Exploring the molecular mechanism of Zuojin Pill in treating Helicobacter pylori related ulcers based on bioinformatics and network pharmacology

Abstract

Abstract: Objective To explore the molecular mechanisms and key genes involved in the treatment of Helicobacter pylori (Hp) associated ulcers (PU) with Zuojin Pills using network pharmacology and bioinformatics methods. Methods Screening the active ingredients and targets of Zuojin Wan through the TCMSP database; The gene expression profile microarray data of Hp infected gastric mucosa epithelium were retrieved from GEO database; Homogenize the chip data and analyze differentially expressed microRNAs; Using Starbase to search for significantly differentially expressed microRNA target genes; Extract the intersection of the action target of Zuojin Pill and the key pathogenic genes of Hp related PU; Metascape was used to analyze GO functional analysis of crossing genes; Using GSEA to perform KEGG pathway enrichment analysis on intersecting genes. Results Retrieved 44 active ingredients and 891 action targets of Zuojin pill; 10 significantly differentially expressed microRNAs were screened from the GSE19769 chip; 684 differentially expressed microRNA target genes were found; Obtain specific genes such as BIRC5, HIF1A, and HSP90AB1 by intersecting the two; GO functional analysis involves biological processes such as post-translational protein modification and cell cycle regulation, cell components such as cytoplasm and nucleus, and molecular functions such as protein ligase binding and protein binding; The signaling pathways involved in the treatment of Hp related PU with Zuojin pill include MAPK signaling pathway, WNT signaling pathway, cancer related pathway, etc. Conclusion The results indicate that the treatment of Hp related PU with Zuojin pill mainly plays a role by regulating the MAPK signaling pathway and WNT signaling pathway composed of key genes such as BIRC5, HIF1A, and HSP90AB1.

Key words: Helicobacter pylori, peptic ulcer, Zuojin Pill, network pharmacology, microRNA

CLC Number:

R241

WU Man-ting, WU Jia, QIU Jing-yue, LONG Rong, SONG Hou-pan. Exploring the molecular mechanism of Zuojin Pill in treating Helicobacter pylori related ulcers based on bioinformatics and network pharmacology[J]. ZHONGHUA YANGSHENG BAOJIAN, 2023, 41(24): 64-69.

References

[1] 李军祥,陈誩,肖冰,等.消化性溃疡中西医结合诊疗共识意见(2017年)[J].中国中西医结合消化杂志,2018,26(2):112-120.
[2] 杨艺,孟宪生.消化性溃疡的研究进展[J].世界中医药,2017,12(4):951-955.
[3] 赵文星. 益胃汤联合四联疗法治疗Hp阳性消化性溃疡临床观察[J].光明中医,2019,34(4):617-619.
[4] 杨永强. 中药联合常规四联方案治疗Hp阳性消化性溃疡的效果观察[J].当代医学,2018,24(10):51-53.
[5] 褚璨灿,师为人,陈云志,等.左金丸临床应用与实验研究进展[J].实用中医药杂志,2019,35(5):626-629.
[6] 解静,高杉,李琳,等.网络药理学在中药领域中的研究进展与应用策略[J].中草药,2019,50(10):2257-2265.
[7] GFELLER D, GROSDIDIER A, WIRTH M, et al.Swiss target prediction:a web server for target prediction of bioactive smallmolecules[J].Nucleic Acids Res,2014,42:32-38.
[8] 冯瑶,陈新怡,宋厚盼,等.基于生物信息学的十二指肠腺瘤核心致病基因及其靶向治疗中药活性成分筛选[J].江苏大学学报(医学版),2021,31(2):158-165.
[9] SUBRAMANIAN A, TAMAYO P, MOOTHA V K, et al.Gene set enrichment analysis:a knowledge-based approach for inter-preting genome-wide expression profiles[J].Proc Natl Acad Sci U S A,2005,102(43):15545-15550.
[10] 龚汶,赵宁宁,祁月英.左金丸治疗幽门螺杆菌感染研究进展[J].中医药学报,2022,50(8):101-106.
[11] 尹抗抗,梁媛,李玲,等.左金丸对实验性应激性胃溃疡的保护作用及其机制[J].中国微生态学杂志,2015,27(2):151-155.
[12] 刘晓伟,张红梅,曲宏达,等.左金丸对应激性胃溃疡粘膜损伤保护作用机理的研究[J].江西中医药,2004,35(8):18-20.
[13] 林科名,丁世兰,王强松,等.左金丸总生物碱对束缚水浸应激性胃溃疡模型大鼠神经体液调节的影响[J].中国药理学通报,2013,29(3):401-405.
[14] 李峰,张浩,华桦,等.黄连碱对应激所致小鼠胃黏膜损伤的保护作用[J].华西药学杂志,2007,22(6):713-714.
[15] 杨红莲,段玉红,钱笑音.不同剂量黄连对脾虚大鼠胃黏膜病理形态及CaM/MLCK mRNA表达水平的影响[J].辽宁中医杂志,2017,44(9):1975-1977.
[16] 张云玲. 吴茱萸抗幽门螺杆菌(Helicobacter-pylori)的物质基础研究[D].重庆:重庆理工大学,2014.
[17] JIA B, ZHAO L Y, LIU P P, et al.Limonin ameliorates indomethacin-induced intestinal damage and ulcers through Nrf2/ARE pathway[J].Immun Inflamm Dis,2023,11(2):e787.
[18] WANG L H, CAO H L, LU N, et al.Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells[J].PLoS One,2013,8(2):e56666.
[19] 王哲义. 丹参酮ⅡA磺酸钠调控HIF1α/mTOR介导细胞自噬干预缺血性脑卒中的机制研究[D].北京:北京中医药大学,2021.
[20] MAO L Y, CHEN Q Y, GONG K, et al.Berberine decelerates glucose metabolism via suppression of mTOR-dependent HIF-1α protein synthesis in colon cancer cells[J].Oncol Rep,2018,39(5):2436-2442.
[21] 杨廷荣,孙跃明,雪梅.小檗碱调控HIF-1α和TGF-β抑制鼻咽癌细胞增殖和侵袭转移[J].解剖科学进展,2022,28(5):602-605.
[22] LEE D H, LEE Y J.Quercetin suppresses hypoxia‐induced accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) through inhibiting protein synthesis[J].Journal of cellular biochemistry,2008,105(2):546-553.
[23] BACH A, BENDER-SIGEL J, SCHRENK D, et al.The antioxidant quercetin inhibits cellular proliferation via HIF-1-dependent induction of p21WAF[J].Antioxid Redox Signal,2010,13(4):437-448.
[24] DAI W, GAO Q, QIU J, et al.Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma[J].Tumour Biol,2016,37(5):6307-6313.
[25] LORZADEH S, KOHAN L, GHAVAMI S, et al.Autophagy and the wnt signaling pathway:a focus on wnt/β-catenin signaling[J]. Biochim Biophys Acta Mol Cell Res,2021,1868(3):118926.
[26] 韩亮. 幽门螺杆菌Tipα通过Wnt/β-catenin信号通路上调胃癌干细胞Nanog和Oct4表达[D].衡阳:南华大学,2019.
[27] CHAVA S, BUGIDE S, GUPTA R, et al.Measurement of natural killer cell-mediated cytotoxicity and migration in the context of hepatic tumor cells[J].J Vis Exp,2020,(156):e60714.
[28] 宋厚盼,陈小娟,曾梅艳,等.理中汤调控Raf/MEK/ERK信号通路抗大鼠胃溃疡的效应与机制[J].中国药理学通报,2021,37(8):1291-1298.
[29] 王茜. 黄连素抑制TNF-α刺激ARPE-19细胞分泌炎症因子的作用及机制研究[D].重庆:重庆医科大学,2012.
[30] GONG Y H, JIANG T, LU F Y, et al.Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro:the key role of the MAPK/NF-κB and necroptosis pathways[J].J Pharm Pharmacol,2023,75(5):612-624.
[31] LV J, JI M M, YANG H, et al.Rutaecarpine attenuates high glucose-induced damage in AC16 cardiomyocytes by suppressing the MAPK pathway[J].J Appl Toxicol,2023,43(9):1306-1318.