| 引用本文: | 高亮,张亚琳,武雨含,邵佳慧,张慧,邵益丹,许亚萍,蒋剑平.基于网络药理学研究新“浙八味”衢枳壳黄酮抗肝细胞癌的作用机制[J].中国现代应用药学,2024,41(2):166-176. |
| GAO Liang,ZHANG Yalin,WU Yuhan,SHAO Jiahui,ZHANG Hui,SHAO Yidan,XU Yaping,JIANG Jianping.Study on the Mechanism of the Flavonoids from the New "Zhe Eight Flavors" Quzhou Fructus Aurantii Against Hepatocellular Carcinoma Based on Network Pharmacology[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(2):166-176. |
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| 基于网络药理学研究新“浙八味”衢枳壳黄酮抗肝细胞癌的作用机制 |
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高亮1,2, 张亚琳2, 武雨含2, 邵佳慧2, 张慧1, 邵益丹3, 许亚萍4, 蒋剑平2,5
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1.浙江工业大学药学院，杭州 310014;2.浙大城市学院医学院，杭州 310015;3.杭州市西溪医院，杭州 310023;4.浙江中医药大学附属第一医院(浙江省中医院)，杭州 310006;5.浙大城市学院附属医院，杭州 311300
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| 摘要: |
| 目的 基于网络药理学预测并通过实验验证新“浙八味”衢枳壳黄酮类活性成分抗肝细胞癌的作用机制。方法 通过TCMSP、TCMID、ETCM、BATMAN-TCM及SwissTargetPrediction数据库收集衢枳壳黄酮类化合物(包括柚皮苷、芸香柚皮苷、新橙皮苷)的潜在作用靶点；应用GeneCards、CTD、Disgenet和OMIM数据库构建肝细胞癌疾病靶点集；将衢枳壳黄酮潜在靶点与肝细胞癌靶点取交集以获取关键靶点蛋白，建立蛋白互作网络；对核心靶点进行GO 功能和KEGG 通路富集分析，并构建成分-靶点-通路-疾病网络；采用增殖、克隆、愈合与迁移试验分析衢枳壳黄酮对肝癌细胞HepG2活力的影响；使用荧光探针染色观察衢枳壳黄酮对HepG2细胞线粒体膜电位与凋亡的影响；运用RT-qPCR技术验证衢枳壳黄酮对网络药理学预测的关键靶点PRKCA的调控作用。结果 基于网络药理学筛选得到217个衢枳壳黄酮的作用靶点，与疾病靶点的交集靶点59个，涉及ALB、ESR1、PRKCA等。GO 功能与KEGG 通路富集分析显示，衢枳壳黄酮作用靶点共涉及193个生物学过程，13条癌症相关信号通路。实验结果表明衢枳壳黄酮能影响肝癌细胞的增殖、克隆、愈合与迁移能力，导致线粒体膜电位下降并促进细胞凋亡。RT-qPCR的结果表明衢枳壳黄酮能够显著下调PRKCA表达，验证了网络药理学的预测分析结果。结论 本研究揭示了衢枳壳黄酮通过PRKCA靶点治疗肝细胞癌的潜在分子作用机制，为其临床防治肝细胞癌的应用奠定基础。 |
| 关键词: 衢枳壳 黄酮 网络药理学 肝细胞癌 凋亡 PRKCA |
| DOI：10.13748/j.cnki.issn1007-7693.20232688 |
| 分类号:R285.5 |
| 基金项目:国家自然科学基金面上项目(82074186)；浙江省高层次人才“特支计划”青年拔尖人才项目(ZJWR0108035)；国家教育部产学合作协同育人项目 (202102242035)；杭州市医药卫生科技(重点)项目(ZD20230028)；浙江省中医药科技计划项目(2024ZF074)；浙江省教育厅一般科研项目(Y202352924) |
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| Study on the Mechanism of the Flavonoids from the New "Zhe Eight Flavors" Quzhou Fructus Aurantii Against Hepatocellular Carcinoma Based on Network Pharmacology |
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GAO Liang1,2, ZHANG Yalin2, WU Yuhan2, SHAO Jiahui2, ZHANG Hui1, SHAO Yidan3, XU Yaping4, JIANG Jianping2,5
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1.College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China;2.School of Medicine, Hangzhou City University, Hangzhou 310015, China;3.Hangzhou Xixi Hospital, Hangzhou 310023, China;4.The First Affliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China;5.Affiliated Hospital, Hangzhou City University, Hangzhou 311300, China
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| Abstract: |
| OBJECTIVE To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification. METHODS From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR. RESULTS Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis. CONCLUSION This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC. |
| Key words: Quzhou Fructus Aurantii flavonoids network pharmacology hepatocellular carcinoma apoptosis PRKCA |
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