Network Pharmacology and Pharmacological Evaluation Reveals the Mechanism of the Sanguisorba Officinalis in Suppressing Hepatocellular Carcinoma.
Network Pharmacology and Pharmacological Evaluation Reveals the Mechanism of the Sanguisorba Officinalis in Suppressing Hepatocellular Carcinoma.
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网络药理及药理评价揭示地榆抑制肝癌的机制
DOI：
10.3389/fphar.2021.618522
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发表时间：
2021
影响因子：
5.6
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Jiang N;Li H;Sun Y;Zeng J;Yang F;Kantawong F;Wu J
背景：地桂是一种著名的中药，广泛用于治疗复杂疾病，如抗癌、抗菌、抗病毒、抗炎、抗氧化、止血等。尤其是已有报道在多种人类癌症中发挥抗肿瘤作用。然而，其对肝细胞癌的作用及其药理机制尚不清楚。方法：本研究采用网络药理学方法对SO等肝细胞癌的发病机制进行了研究。通过蛋白质相互作用(PPI)、基因本体论(GO)和途径富集化分析确定潜在靶点和信号转导途径。并构建了化合物-靶点和靶点-通路网络。随后，还进行了体外实验，以进一步验证SO对肝癌的抗癌作用。结果：通过综合网络药理学分析，从相应的数据库中收集到41种有效成分，根据口服生物利用度和类药物指数筛选出12种有效成分，预测了258个与肝癌相关的潜在靶点。通过富集分析发现，So通过多条途径对肝癌细胞显示出良好的治疗作用，主要通过EGFR、PI3K/AKT、NFκB和MAPK信号通路与肿瘤细胞的增殖和存活有关。此外，在体外，还发现SO对多种肝癌细胞具有抑制细胞增殖、诱导细胞凋亡、下调细胞迁移和侵袭的作用。免疫印迹分析显示，SO处理可下调p-EGFR、p-PI3K、p-AKT、p-NFMAPK B和p-κ蛋白的表达。这些结果表明，SO对肝癌的治疗作用主要是通过EGFR/MAPK和EGFR/PI3K/AKT/NFκB信号通路来调节细胞的增殖和存活。结论：综上所述，本研究从多靶点、多途径揭示了SO的抗肝癌作用及其潜在的治疗机制。
Background: Sanguisorba Officinalis L. (SO) is a well-known traditional Chinese medicine (TCM), commonly applied to treat complex diseases, such as anticancer, antibacterial, antiviral, anti-inflammatory, anti-oxidant and hemostatic effects. Especially, it has been reported to exert anti-tumor effect in various human cancers. However, its effect and pharmacological mechanism on hepatocellular carcinoma (HCC) remains unclear. Methods: In this study, network pharmacology approach was applied to characterize the underlying mechanism of SO on HCC. Active compounds and potential targets of SO, as well as related genes of HCC were obtained from the public databases, the potential targets and signaling pathways were determined by protein-protein interaction (PPI), gene ontology (GO) and pathway enrichment analyses. And the compound-target and target-pathway networks were constructed. Subsequently, in vitro experiments were also performed to further verify the anticancer effects of SO on HCC. Results: By using the comprehensive network pharmacology analysis, 41 ingredients in SO were collected from the corresponding databases, 12 active ingredients screened according to their oral bioavailability and drug-likeness index, and 258 potential targets related to HCC were predicted. Through enrichment analysis, SO was found to show its excellent therapeutic effects on HCC through several pathways, mainly related to proliferation and survival via the EGFR, PI3K/AKT, NFκB and MAPK signaling pathways. Additionally, in vitro, SO was found to inhibit cell proliferation, induce apoptosis and down-regulate cell migration and invasion in various HCC cells. Moreover, western blot analysis showed that SO treatment down-regulated the expression of p-EGFR, p-PI3K, p-AKT, p-NFκB and p-MAPK proteins in HepG2 cells. These results validated that SO exerted its therapeutic effects on HCC mainly by the regulation of cell proliferation and survival via the EGFR/MAPK and EGFR/PI3K/AKT/NFκB signaling pathways. Conclusion: Taken together, this study, revealed the anti-HCC effects of SO and its potential underlying therapeutic mechanisms in a multi-target and multi-pathway manner.
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影响因子：
2.4
作者：
Huynh H;Nguyen TT;Chow KH;Tan PH;Soo KC;Tran E
通讯作者：
Tran E
影响因子：
14.9
作者：
Li YH;Yu CY;Li XX;Zhang P;Tang J;Yang Q;Fu T;Zhang X;Cui X;Tu G;Zhang Y;Li S;Yang F;Sun Q;Qin C;Zeng X;Chen Z;Chen YZ;Zhu F
通讯作者：
Zhu F
互补的中草药疗法可改善台湾胰腺癌患者的生存：一项基于人群的同类研究。
影响因子：
2.9
作者：
Kuo YT;Liao HH;Chiang JH;Wu MY;Chen BC;Chang CM;Yeh MH;Chang TT;Sun MF;Yeh CC;Yen HR
通讯作者：
Yen HR
影响因子：
--
作者：
Han B;Yu YQ;Yang QL;Shen CY;Wang XJ
通讯作者：
Wang XJ
索拉非尼对亚太地区晚期肝细胞癌患者的疗效和安全性：一项 III 期随机、双盲、安慰剂对照试验
影响因子：
51.1
作者：
Cheng, Ann-Lii;Kang, Yoon-Koo;Guan, Zhongzhen
通讯作者：
Guan, Zhongzhen