minghang, LI Xiaojiaoyang, HUO Zixuan, LI Jianan, WANG Xin, YANG Zihan, TANG Kaiyue, QU Jiaorong. Effect and mechanism of senkyunolide A against liver fibrosis via inducing hepatic stellate cell senescence using integrated network pharmacology[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (18) : 7124 -7137 . DOI: 10.7501/j.issn.0253-2670.2026.18.005

基金

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国家自然科学基金青年项目 (82404984); 中央高校基本科研业务费专项资金 (2024-JYB-JBZD-055)

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2026年第57卷第18期

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doi: 10.7501/j.issn.0253-2670.2026.18.005

接收时间：2026-06-12
首发时间：2026-10-29

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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