-
舒肝宁注射液是在中国传统医学经典方剂——张仲景《伤寒杂病论》“茵陈蒿汤”基础上进一步研发的纯中药注射剂,由茵陈、栀子、黄芩、板蓝根和灵芝等五味中药材的提取物组合而成,在临床上主要用于治疗急慢性病毒性肝炎、药物性肝炎、胆汁淤积性肝炎等肝脏疾病[1-2]。舒肝宁注射液所含中药种类繁多,化学成分复杂,其改善肝炎的有效成分及相应的作用机制尚不清楚,因此,研究舒肝宁注射液的有效活性成分、作用靶点及其抗炎保肝的作用机制具有重要的科学意义。
中药复方活性成分不明是中药复方药效物质基础研究的瓶颈之一,网络药理学通过将化学成分映射到疾病基因网络中来寻找潜在的生物活性成分,为筛选中药活性成分提供了一种方法。同时以中药成分、靶点和疾病等数据相关信息为基础,构建生物网络,通过网络分析阐释中药的作用机制,对中药复方在临床应用具有重要的意义。
本研究通过检索TCMSP数据库以及相关文献收集舒肝宁注射液的活性成分信息,并在此基础上利用药物靶点分析平台STITCH预测舒肝宁注射液可能的作用靶点,采用Cytoscape构建舒肝宁注射液抗肝炎作用的“活性成分-作用靶点”网络,对这些靶点进行蛋白-蛋白相互作用分析,利用DAVID数据库进行基因功能和信号通路分析,探讨舒肝宁注射液抗炎保肝作用可能的作用机制。
Study on the mechanism of anti-inflammatory and hepatoprotective effects of Shuganning injection based on network pharmacology
-
摘要:
目的 构建舒肝宁注射液活性成分-作用靶点和蛋白相互作用网络,探讨舒肝宁注射液抗炎保肝作用机制。 方法 通过TCMSP数据库获取舒肝宁注射液中茵陈、栀子、黄芩、板蓝根和灵芝的主要活性成分;利用GeneCard和OMIM数据库筛选舒肝宁注射液活性成分对应靶点中与肝炎相关靶点;采用Cytoscape构建活性成分-作用靶点网络;应用String数据库和Cytoscape软件绘制蛋白相互作用网络;通过DAVID数据库对靶点进行GO及KEGG通路分析。 结果 筛选得到舒肝宁注射液活性成分20个,共83个作用靶点。GO分析表明,舒肝宁注射液主要影响细胞过程和生物过程的调控,以及对化学刺激和应激的反应等作用。KEGG通路分析显示,舒肝宁注射液抗炎保肝作用的靶点主要涉及TNF、IL-17、MAPK等信号通路。 结论 舒肝宁注射液的抗炎保肝作用具有多成分、多靶点、多通路的特点,可能通过调节TNF、IL-17、MAPK等通路发挥作用。 Abstract:Objective To explore the anti-inflammatory and hepatoprotective mechanism of Shuganning injection through establishing the active ingredients-targets network and protein interactions network. Methods The main active ingredients of Artemisiae scopariae, Fructus gardenia, Radix scutellariae, Radix isatidis and Ganoderma in Shuganning injection were obtained by TCMSP; GeneCards and OMIM were used to screen the hepatitis-related targets among the corresponding targets of the active ingredient of Shuganning injection; The Cytoscape software was used to construct the active ingredient-targets network of Shuganning injection. The protein interactions network was constructed using the String database and Cytoscape software. The GO and KEGG pathways involved in the targets were analyzed by DAVID database. Results The results showed that 20 active ingredients and 83 targets of Shuganning injection were involved. GO analysis showed that Shuganning injection mainly affected the regulation of cellular processes and biological processes, as well as the response to chemical stimulation and stress. KEGG pathway analysis showed that the targets of the anti-inflammatory and hepatoprotective effect of Shuganning injection mainly involved in signaling pathways such as TNF, IL-17, and MAPK. Conclusion The anti-inflammatory and hepatoprotective effect of Shuganning injection have the characteristics of multiple components, multiple targets and multiple pathways, which may play a role by regulating pathways such as TNF、IL-17 and MAPK . -
-
[1] 陈明泉, 李谦, 张琼华, 等. 舒肝宁注射液治疗急慢性病毒性肝炎的临床疗效观察[J]. 肝脏, 2007, 12(3):194-196. doi: 10.3969/j.issn.1008-1704.2007.03.014 [2] 张瑾. 舒肝宁注射液对顺铂中毒小鼠肝脏损伤的保护作用[J]. 中国药房, 2016, 27(7):920-922. doi: 10.6039/j.issn.1001-0408.2016.07.17 [3] 汝锦龙. 中药系统药理学数据库和分析平台的构建和应用[D]. 咸阳: 西北农林科技大学, 2015. [4] 王艳春, 王建强. 舒肝宁注射液临床应用研究进展[J]. 中国药物警戒, 2020, 17(8):543-548. doi: 10.19803/j.1672-8629.2020.08.20 [5] 刘媛媛, 刘陶, 吴玉梅, 等. 基于雌激素受体调节Nrf2-ARE通路的黄芩中抗氧化成分的筛选[J]. 中国药理学通报, 2019, 35(6):822-827. doi: 10.3969/j.issn.1001-1978.2019.06.017 [6] 朱悦. 异欧前胡素激活LXRα/β介导HMGB1-NLRP3炎症信号通路改善肝纤维化进程的研究[D]. 延吉: 延边大学, 2021. [7] 陈丹. 山奈酚的抗炎镇痛作用及其机制研究[D]. 南京: 南京中医药大学, 2021. [8] 郭媛媛, 任锋, 张向颖, 等. 山奈酚对内质网应激诱导的肝细胞损伤的保护及机制[J]. 世界华人消化杂志, 2014, 22(35):5400-5407. [9] 刘鸣昊, 张丽慧, 马庆亮, 等. 槲皮素对非酒精性脂肪性肝炎大鼠的影响[J]. 中成药, 2019, 41(8):1820-1825. doi: 10.3969/j.issn.1001-1528.2019.08.014 [10] PANDITH H, ZHANG X B, THONGPRADITCHOTE S, et al. Effect of Siam weed extract and its bioactive component scutellarein tetramethyl ether on anti-inflammatory activity through NF-κB pathway[J]. J Ethnopharmacol,2013,147(2):434-441. doi: 10.1016/j.jep.2013.03.033 [11] 樊江波, 黄琳红. 益母草活性成分芫花素对小鼠凝血及抗炎作用的研究[J]. 西安交通大学学报(医学版), 2019, 40(1):158-161. [12] GAO Q, ZHU H W, DONG L Q, et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma[J]. Cell,2019,179(5):1240. doi: 10.1016/j.cell.2019.10.038 [13] LONG J Y, WANG A Q, BAI Y, et al. Development and validation of a TP53-associated immune prognostic model for hepatocellular carcinoma[J]. EBioMedicine,2019,42:363-374. doi: 10.1016/j.ebiom.2019.03.022 [14] TOK Y T, ŞENER A G, GÖKMEN A A, et al. Investigation of regulatory T cells and secreted immunomodulatory cytokine IL-10 levels in patients with hepatitis B[J]. Mikrobiyol Bul,2020,54(2):266-278. doi: 10.5578/mb.69340 [15] HE G B, KARIN M. NF-κB and STAT3 - key players in liver inflammation and cancer[J]. Cell Res,2011,21(1):159-168. doi: 10.1038/cr.2010.183 [16] MIZUTANI T, SHINODA M, TANAKA Y, et al. Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2[J]. Drug Metab Rev,2005,37(1):235-252. doi: 10.1081/DMR-200028798 [17] CHEN X P, WANG H J, XIE W M, et al. Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China[J]. Pharmacogenet Genomics,2006,16(3):219-227. doi: 10.1097/01.fpc.0000194424.20393.c6 [18] SALUM G M, BADER EL DIN N G, IBRAHIM M K, et al. Vascular endothelial growth factor expression in hepatitis C virus-induced liver fibrosis: a potential biomarker[J]. J Interferon Cytokine Res,2017,37(7):310-316. doi: 10.1089/jir.2016.0127 [19] DU T, GUO X H, ZHU X L, et al. Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population[J]. J Viral Hepat,2006,13(9):618-624. doi: 10.1111/j.1365-2893.2006.00731.x [20] EL-KASHEF D H, ABDELRAHMAN R S. Montelukast ameliorates Concanavalin A-induced autoimmune hepatitis in mice via inhibiting TNF-α/JNK signaling pathway[J]. Toxicol Appl Pharmacol,2020,393:114931. doi: 10.1016/j.taap.2020.114931 [21] ZHANG H Y, BERNUZZI F, LLEO A, et al. Therapeutic potential of IL-17-mediated signaling pathway in autoimmune liver diseases[J]. Mediators Inflamm,2015,2015:436450. [22] CHANG M L, YEH C T, CHIEN R N, et al. Overt acute hepatitis B deteriorates in females: destructive immunity with an exaggerated interleukin-17 pathway[J]. Front Immunol,2021,12:631976. doi: 10.3389/fimmu.2021.631976 [23] HENNIG B J, FIELDING K, BROXHOLME J, et al. Host genetic factors and vaccine-induced immunity to hepatitis B virus infection[J]. PLoS One,2008,3(3):e1898. doi: 10.1371/journal.pone.0001898 [24] OFFICE F E. Retraction: microRNA-155 modulates hepatic stellate cell proliferation, apoptosis, and cell cycle progression in rats with alcoholic hepatitis via the MAPK signaling pathway through targeting SOCS1[J]. Front Pharmacol,2022,12:840009. doi: 10.3389/fphar.2021.840009