多机制多靶点综合研究健胃愈疡颗粒对消化性溃疡的治疗作用机制
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简怀玉,柳柳,魏成龙,王子曦,肖满
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1.中南大学湘雅药学院，湖南长沙，400013
2.湖南女子学院，湖南长沙，410000
3.湖南方盛制药股份有限公司，湖南长沙，410221
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摘要：目的：通过网络药理学和分子对接技术，系统研究健胃愈疡颗粒治疗消化性溃疡的作用机制，解析其潜在的活性成分、关键靶点及相关信号通路。方法：在TCMSP数据库中获取健胃愈疡颗粒的化学成分，并结合ADMETlab3.0和SwissADME进行药代动力学筛选。利用SwissTargetPrediction预测靶点，并在GeneCards、DisGeNET及OMIM数据库中筛选消化性溃疡相关靶点，取交集获得核心靶点。使用STRING数据库构建PPI网络，并进行GO富集及KEGG通路分析。此外，采用AutoDockVina进行分子对接，以验证关键成分与核心靶点的结合能力。结果：研究共筛选出197种潜在活性成分和1025个预测靶点，其中209个靶点与消化性溃疡相关。PPI网络分析发现PTGS1、CYP1A2、BDKRB2、CYP2C19和CYP2C9为核心靶点。GO和KEGG分析揭示健胃愈疡颗粒可能通过炎症反应调节、细胞增殖调控及胃泌素信号通路等机制发挥作用。分子对接结果表明，多个关键成分与核心靶点具有良好的结合能力，尤其是6-（3-oxoindolin-2-ylidene）indolo[2，1-b]quinazolin-12-one表现出较强的结合活性。结论：健胃愈疡颗粒可能通过多成分－多靶点－多通路的方式治疗消化性溃疡，为其临床应用及新药开发提供科学依据。
关健词：健胃愈疡颗粒；消化性溃疡；网络药理学；分子对接；蛋白互作网络；信号通路 |
A Comprehensive Multi-Mechanism and Multi-Target Study on the Therapeutic Mechanisms of Jianwei Yuyang Granules in Peptic Ulcer Treatment
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Huaiyu Jian,Liu Liu,Chenglong Wei,Zixi Wang,Man Xiao
1.Xiangya School of Pharmaceutical Sciences，Central South University，Changsha，Hunan 400013，China
2.Hunan Women's University,Changsha,Hunan 410000,China
3.Hunan Fangsheng Pharmaceutical Co.,Ltd. Changsha,Hunan 410221，China
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Abstract：Objective: To systematically investigate the therapeutic mechanisms of Jianwei Yuyang Granules in treating peptic ulcers through network pharmacology and molecular docking techniques,and to elucidate its potential active components,key targets,and related signaling pathways.Methods: The chemical components of Jianwei Yuyang Granules were retrieved from the TCMSP database,followed by pharmacokinetic screening using ADMETlab 3.0 and SwissADME. Targets were predicted via SwissTargetPrediction,and peptic ulcer-related targets were screened from GeneCards,DisGeNET, and OMIM databases. Core targets were identified by intersecting these datasets. A protein-protein interaction（PPI） network was constructed using the STRING database,and GO enrichment and KEGG pathway analyses were performed. Molecular docking with AutoDock Vina was conducted to validate the binding affinity between key components and core targets.Results: A total of 197 potential active components and 1，025 predicted targets were identified,with 209 targets overlapping with peptic ulcer-related genes. PPI network analysis revealed PTGS1,CYP1A2,BDKRB2,CYP2C19,and CYP2C9 as core targets. GO and KEGG analyses suggested that Jianwei Yuyang Granules may exert therapeutic effects by modulating inflammatory responses,regulating cell proliferation,and influencing the gastrin signaling pathway. Molecular docking demonstrated strong binding affinities between multiple key components and core targets,particularly 6-（3-oxoindolin-2-ylidene）indolo[2，1-b]quinazolin-12-one,which exhibited robust binding activity.Conclusion: Jianwei Yuyang Granules likely treats peptic ulcers through a multi-component,multi-target,and multi-pathway mechanism, providing a scientific foundation for its clinical application and novel drug development.
Keywords : Jianwei Yuyang Granules；Peptic Ulcer；Network Pharmacology；Molecular Docking；Protein-Protein Interaction Network；Signaling Pathways
参考文献
[1] Sung J J Y,Kuipers E J,El-Serag H B. Systematic review: the global incidence and prevalence of peptic ulcer disease[J]. Alimentary Pharmacology & Therapeutics,2009,29（9）: 938-946.
[2] Bereda G. Peptic Ulcer disease: definition, pathophy-siology, and treatment [J]. Journal of Biomedical and Biological Sciences,2022,1（2）: 1-10.
[3] Ford A C,Yuan Y,Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis[J]. Gut,2020,69（12）: 2113-2121.
[4] Hooi J K Y,Lai W Y,Ng W K,et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis[J]. Gastroenterology,2017,153（2）: 420-429.
[5] Scally B,Emberson J R,Spata E,et al. Effects of gastroprotectant drugs for the prevention and treatment of NSAID-associated ulcers: a meta-analysis of randomised trials[J]. The Lancet Gastroe-nterology & Hepatology,2018,3（7）: 413-422.
[6] Jung H K,Kang S J,Lee Y C,et al. Evidence-based guidelines for the treatment of Helicobacter pylori infection in Korea 2020[J]. Gut and liver,2021,15（2）: 168.
[7] Savarino V,Marabotto E,Zentilin P,et al. Proton pump inhibitors: use and misuse in the clinical setting[J]. Expert Review of Clinical Pharmacology,2018,11（11）: 1123-113
[8] 朱崇嘉.消化性溃疡中医证的研究进展[J].国医论坛，2014，29（03）:66-68.
[9] 李维.叶柏教授治疗消化性溃疡经验辑要[J].浙江中医药大学学报，2016，40（01）:41-43.
[10] 王培，戴建国，郑亮.健脾益气、活血化瘀法治疗消化性溃疡的中医研究概况[J].中药药理与临床，2015，31（02）:242.
[11] 张毓芹，黄秋月，贾晓芬，等.幽门螺杆菌耐药机制及中医药治疗策略研究进展[J].中医药学报，2025，53（09）:120-125.
[12] 冯好彬.中医药对胃粘膜细胞因子调节作用的研究 进 展 [J]. 白 求 恩 军 医 学 院 学 报 ， 2009 ， 7（03）:175-177.
[13] 黄国栋，黄媛华，黄道富，等.健胃愈疡颗粒治疗慢性胃炎疗效研究[J].中成药，2008，（04）:480-483.
[14] Hopkins A L. Network pharmacology: the next paradigm in drug discovery[J]. Nature Chemical Biology,2008,4（11）: 682-690.
[15] 姚运秀，潘春晖，王晨，等.网络药理学在中药复方的研究进展与应用策略[J].成都大学学报（自然科学版），2020，39（03）:257-263.
[16] Morris G M,Huey R,Lindstrom W,et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility[J]. Journal of Computational Chemistry,2009,30（16）: 2785-2791.
[17] 巴真真，于巍巍.浅谈计算机辅助药物设计在中药研究中的应用[J].实用心脑肺血管病杂志，2012，20（01）:190-191.
[18] 吴可柱，左颖，李爱秀.计算机辅助药物设计在中药作用靶点研究中的应用[J].武警后勤学院学报（医学版），2012，21（06）:479-483.
[19] Zayachkivska O S,Konturek S J,Drozdowicz D,et al. Gastroprotective effects of flavonoids in plant extracts[J]. Journal of Physiology and Pharmacology. Supplement,2005,56（1）: 219-231.
[20] Radziejewska I,Borzym-Kluczyk M,Leszczyńska K. Luteolin alters MUC1 extracellular domain,sT antigen, ADAM-17, IL-8, IL-10 and NF-κB expression in Helicobacter pylori-infected gastric cancer CRL-1739 cells: A preliminary study[J]. Biomedical Reports,2021,14（2）: 19.
[21] Ishiguro M,Takahara M,Takaki A,et al. Berberine Prevents NSAID-Induced Small Intestinal Injury by Protecting Intestinal Barrier and Inhibiting Inflammasome-Associated Activation[J]. Digestive Diseases and Sciences,2025: 1-12.
[22] Chan M V,Wallace J L. Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating physiology to treatments[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2013,305（7）: G467-G473.
[23] Karaca R O,Kalkisim S,Altinbas A,et al. Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR 1 Transporter on Pantoprazole Metabolism and Helicobacter pylori Eradication[J]. Basic & clinical pharmacology & toxicology,2017, 120（2）: 199-206.
[24] Kushwaha V,Agrawal P,Vekaria H,et al. Prostag landins: an overview[J]. European Journal of Pharmaceutical and Medical Research,2024,11（1）: 130-139.
[25] Liu W,Zhang X,Ma T,et al. Uncovering the pharmacological mechanism of Wei-Tong-Xin against gastric ulcer based on network pharmacology combined with in vivo experiment validation[J]. Journal of Ethnopharmacology,2022,293: 115282.
[26] Fourmy D,Gigoux V,Reubi J C. Gastrin in gastroin-testinal diseases[J]. Gastroenterology,2011, 141（3）: 814-818. e3.
[27] Guo Y,Wu Y,Huang T,et al. Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway[J]. Journal of Ethnopharmacology,2024,325: 117739.
[28] Zhou P,Zhou R,Min Y,et al. Network pharmacology and molecular docking analysis on pharmacological mechanisms of Astragalus membranaceus in the treatment of gastric ulcer[J]. Evidence ‐ Based Complementary and Alternative Medicine,2022,2022（1）: 9007396.
[29] Jalil A T,Hassan M M,Ziyad R A,et al. PDE5 inhibitors and gastric mucosa: implications for the management of peptic ulcer disease[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2023, 396（10）: 2261-2267.
[30] Chen J,Zhong H,Huang Z,et al. A critical review of kaempferol in intestinal health and diseases[J]. Antioxidants,2023,12（8）: 1642. |
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