广西师范大学学报（自然科学版） ›› 2021, Vol. 39 ›› Issue (5): 198-209.doi: 10.16088/j.issn.1001-6600.2020082201

• 研究论文 • 上一篇    下一篇

十大功劳甘草汤治疗肝炎的网络药理学研究

蒋向辉1*, 谭荣1, 杨永平2, 肖清淙1   

  1. 1.凯里学院 大健康学院,贵州 凯里 556011;
    2.贵州奥特药业有限公司,贵州 凯里 556011
  • 收稿日期:2020-08-22 修回日期:2020-11-02 出版日期:2021-09-25 发布日期:2021-10-19
  • 通讯作者: 蒋向辉(1974—),男,湖南安化人,凯里学院教授,博士。E-mail:jxfei789@163.com
  • 基金资助:
    贵州省科学技术基金(黔科合J字[2015]2131);贵州省科技厅社会发展项目(黔科合支撑[2018]2823)

Analysis of Network Pharmacology and Confirmation of Mahonia fortunei (Lindl. ) Fedde and Glycyrrhiza uralensis Fisch Decoction for Hepatitis

JIANG Xianghui1*, TAN Rong1, YANG Yongping2, XIAO Qingzong1   

  1. 1. College of Health, Kaili University, Kaili Guizhou 556011, China;
    2. Guizhou Oute Pharmaceutical Co. Ltd., Kaili Guizhou 556011, China
  • Received:2020-08-22 Revised:2020-11-02 Online:2021-09-25 Published:2021-10-19

PDF (PC)

98

摘要： 为了探讨十大功劳甘草汤治疗肝炎的潜在作用机制,借助中药系统药理学数据库TCMSP(traditional Chinese medicine systems pharmacology)对十大功劳和甘草的生物活性成分和潜在作用靶点进行预测,通过Cytoscape 3.6.1软件构建十大功劳甘草汤活性成分-靶点-疾病网络,利用OMIM(online mendelian inheritance in man)和GeneCards 数据库进行肝炎疾病作用相关靶点的筛选,通过PPI(protein-protein interaction network)分析数据库构造十大功劳甘草汤和肝炎交集蛋白的相互作用网络,通过Omicshare平台对核心靶点进行GO(gene ontology)分析,并对核心靶点进行KEGG(kyoto encyclopedia of genes and genomes)代谢通路分析。在对十大功劳甘草汤主要活性成分与作用靶点进行分子对接分析的基础上,通过十大功劳甘草水提物治疗乙酰氨基酚(APAP)诱导的急性肝损伤小鼠,测定血清中相关生化指标,探讨其活性成分的作用机制。结果表明:十大功劳甘草汤治疗肝炎的交集靶点蛋白有25个,其中核心靶点有12个;筛选出山柰酚、柚皮素和异鼠李素3种潜在的先导化合物及其作用蛋白前列腺素过氧化物合酶(PTGS);十大功劳甘草水提物、山柰酚、柚皮素和异鼠李素可显著降低肝损伤小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、嘌呤核苷磷酸化酶(PNP)和丙二醛(MDA)的含量,提高谷胱甘肽(GSH)和超氧化物岐化酶(SOD)含量;十大功劳甘草汤中的活性成分可能通过参与炎症因子氧化应激的调节而对抗肝损伤。

关键词: 网络药理学, 十大功劳, 甘草, 肝炎, 分子确证

Abstract: To explore the potential mechanism of Mahonia fortunei (Lindl.)Fedde and Glycyrrhiza uralensis Fisch decoction for hepatitis based on network pharmacology. TCMSP and TCMID databases are used to collect active ingredients and targets of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction, GeneCards and OMIM databases are used to screen for genes related to hepatitis and to intersect with the target genes of active ingredients in Perilla frutescens and Bidens pilosa L. decoction, a protein mutual network (PPI network) was built by the string website, and the biological process of the intersection target was analyzed by the Reactome database and the KEGG metabolic pathway analysis on the Omicshare platform. A component-target-channel network was built by Cytoscape software, screened core targets and core pathways by conducting network topology analysis method, the core target protein crystal structure was further imported into Autodock software to confirm the molecular docking of the active ingredient and the core target protein. By measuring the biochemical indicators in the acute liver injury model, the mechanism of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction for hepatitis were studied. The result showed that Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction contains 95 ingredients, including 872 potential targets. There are 198 targets related to hepatitis in Genecards and OMIM databases. 25 intersection targets were obtained by intersection analysis, and 12 core targets were further obtained from the drug-compound-target network graph. By molecular docking confirmation analysis, three potential lead compounds including Kaempferol, naringenin, and isorhamnetin were screened, and the potential target proteins were confirmed. The experimental results showed that the water extract of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch, kaempferol, naringenin and isorhamnetin can significantly reduce the content of ALT, AST, PNP and MDA in the serum of mice, and increase the content of GSH and SOD. The active ingredients in Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction may avoid liver injury by regulation of oxidative stress.

Key words: network pharmacology, Mahonia fortunei (Lindl.)Fedde, Glycyrrhiza uralensis Fisch, hepatitis, molecular confirmation

中图分类号: 

  • R285
[1] 马雪梅.感冒的预防及治疗[J].中国民族民间医药,2009,18(22):143.
[2] 周罗晶,欧爱华,高巨,等.广州某高校大学生普通感冒发生状况与心理压力关系的初步探讨[J].广东医学,2008,29(10):1729-1730.
[3] 龙运光,萧成纹,吴国勇,等.中国侗族医药[M]. 北京:中医古籍出版社,2011:69-70.
[4] 张业,邹碧群,方毅林,等. 十大功劳果实提取物抗氧化活性研究[J]. 广西师范大学学报(自然科学版),2011,29(1): 43-46.
[5] 刘靖丽,闫浩,王钰莹,等. 甘草皂苷类化合物结构与保肝活性关系的DFT 研究[J]. 天然产物研究与开发, 2020,32(9): 1515-1521.
[6] WU Z K, WANG Y, CHEN L N. Network-based drug repositioning[J]. Molecular BioSystems, 2013, 9(6): 1268-1281. DOI:10.1039/c3mb25382a.
[7] PAN L L, LI Z Z, WANG Y F, et al. Network pharmacology and metabolomics study on the intervention of traditional Chinese medicine Huanglian Decoction in rats with type 2 diabetes mellitus[J]. Journal of Ethnopharmacology, 2020, 258:112842. DOI:10.1016/j.jep.2020.112842.
[8] AHMED S S, RAMAKRISHNAN V. Systems biological approach of molecular descriptors connectivity: optimal descriptors for oral bioavailability prediction[J]. PLoS One, 2012, 7(7):e40654. DOI:10.1371/journal.pone.0040654.
[9] YU G H, ZHANG Y Q, REN W Q, et al. Network pharmacology-based identification of key pharmacological pathways of Yin-Huang-Qing-Fei capsule acting on chronic bronchitis[J]. International Journal of Chronic Obstructive Pulmonary Disease, 2016, 12(3): 85-94. DOI:10.2147/COPD.S121079.
[10] FAKURAZI S, HAIRUSZAH I, NANTHINI U. Moringa oleifera lam prevents acetaminophen induced liver injury through restoration of glutathione level[J]. Food and Chemical Toxicology, 2008, 46(8): 2611-2615. DOI:10.1016/j.fct.2008.04.018.
[11] LI X K, YANG H J, XIAO J C, et al. Network pharmacology based investigation into the bioactive compounds and molecular mechanisms of Schisandrae Chinensis Fructus against drug-induced liver injury[J]. Bioorganic Chemistry, 2020, 96:103553. DOI:10.1016/j.bioorg.2019.103553.
[12] 尹学哲,金延华,王玉娇,等. 草苁蓉不同溶剂萃取物对对乙酰氨基酚诱导的小鼠急性肝损伤的保护作用[J]. 中国药学杂志,2014,49(6): 469-472.
[13] 张雨,李恒,李克宁,等. 复方中药网络药理学的研究进展[J]. 中成药,2018, 40(7): 1584-1588.
[14] 邢心睿,吕狄亚,柴逸峰,等. 网络药理学在中药作用机制中的研究进展[J]. 药学实践杂志, 2018,36(2): 97-102.
[15] LIAO W Z, CHEN L Y, MA X, et al. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells[J]. European Journal of Medicinal Chemistry, 2016, 114:24-32. DOI:10.1016/j.ejmech.2016.02.045.
[16] 宋金玥,任锋,张向颖,等. 山奈酚干预对D-氨基半乳糖/脂多糖诱导小鼠急性肝衰竭的保护作用[J]. 中国中西医结合杂志,2017,37(5):569-574.
[17] GUO H Q, LIN W, ZHANG X Y, et al. Kaempferol induces hepatocellular carcinoma cell death via endoplasmic reticulum stress-CHOP-autophagy signaling pathway[J]. Oncotarget, 2017, 8(47): 82207-82216. DOI:10.18632/oncotarget.19200.
[18] KIM J K, PARK S U. Recent studies on kaempferol and its biological and pharmacological activities[J]. EXCLI Journal, 2020, 19: 627-634.
[19] REHMAN K, KHAN I I, AKASH S H, et al. Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia[J]. Journal of Food Biochemistry, 2020, 44(10):e13422. DOI:10.1111/jfbc.13422.
[20] 李沛波,王永刚,吴灏,等. 柚皮苷及其苷元柚皮素的呼吸系统药理作用研究概述[J]. 药学研究,2020,39 (5): 249-255.
[21] CHANG Z, WANG J L, JING Z C, et al. Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies[J]. Phytotherapy Research, 2020, 34(10): 2730-2744. DOI:10.1002/ptr.6714.
[22] GONG G, GUAN Y Y, ZHANG Z L. Isorhamnetin: a review of pharmacological effects[J]. Biomedicine and Pharmacotherapy, 2020, 128:110301. DOI:10.1016/j.biopha.2020.110301.
[23] WEI Q F, LV F, ZHANG H J, et al. MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2[J]. Bioscience Reports, 2020, 40(1):20191136. DOI:10.1042/BSR-20191136.
[24] 余秀婷. 广藿香和黄连主要活性成分抗炎症性肠病的作用和机制探讨[D]. 广州: 广州中医药大学,2016.
[25] WU J R, MIAO J, DING Y, et al. MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4[J]. Biochemistry and Cell Biology, 2019, 97(6): 722-730. DOI:10.1139/bcb-2019-0008.
[26] 马波江,曹晔,朱艳. 雌激素受体基因与微小RNA在冠心病中的相关性[J]. 中国老年学杂志, 2015,35(16): 4481-4483.
[27] 王晓慧. 雄激素对高盐饮食下大鼠血管内皮的影响及相关机制的探讨[D]. 苏州: 苏州大学,2013.
[28] KIM E H, LEE J S, LEE N R, et al. Regulation of constitutive neutrop apoptosis due to house dust mite allergen in normal and allergic rhinitis subjects[J]. PLoS One, 2014, 9(9):e105814. DOI:10.1371/journal.pone.0105814.
[29] YAMAMOTO T, YOSHIMURA M, YAMAGUCHI F, et al. Anti-allergic activity of naringenin chalcone from a tomato skin extract[J]. Bioscience Biotechnology and Biochemistry, 2004, 68(8): 1706-1711. DOI:10.1271/bbb.68.1706.
[1] 刘晶晶, 陈转欣, 尤佳航, 黄家艳, 程克光. 齐墩果酸-对羟基苯甲腈及其类似物的合成与抗肿瘤活性评价[J]. 广西师范大学学报（自然科学版）, 2021, 39(2): 132-138.
[2] 孙立, 初相伍, 刘春梅, 张琚政, 程克光. 熊果酸/甘草次酸-尿嘧啶核苷缀合物的合成与抗肿瘤活性评价[J]. 广西师范大学学报（自然科学版）, 2020, 38(1): 87-92.
[3] 黄东, 李跃林, 卜凯, 黄文, 莫伟彬. 黄酮对运动大鼠脂肪代谢酶与ERRα表达的影响[J]. 广西师范大学学报（自然科学版）, 2016, 34(1): 168-173.
[4] 张杰, 刘倩英, 孙师, 梁任山, 宋德贵. EGCG棕榈酸酯体外抗HCV作用的研究[J]. 广西师范大学学报（自然科学版）, 2015, 33(1): 122-126.
[5] 郭敏, 廖月葵, 徐灵莺, 冼俞均, 何报作. 枸骨与小果十大功劳的叶形态-脉序鉴别特征[J]. 广西师范大学学报（自然科学版）, 2013, 31(1): 97-103.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 李贤江, 石淑芹, 蔡为民, 曹玉青. 基于CA-Markov模型的天津滨海新区土地利用变化模拟[J]. 广西师范大学学报（自然科学版）, 2018, 36(3): 133 -143 .
[2] 温玉卓, 唐胜达, 邓国和. 随机环境下具有阈值分红策略的风险过程的破产时间分析[J]. 广西师范大学学报（自然科学版）, 2018, 36(3): 56 -62 .
[3] 俞春强, 邓方舟, 张显全, 唐振军, 陈艳, 何南. 一种基于多预测值分类的可逆信息隐藏算法[J]. 广西师范大学学报（自然科学版）, 2018, 36(2): 24 -32 .
[4] 贺冬冬, 李传起. 一种改进的基于FFT/IFFT预留子载波的PAPR抑制算法[J]. 广西师范大学学报（自然科学版）, 2014, 32(3): 6 -11 .
[5] 陈美娟, 李传起, 罗德俊, 陆叶. 单个LPFG实现溶液温度和折射率测量的两种方法[J]. 广西师范大学学报（自然科学版）, 2014, 32(4): 1 -5 .
[6] 许固镇, 邓培民. 相伴模糊变换半群的一些性质[J]. 广西师范大学学报（自然科学版）, 2011, 29(2): 26 -30 .
[7] 邱建华, 张延武, 张亚涛, 张浩勤, 刘金盾. 表面化学法改性醋酸纤维素微滤膜[J]. 广西师范大学学报（自然科学版）, 2011, 29(2): 65 -70 .
[8] 吕虹, 秦永彬, 罗聪. 基于Memetic算法的飞机地面作业调度问题研究[J]. 广西师范大学学报（自然科学版）, 2011, 29(2): 145 -150 .
[9] 钟成华, 张文东, 刘鹏, 陈建. 包埋固定化复合菌低温下处理养猪废水研究[J]. 广西师范大学学报（自然科学版）, 2011, 29(3): 52 -56 .
[10] 辜澜涛, 张光琦, 宋德贵. 混合菌发酵豆渣检测其粗蛋白变化情况[J]. 广西师范大学学报（自然科学版）, 2011, 29(3): 80 -83 .
版权所有 © 广西师范大学学报（自然科学版）编辑部
地址：广西桂林市三里店育才路15号　邮编：541004
电话：0773-5857325　E-mail: gxsdzkb@mailbox.gxnu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发