Exploring the Mechanisms of Self-made Kuiyu Pingchang Recipe for the Treatment of Ulcerative Colitis and Irritable Bowel Syndrome using a Network Pharmacology-based Approach and Molecular Docking
- Authors: Wen Y.1, Wang X.2, Si K.2, Xu L.3, Huang S.4, Zhan Y.5
-
Affiliations:
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University
- Gastroenterology Department,, Chengdu First People's Hospital
- Anorectal Department, Luzhou Hospital of Traditional Chinese Medicine
- Gastrointestinal Surgery Department, Chengdu Second People's Hospital
- Gastroenterology Department,, Chengdu First People's Hospital,
- Issue: Vol 20, No 5 (2024)
- Pages: 534-550
- Section: Chemistry
- URL: https://rjeid.com/1573-4099/article/view/644131
- DOI: https://doi.org/10.2174/1573409919666230515103224
- ID: 644131
Cite item
Full Text
Abstract
Background:Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are common intestinal diseases. According to the clinical experience and curative effect, the authors formulated Kuiyu Pingchang Decoction (KYPCD) comprised of Paeoniae radix alba, Aurantii Fructus, Herba euphorbiae humifusae, Lasiosphaera seu Calvatia, Angelicae sinensis radix, Panax ginseng C.A. Mey., Platycodon grandiforus and Allium azureum Ledeb.
Objective:The aim of the present study was to explore the mechanisms of KYPCD in the treatment of UC and IBS following the Traditional Chinese Medicine (TCM) theory of "Treating different diseases with the same treatment".
Methods:The chemical ingredients and targets of KYPCD were obtained using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP). The targets of UC and IBS were extracted using the DisGeNET, GeneCards, DrugBANK, OMIM and TTD databases. The "TCM-component-target" network and the "TCM-shared target-disease" network were imaged using Cytoscape software. The protein-protein interaction (PPI) network was built using the STRING database. The DAVID platform was used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Using Autodock Tools software, the main active components of KYPCD were molecularly docked with their targets and visualized using PyMOL.
Results:A total of 46 active ingredients of KYPCD corresponding to 243 potential targets, 1,565 targets of UC and 1,062 targets of IBS, and 70 targets among active ingredients and two diseases were screened. Core targets in the PPI network included IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA. GO and KEGG enrichment analysis demonstrated 563 biological processes, 48 cellular components, 82 molecular functions and 144 signaling pathways. KEGG enrichment results revealed that the regulated pathways were mainly related to the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways. The results of molecular docking analysis indicated that the core active ingredients of KYPCD had optimal binding activity to their corresponding targets.
Conclusion:KYPCD may use IL6, TNF, AKT1, IL1B, TP53, EGFR and VEGFA as the key targets to achieve the treatment of UC and IBS through the PI3K-AKT, MAPK, HIF-1 and IL-17 pathways.
About the authors
Yong Wen
Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University
Email: info@benthamscience.net
Xiaoxiang Wang
Gastroenterology Department,, Chengdu First People's Hospital
Email: info@benthamscience.net
Ke Si
Gastroenterology Department,, Chengdu First People's Hospital
Email: info@benthamscience.net
Ling Xu
Anorectal Department, Luzhou Hospital of Traditional Chinese Medicine
Email: info@benthamscience.net
Shuoyang Huang
Gastrointestinal Surgery Department, Chengdu Second People's Hospital
Email: info@benthamscience.net
Yu Zhan
Gastroenterology Department,, Chengdu First People's Hospital,
Author for correspondence.
Email: info@benthamscience.net
References
- Segal, J.P.; LeBlanc, J.F.; Hart, A.L. Ulcerative colitis: An update. Clin. Med., 2021, 21(2), 135-139. doi: 10.7861/clinmed.2021-0080 PMID: 33762374
- Ng, S.C.; Tang, W.; Ching, J.Y.; Wong, M.; Chow, C.M.; Hui, A.J.; Wong, T.C.; Leung, V.K.; Tsang, S.W.; Yu, H.H.; Li, M.F.; Ng, K.K.; Kamm, M.A.; Studd, C.; Bell, S.; Leong, R.; de Silva, H.J.; Kasturiratne, A.; Mufeena, M.N.F.; Ling, K.L.; Ooi, C.J.; Tan, P.S.; Ong, D.; Goh, K.L.; Hilmi, I.; Pisespongsa, P.; Manatsathit, S.; Rerknimitr, R.; Aniwan, S.; Wang, Y.F.; Ouyang, Q.; Zeng, Z.; Zhu, Z.; Chen, M.H.; Hu, P.J.; Wu, K.; Wang, X.; Simadibrata, M.; Abdullah, M.; Wu, J.C.; Sung, J.J.Y.; Chan, F.K.L. Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohns and colitis epidemiology study. Gastroenterology, 2013, 145(1), 158-165.e2. doi: 10.1053/j.gastro.2013.04.007 PMID: 23583432
- Hirten, R.P.; Sands, B.E. New therapeutics for ulcerative colitis. Annu. Rev. Med., 2021, 72(1), 199-213. doi: 10.1146/annurev-med-052919-120048 PMID: 33502898
- Ford, A.C.; Sperber, A.D.; Corsetti, M.; Camilleri, M. Irritable bowel syndrome. Lancet, 2020, 396(10263), 1675-1688. doi: 10.1016/S0140-6736(20)31548-8 PMID: 33049223
- Liu, J.; Hou, X. A review of the irritable bowel syndrome investigation on epidemiology, pathogenesis and pathophysiology in China. J. Gastroenterol. Hepatol., 2011, 26(Suppl. 3), 88-93. doi: 10.1111/j.1440-1746.2011.06641.x PMID: 21443718
- Spiller, R.; Major, G. IBS and IBD-separate entities or on a spectrum? Nat. Rev. Gastroenterol. Hepatol., 2016, 13(10), 613-621. doi: 10.1038/nrgastro.2016.141 PMID: 27667579
- Dignass, A.; Eliakim, R.; Magro, F.; Maaser, C.; Chowers, Y.; Geboes, K.; Mantzaris, G.; Reinisch, W.; Colombel, J.F.; Vermeire, S.; Travis, S.; Lindsay, J.O.; Van Assche, G. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis. J. Crohns Colitis, 2012, 6(10), 965-990. doi: 10.1016/j.crohns.2012.09.003 PMID: 23040452
- Zhai, X.; Wang, X.; Wang, L.; Xiu, L.; Wang, W.; Pang, X. Treating different diseases with the same method-a traditional chinese medicine concept analyzed for its biological basis. Front. Pharmacol., 2020, 11, 946. doi: 10.3389/fphar.2020.00946 PMID: 32670064
- Zhang, R.; Yu, S.; Bai, H.; Ning, K. TCM-Mesh: The database and analytical system for network pharmacology analysis for TCM preparations. Sci. Rep., 2017, 7(1), 2821. doi: 10.1038/s41598-017-03039-7 PMID: 28588237
- Zhou, Z.; Chen, B.; Chen, S.; Lin, M.; Chen, Y.; Jin, S.; Chen, W.; Zhang, Y. Applications of network pharmacology in traditional chinese medicine research. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-7. doi: 10.1155/2020/1646905 PMID: 32148533
- Zheng, C.; Pei, T.; Huang, C.; Chen, X.; Bai, Y.; Xue, J.; Wu, Z.; Mu, J.; Li, Y.; Wang, Y. A novel systems pharmacology platform to dissect action mechanisms of traditional Chinese medicines for bovine viral diarrhea disease. Eur. J. Pharm. Sci., 2016, 94, 33-45. doi: 10.1016/j.ejps.2016.05.018 PMID: 27208435
- Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
- Geng, H.; Chen, X.; Wang, C. Systematic elucidation of the pharmacological mechanisms of Rhynchophylline for treating epilepsy via network pharmacology. BMC Complementary Medicine and Therapies, 2021, 21(1), 9. doi: 10.1186/s12906-020-03178-x PMID: 33407404
- Stelzer, G.; Rosen, N.; Plaschkes, I.; Zimmerman, S.; Twik, M.; Fishilevich, S.; Stein, T.I.; Nudel, R.; Lieder, I.; Mazor, Y.; Kaplan, S.; Dahary, D.; Warshawsky, D.; Guan-Golan, Y.; Kohn, A.; Rappaport, N.; Safran, M.; Lancet, D. The GeneCards Suite: From gene data mining to disease genome sequence analyses. In: Curr. Protoc. Bioinformatics, 2016, 54(1), 1-30. doi: 10.1002/cpbi.5
- Amberger, JS; Hamosh, A Searching online mendelian inheritance in man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinformatics., 2017, 58, 1.2.1-1.2.12. doi: 10.1002/cpbi.27
- Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082. doi: 10.1093/nar/gkx1037 PMID: 29126136
- Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839. doi: 10.1093/nar/gkw943 PMID: 27924018
- Yang, H.; Qin, C.; Li, Y.H.; Tao, L.; Zhou, J.; Yu, C.Y.; Xu, F.; Chen, Z.; Zhu, F.; Chen, Y.Z. Therapeutic target database update 2016: Enriched resource for bench to clinical drug target and targeted pathway information. Nucleic Acids Res., 2016, 44(D1), D1069-D1074. doi: 10.1093/nar/gkv1230 PMID: 26578601
- Safran, M.; Dalah, I.; Alexander, J.; Rosen, N.; Iny Stein, T.; Shmoish, M.; Nativ, N.; Bahir, I.; Doniger, T.; Krug, H.; Sirota-Madi, A.; Olender, T.; Golan, Y.; Stelzer, G.; Harel, A.; Lancet, D. GeneCards Version 3: The human gene integrator. Database (Oxford), 2010, 2010, baq020. doi: 10.1093/database/baq020 PMID: 20689021
- Hamosh, A.; Amberger, J.S.; Bocchini, C.; Scott, A.F.; Rasmussen, S.A. Online mendelian inheritance in man (OMIM®): Victor MCKUSICK 's magnum opus. Am. J. Med. Genet. A., 2021, 185(11), 3259-3265. doi: 10.1002/ajmg.a.62407 PMID: 34169650
- Piñero, J.; Saüch, J.; Sanz, F.; Furlong, L.I. The DisGeNET cytoscape app: Exploring and visualizing disease genomics data. Comput. Struct. Biotechnol. J., 2021, 19, 2960-2967. doi: 10.1016/j.csbj.2021.05.015 PMID: 34136095
- Zhou, Y.; Zhang, Y.; Lian, X.; Li, F.; Wang, C.; Zhu, F.; Qiu, Y.; Chen, Y. Therapeutic target database update 2022: facilitating drug discovery with enriched comparative data of targeted agents. Nucleic Acids Res., 2022, 50(D1), D1398-D1407. doi: 10.1093/nar/gkab953 PMID: 34718717
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
- Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C. STRING v11: Proteinprotein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613. doi: 10.1093/nar/gky1131 PMID: 30476243
- Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled proteinprotein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368. doi: 10.1093/nar/gkw937 PMID: 27924014
- Legeay, M.; Doncheva, N.T.; Morris, J.H.; Jensen, L.J. Visualize omics data on networks with Omics Visualizer, a Cytoscape App. F1000 Res., 2020, 9, 157. doi: 10.12688/f1000research.22280.1 PMID: 32399202
- Dedhia, M.; Kohetuk, K.; Crusio, W.E.; Delprato, A. Introducing high school students to the Gene Ontology classification system. F1000 Res., 2019, 8, 241. doi: 10.12688/f1000research.18061.3 PMID: 31431825
- Burenbatu, W.Y.; Wang, Y.; Wang, S.; Narisu; Wuritunashun; Gong, C.; Hashengaowa; Eerdunduleng; Sarula; Guihua; Bai, H. iTRAQ‐based quantitative proteomics analysis of immune thrombocytopenia patients before and after Qishunbaolier treatment. Rapid Commun. Mass Spectrom., 2021, 35(3), e8993. doi: 10.1002/rcm.8993 PMID: 33140498
- Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57. doi: 10.1038/nprot.2008.211 PMID: 19131956
- Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2009, 31(2), 455-461. doi: 10.1002/jcc.21334 PMID: 19499576
- Yuan, S.; Chan, H.C.S.; Filipek, S.; Vogel, H. PyMOL and inkscape bridge the data and the data visualization. Structure, 2016, 24(12), 2041-2042. doi: 10.1016/j.str.2016.11.012 PMID: 27926832
- Viegas, D.J.; Edwards, T.G.; Bloom, D.C.; Abreu, P.A. Virtual screening identified compounds that bind to cyclin dependent kinase 2 and prevent herpes simplex virus type 1 replication and reactivation in neurons. Antiviral Res., 2019, 172, 104621. doi: 10.1016/j.antiviral.2019.104621 PMID: 31634495
- Shen, Z.F.; Wu, H.H.; Zhu, L.; Zhou, Q.; Shen, H. Traditional Chinese medicine for ulcerative colitis: Systematic reviews based on PRIO-harms. Zhongguo Zhongyao Zazhi, 2020, 45(3), 674-682. doi: 10.19540/j.cnki.cjcmm.20190624.501 PMID: 32237528
- Yao, C.J.; Li, Y.L.; Pu, M.J.; Luo, L.H.; Feng, P.M. Traditional Chinese medicine for irritable bowel syndrome. Medicine, 2020, 99(48), e23394. doi: 10.1097/MD.0000000000023394 PMID: 33235116
- Xu, W.; Zhang, Z.; Lu, Y.; Li, M.; Li, J.; Tao, W. Traditional Chinese medicine Tongxie Yaofang treating irritable bowel syndrome with diarrhea and type 2 diabetes mellitus in rats with liver-depression and spleen-deficiency: A preliminary study. Front. Nutr., 2022, 9, 968930. doi: 10.3389/fnut.2022.968930 PMID: 36438735
- Yu, H.; Sun, H.; Wang, K.; Liang, X.; Ding, Y.; Chang, X.; Guo, J.; Peng, D.; Gui, S. Study of the therapeutic effects of Painong powder on ulcerative colitis and the role of Platycodonis Radix in the prescription based on pharmacodynamic, pharmacokinetic, and tissue distribution analyses. J. Ethnopharmacol., 2022, 285, 114872. doi: 10.1016/j.jep.2021.114872 PMID: 34838618
- Zhang, Y.; Liu, R.; Wang, J.; Yan, S.; Guo, Z. To assess the effective and safety of compound glutamine entersoluble capsules in irritable bowel syndrome. Medicine, 2021, 100(10), e25098. doi: 10.1097/MD.0000000000025098 PMID: 33725903
- Shi, L.; Wang, J.; Yang, Q.; Shi, L.; Liu, L.; Feng, X.; Chai, S.; Gou, J.; Zang, F.; He, S. Effect of Yang-activating and stasis-eliminating decoction from Traditional Chinese Medicine on intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium. J. Tradit. Chin. Med., 2017, 37(4), 452-460.
- Zhou, J.X.; Wink, M. Reversal of multidrug resistance in human colon cancer and human leukemia cells by three plant extracts and their major secondary metabolites. Medicines, 2018, 5(4), 123. doi: 10.3390/medicines5040123 PMID: 30428619
- Feng, S.H.; Zhao, B.; Zhan, X.; Motanyane, R.; Wang, S.M.; Li, A. Danggui Buxue Decoction in the treatment of metastatic colon cancer: Network pharmacology analysis and experimental validation. Drug Des. Devel. Ther., 2021, 15, 705-720. doi: 10.2147/DDDT.S293046 PMID: 33658761
- Chen, S.T.; Lee, T.Y.; Tsai, T.H.; Lin, Y.C.; Lin, C.P.; Shieh, H.R.; Hsu, M.L.; Chi, C.W.; Lee, M.C.; Chang, H.H.; Chen, Y.J. The traditional chinese medicine dangguibuxue tang sensitizes colorectal cancer cells to chemoradiotherapy. Molecules, 2016, 21(12), 1677. doi: 10.3390/molecules21121677 PMID: 27929437
- Wargovich, M.J. Colon cancer chemoprevention with ginseng and other botanicals. J. Korean Med. Sci., 2001, 16Suppl(Suppl.), S81-S86. doi: 10.3346/jkms.2001.16.S.S81 PMID: 11748382
- Chen, H.; Li, G.; Liu, Y.; Lang, Y.; Yang, W.; Zhang, W.; Liang, X. Jiegeng decoction potentiates the anticancer efficacy of paclitaxel in vivo and in vitro. Front. Pharmacol., 2022, 13, 827520. doi: 10.3389/fphar.2022.827520 PMID: 35281908
- Liu, Y.T.; Tzang, B.S.; Yow, J.; Chiang, Y.H.; Huang, C.Y.; Hsu, T.C. Traditional Chinese medicine formula T33 inhibits the proliferation of human colorectal cancer cells by inducing autophagy. Environ. Toxicol., 2022, 37(5), 1007-1017. doi: 10.1002/tox.23460 PMID: 34995006
- Luo, X.; Zheng, Y.; Bao, Y.; Wang, S.; Li, T.; Leng, J.; Meng, X. Potential effects of fructus aurantii ethanol extracts against colitis-associated carcinogenesis through coordination of Notch/NF-κB/IL-1 signaling pathways. Biomed. Pharmacother., 2022, 152, 113278. doi: 10.1016/j.biopha.2022.113278 PMID: 35709655
- Zhao, B.; Kang, Q.; Peng, Y.; Xie, Y.; Chen, C.; Li, B.; Wu, Q. Effect of Angelica sinensis root extract on cancer prevention in different stages of an AOM/DSS mouse model. Int. J. Mol. Sci., 2017, 18(8), 1750. doi: 10.3390/ijms18081750 PMID: 28800083
- Park, J.S.; Kim, S.H.; Han, K.M.; Kim, Y.S.; Kwon, E.; Paek, S.H.; Seo, Y.K.; Yun, J.W.; Kang, B.C. Efficacy and safety evaluation of black ginseng (Panax ginseng C.A. Mey.) extract (CJ EnerG): Broad spectrum cytotoxic activity in human cancer cell lines and 28-day repeated oral toxicity study in Sprague-Dawley rats. BMC Complement. Med. Ther., 2022, 22(1), 44. doi: 10.1186/s12906-022-03522-3 PMID: 35172794
- Tanaka, T.; Narazaki, M.; Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol., 2014, 6(10), a016295. doi: 10.1101/cshperspect.a016295 PMID: 25190079
- Tang, Q.Z.; Liu, Y.L. Expression of HBD-2, NF-κB, IL-6 and IL-23 in the colonic mucosa of ulcerative colitis and irritable bowel syndrome. China Modern Doctor., 2013, 51(22), 42-44.
- Morsy, M.A.; Gupta, S.; Nair, A.B.; Venugopala, K.N.; Greish, K.; El-Daly, M. Protective effect of Spirulina platensis extract against dextran-sulfate-sodium-induced ulcerative colitis in rats. Nutrients, 2019, 11(10), 2309. doi: 10.3390/nu11102309 PMID: 31569451
- Gupta, R.A.; Motiwala, M.N.; Mahajan, U.N.; Sabre, S.G. Protective effect of Sesbania grandiflora on acetic acid induced ulcerative colitis in mice by inhibition of TNF-α and IL-6. J. Ethnopharmacol., 2018, 219, 222-232. doi: 10.1016/j.jep.2018.02.043 PMID: 29530609
- Wang, C.; Li, W.; Wang, H.; Ma, Y.; Zhao, X.; Zhang, X.; Yang, H.; Qian, J.; Li, J. Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota. BMC Microbiol., 2019, 19(1), 246. doi: 10.1186/s12866-019-1610-8 PMID: 31694526
- Zhang, Y.; Zhang, Y.; Zhao, Y.; Wu, W.; Meng, W.; Zhou, Y.; Qiu, Y.; Li, C. Protection against ulcerative colitis and colorectal cancer by evodiamine via anti inflammatory effects. Mol. Med. Rep., 2022, 25(5), 188. doi: 10.3892/mmr.2022.12704 PMID: 35362542
- Hu, J.; Huang, H.; Che, Y.; Ding, C.; Zhang, L.; Wang, Y.; Hao, H.; Shen, H.; Cao, L. Qingchang Huashi Formula attenuates DSS-induced colitis in mice by restoring gut microbiota-metabolism homeostasis and goblet cell function. J. Ethnopharmacol., 2021, 266, 113394. doi: 10.1016/j.jep.2020.113394 PMID: 32941971
- Huang, C.; Dong, J.; Jin, X.; Ma, H.; Zhang, D.; Wang, F.; Cheng, L.; Feng, Y.; Xiong, X.; Jiang, J.; Hu, L.; Lei, M.; Wu, B.; Zhang, G. Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice. J. Ethnopharmacol., 2020, 261, 112951. doi: 10.1016/j.jep.2020.112951 PMID: 32574670
- Li, R.; Chen, Y.; Shi, M.; Xu, X.; Zhao, Y.; Wu, X.; Zhang, Y. Gegen Qinlian decoction alleviates experimental colitis via suppressing TLR4/NF-κB signaling and enhancing antioxidant effect. Phytomedicine, 2016, 23(10), 1012-1020. doi: 10.1016/j.phymed.2016.06.010 PMID: 27444346
- Migliorini, P.; Italiani, P.; Pratesi, F.; Puxeddu, I.; Boraschi, D. The IL-1 family cytokines and receptors in autoimmune diseases. Autoimmun. Rev., 2020, 19(9), 102617. doi: 10.1016/j.autrev.2020.102617 PMID: 32663626
- Claesson-Welsh, L.; Welsh, M. VEGFA and tumour angiogenesis. J. Intern. Med., 2013, 273(2), 114-127. doi: 10.1111/joim.12019 PMID: 23216836
- Zhu, F.; Zheng, J.; Xu, F.; Xi, Y.; Chen, J.; Xu, X. Resveratrol alleviates dextran sulfate sodium-induced acute ulcerative colitis in mice by mediating PI3K/Akt/VEGFA pathway. Front. Pharmacol., 2021, 12, 693982. doi: 10.3389/fphar.2021.693982 PMID: 34497510
- Talukdar, S.; Emdad, L.; Das, S.K.; Fisher, P.B. EGFR: An essential receptor tyrosine kinase-regulator of cancer stem cells. Adv. Cancer Res., 2020, 147, 161-188. doi: 10.1016/bs.acr.2020.04.003 PMID: 32593400
- Liu, X.; Fan, Y.; Du, L.; Mei, Z.; Fu, Y. In silico and in vivo studies on the mechanisms of chinese medicine formula (Gegen Qinlian Decoction) in the treatment of ulcerative colitis. Front. Pharmacol., 2021, 12, 665102. doi: 10.3389/fphar.2021.665102 PMID: 34177580
- Synoradzki, K.J.; Bartnik, E.; Czarnecka, A.M.; Fiedorowicz, M.; Firlej, W.; Brodziak, A.; Stasinska, A.; Rutkowski, P.; Grieb, P. TP53 in biology and treatment of osteosarcoma. Cancers, 2021, 13(17), 4284. doi: 10.3390/cancers13174284 PMID: 34503094
- Arai, N.; Kudo, T.; Tokita, K.; Kyodo, R.; Sato, M.; Miyata, E.; Hosoi, K.; Ikuse, T.; Jimbo, K.; Ohtsuka, Y.; Shimizu, T. Expression of oncogenic molecules in pediatric ulcerative colitis. Digestion, 2022, 103(2), 150-158. doi: 10.1159/000519559 PMID: 34718239
- Liu, J.; Liu, J.; Tong, X.; Peng, W.; Wei, S.; Sun, T.; Wang, Y.; Zhang, B.; Li, W. Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of huai hua san against ulcerative colitis. Drug Des. Devel. Ther., 2021, 15, 3255-3276. doi: 10.2147/DDDT.S319786 PMID: 34349502
- Wang, M.; Li, J.; Yin, Y.; Liu, L.; Wang, Y.; Qu, Y.; Hong, Y.; Ji, S.; Zhang, T.; Wang, N.; Liu, J.; Cao, X.; Zao, X.; Zhang, S. Network pharmacology and in vivo experiment-based strategy to investigate mechanisms of JingFangFuZiLiZhong formula for ulcerative colitis. Ann. Med., 2022, 54(1), 3218-3232. doi: 10.1080/07853890.2022.2095665 PMID: 36382627
- Yang, Y.; Hua, Y.; Chen, W.; Zheng, H.; Wu, H.; Qin, S.; Huang, S. Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis. Front. Pharmacol., 2022, 13, 1037856. doi: 10.3389/fphar.2022.1037856 PMID: 36532769
- Sarker, R.S.J.; Steiger, K. A critical role for Akt1 signaling in acute pancreatitis progression . J. Pathol., 2020, 251(1), 1-3. doi: 10.1002/path.5391 PMID: 32003469
- Zhu, Y.; Shi, Y.; Ke, X.; Xuan, L.; Ma, Z. RNF8 induces autophagy and reduces inflammation by promoting AKT degradation via ubiquitination in ulcerative colitis mice. J. Biochem., 2020, 168(5), 445-453. doi: 10.1093/jb/mvaa068 PMID: 32597970
- Cui, X.F.; Zhou, W.M.; Yang, Y.; Zhou, J.; Li, X.L.; Lin, L.; Zhang, H.J. Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome. World J. Gastroenterol., 2014, 20(37), 13521-13529. doi: 10.3748/wjg.v20.i37.13521 PMID: 25309082
- Compare, D.; Rocco, A.; Coccoli, P.; Angrisani, D.; Sgamato, C.; Iovine, B.; Salvatore, U.; Nardone, G. Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response: An ex-vivo organ culture model of post-infectious irritable bowel syndrome. BMC Gastroenterol., 2017, 17(1), 53. doi: 10.1186/s12876-017-0605-x PMID: 28410580
- Seyedmirzaee, S.; Hayatbakhsh, M.M.; Ahmadi, B.; Baniasadi, N.; Bagheri Rafsanjani, A.M.; Nikpoor, A.R.; Mohammadi, M. Serum immune biomarkers in irritable bowel syndrome. Clin. Res. Hepatol. Gastroenterol., 2016, 40(5), 631-637. doi: 10.1016/j.clinre.2015.12.013 PMID: 26850360
- Kuo, B.; Bhasin, M.; Jacquart, J.; Scult, M.A.; Slipp, L.; Riklin, E.I.K.; Lepoutre, V.; Comosa, N.; Norton, B.A.; Dassatti, A.; Rosenblum, J.; Thurler, A.H.; Surjanhata, B.C.; Hasheminejad, N.N.; Kagan, L.; Slawsby, E.; Rao, S.R.; Macklin, E.A.; Fricchione, G.L.; Benson, H.; Libermann, T.A.; Korzenik, J.; Denninger, J.W. Genomic and clinical effects associated with a relaxation response mind-body intervention in patients with irritable bowel syndrome and inflammatory bowel disease. PLoS One, 2015, 10(4), e0123861. doi: 10.1371/journal.pone.0123861 PMID: 25927528
- Sun, M.H.; Sun, L.Q.; Guo, G.L.; Zhang, S. Tumour necrosis factor-α gene -308 G > A and -238 G > A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children. J. Clin. Pharm. Ther., 2019, 44(2), 180-187. doi: 10.1111/jcpt.12775 PMID: 30578560
- Zeng, L.; Li, K.; Wei, H.; Hu, J.; Jiao, L.; Yu, S.; Xiong, Y. A novel EphA2 inhibitor exerts beneficial effects in PI-IBS in vivo and in vitro models via Nrf2 and NF-κB signaling pathways. Front. Pharmacol., 2018, 9, 272. doi: 10.3389/fphar.2018.00272 PMID: 29662452
- Wang, F.; Su, M.; Zheng, Y.; Wang, X.; Kang, N.; Chen, T.; Zhu, E.; Bian, Z.; Tang, X. Herbal prescription Changan II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome. Acta Pharmacol. Sin., 2015, 36(6), 708-715. doi: 10.1038/aps.2014.170 PMID: 25960135
- Wang, Y.; Cui, W.; Yang, C.; Wei, H.; Liu, Q.; Xiong, L.; Li, H.; Lin, Y. Comparison of Geqingpi and Sihuaqingpi based on ultra‐high‐performance liquid chromatography‐tandem mass spectrometry combined with multivariate statistics, network pharmacology analysis, and molecular docking. J. Sep. Sci., 2022, 45(22), 4079-4098. doi: 10.1002/jssc.202200564 PMID: 36200604
- Sun, Y.; Liu, W.Z.; Liu, T.; Feng, X.; Yang, N.; Zhou, H.F. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J. Recept. Signal Transduct. Res., 2015, 35(6), 600-604. doi: 10.3109/10799893.2015.1030412 PMID: 26096166
- Guo, Y.J.; Pan, W.W.; Liu, S.B.; Shen, Z.F.; Xu, Y.; Hu, L.L. ERK/MAPK signalling pathway and tumorigenesis (Review). Exp. Ther. Med., 2020, 19(3), 1997-2007. doi: 10.3892/etm.2020.8454 PMID: 32104259
- Kim, E.K.; Choi, E.J. Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta Mol. Basis Dis., 2010, 1802(4), 396-405. doi: 10.1016/j.bbadis.2009.12.009 PMID: 20079433
- Yong, H.Y.; Koh, M.S.; Moon, A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin. Investig. Drugs, 2009, 18(12), 1893-1905. doi: 10.1517/13543780903321490 PMID: 19852565
- Zheng, Y.; Han, Z.; Zhao, H.; Luo, Y. MAPK: A key player in the development and progression of stroke. CNS Neurol. Disord. Drug Targets, 2020, 19(4), 248-256. doi: 10.2174/1871527319666200613223018 PMID: 32533818
- Bora, G.; Yaba, A. The role of mitogen‐activated protein kinase signaling pathway in endometriosis. J. Obstet. Gynaecol. Res., 2021, 47(5), 1610-1623. doi: 10.1111/jog.14710 PMID: 33590617
- Yu, L.; Wei, J.; Liu, P. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin. Cancer Biol., 2022, 85, 69-94. doi: 10.1016/j.semcancer.2021.06.019 PMID: 34175443
- Xu, F.; Na, L.; Li, Y.; Chen, L. RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci., 2020, 10(1), 54. doi: 10.1186/s13578-020-00416-0 PMID: 32266056
- Huang, X.; Liu, G.; Guo, J.; Su, Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci., 2018, 14(11), 1483-1496. doi: 10.7150/ijbs.27173 PMID: 30263000
- Basile, M.S.; Cavalli, E.; McCubrey, J.; Hernández-Bello, J.; Muñoz-Valle, J.F.; Fagone, P.; Nicoletti, F. The PI3K/Akt/mTOR pathway: A potential pharmacological target in COVID-19. Drug Discov. Today, 2022, 27(3), 848-856. doi: 10.1016/j.drudis.2021.11.002 PMID: 34763066
- Wang, M.; Zhang, J.; Gong, N. Role of the PI3K/Akt signaling pathway in liver ischemia reperfusion injury: A narrative review. Ann. Palliat. Med., 2022, 11(2), 806-817. doi: 10.21037/apm-21-3286 PMID: 35016518
- Wang, J.; Hu, K.; Cai, X.; Yang, B.; He, Q.; Wang, J.; Weng, Q. Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm. Sin. B, 2022, 12(1), 18-32. doi: 10.1016/j.apsb.2021.07.023 PMID: 35127370
- Qin, W.; Cao, L.; Massey, I.Y. Role of PI3K/Akt signaling pathway in cardiac fibrosis. Mol. Cell. Biochem., 2021, 476(11), 4045-4059. doi: 10.1007/s11010-021-04219-w PMID: 34244974
- Sun, K.; Luo, J.; Guo, J.; Yao, X.; Jing, X.; Guo, F. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review. Osteoarthr. Cartil., 2020, 28(4), 400-409. doi: 10.1016/j.joca.2020.02.027 PMID: 32081707
- Zhang, M.; Zhang, X. The role of PI3K/AKT/FOXO signaling in psoriasis. Arch. Dermatol. Res., 2019, 311(2), 83-91. doi: 10.1007/s00403-018-1879-8 PMID: 30483877
- Pezzuto, A.; Carico, E. Role of HIF-1 in Cancer progression: Novel insights. A review. Curr. Mol. Med., 2019, 18(6), 343-351. doi: 10.2174/1566524018666181109121849 PMID: 30411685
- Korbecki, J.; Simińska, D.; Gąssowska-Dobrowolska, M.; Listos, J.; Gutowska, I.; Chlubek, D.; Baranowska-Bosiacka, I. Chronic and cycling hypoxia: Drivers of cancer chronic inflammation through HIF-1 and NF-κB activation: A review of the molecular mechanisms. Int. J. Mol. Sci., 2021, 22(19), 10701. doi: 10.3390/ijms221910701 PMID: 34639040
- Semenza, G.L. Hypoxia-inducible factor 1 and cardiovascular disease. Annu. Rev. Physiol., 2014, 76(1), 39-56. doi: 10.1146/annurev-physiol-021113-170322 PMID: 23988176
- Ghoreschi, K.; Balato, A.; Enerbäck, C.; Sabat, R. Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet, 2021, 397(10275), 754-766. doi: 10.1016/S0140-6736(21)00184-7 PMID: 33515492
- Fletcher, J.M.; Moran, B.; Petrasca, A.; Smith, C.M. IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. Clin. Exp. Immunol., 2020, 201(2), 121-134. doi: 10.1111/cei.13449 PMID: 32379344
- Bridgewood, C.; Newton, D.; Bragazzi, N.; Wittmann, M.; McGonagle, D. Unexpected connections of the IL-23/IL-17 and IL-4/IL-13 cytokine axes in inflammatory arthritis and enthesitis. Semin. Immunol., 2021, 58, 101520. doi: 10.1016/j.smim.2021.101520 PMID: 34799224
- Dong, L.; Du, H.; Zhang, M.; Xu, H.; Pu, X.; Chen, Q.; Luo, R.; Hu, Y.; Wang, Y.; Tu, H.; Zhang, J.; Gao, F. Anti‐inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/MTOR signaling pathway and regulating gut microbiota. Phytother. Res., 2022, 36(5), 2081-2094. doi: 10.1002/ptr.7429 PMID: 35229916
- Ni, L.; Lu, Q.; Tang, M.; Tao, L.; Zhao, H.; Zhang, C.; Yu, Y.; Wu, X.; Liu, H.; Cui, R. Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways. Inflammopharmacology, 2022, 30(3), 907-918. doi: 10.1007/s10787-022-00955-7 PMID: 35303235
- Zaghloul, M.S.; Elshal, M.; Abdelmageed, M.E. Preventive empagliflozin activity on acute acetic acid-induced ulcerative colitis in rats via modulation of SIRT-1/PI3K/AKT pathway and improving colon barrier. Environ. Toxicol. Pharmacol., 2022, 91, 103833. doi: 10.1016/j.etap.2022.103833 PMID: 35218923
- Lin, X.; Guo, X.; Qu, L.; Tu, J.; Li, S.; Cao, G.; Liu, Y. Preventive effect of Atractylodis Rhizoma extract on DSS-induced acute ulcerative colitis through the regulation of the MAPK/NF-κB signals in vivo and in vitro. J. Ethnopharmacol., 2022, 292, 115211. doi: 10.1016/j.jep.2022.115211 PMID: 35331877
- Ma, H.; Zhou, M.; Duan, W.; Chen, L.; Wang, L.; Liu, P. Anemoside B4 prevents acute ulcerative colitis through inhibiting of TLR4/NF-κB/MAPK signaling pathway. Int. Immunopharmacol., 2020, 87, 106794. doi: 10.1016/j.intimp.2020.106794 PMID: 32688280
- Deng, X.; Wang, Y.; Tian, L.; Yang, M.; He, S.; Liu, Y.; Khan, A.; Li, Y.; Cao, J.; Cheng, G. Anneslea fragrans Wall. ameliorates ulcerative colitis via inhibiting NF-κB and MAPK activation and mediating intestinal barrier integrity. J. Ethnopharmacol., 2021, 278, 114304. doi: 10.1016/j.jep.2021.114304 PMID: 34116185
- Zhuang, H.; Lv, Q.; Zhong, C.; Cui, Y.; He, L.; Zhang, C.; Yu, J. Tiliroside ameliorates ulcerative colitis by restoring the M1/M2 macrophage balance via the HIF-1α/glycolysis pathway. Front. Immunol., 2021, 12, 649463. doi: 10.3389/fimmu.2021.649463 PMID: 33868286
- Brown, E.; Rowan, C.; Strowitzki, M.J.; Fagundes, R.R.; Faber, K.N.; Güntsch, A.; Halligan, D.N.; Kugler, J.; Jones, F.; Lee, C.T.; Doherty, G.; Taylor, C.T. Mucosal inflammation downregulates PHD1 expression promoting a barrier‐protective HIF‐1α response in ulcerative colitis patients. FASEB J., 2020, 34(3), 3732-3742. doi: 10.1096/fj.201902103R PMID: 31944416
- Kakiuchi, N.; Yoshida, K.; Uchino, M.; Kihara, T.; Akaki, K.; Inoue, Y.; Kawada, K.; Nagayama, S.; Yokoyama, A.; Yamamoto, S.; Matsuura, M.; Horimatsu, T.; Hirano, T.; Goto, N.; Takeuchi, Y.; Ochi, Y.; Shiozawa, Y.; Kogure, Y.; Watatani, Y.; Fujii, Y.; Kim, S.K.; Kon, A.; Kataoka, K.; Yoshizato, T.; Nakagawa, M.M.; Yoda, A.; Nanya, Y.; Makishima, H.; Shiraishi, Y.; Chiba, K.; Tanaka, H.; Sanada, M.; Sugihara, E.; Sato, T.; Maruyama, T.; Miyoshi, H.; Taketo, M.M.; Oishi, J.; Inagaki, R.; Ueda, Y.; Okamoto, S.; Okajima, H.; Sakai, Y.; Sakurai, T.; Haga, H.; Hirota, S.; Ikeuchi, H.; Nakase, H.; Marusawa, H.; Chiba, T.; Takeuchi, O.; Miyano, S.; Seno, H.; Ogawa, S. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature, 2020, 577(7789), 260-265. doi: 10.1038/s41586-019-1856-1 PMID: 31853061
- Chen, Y.; Chen, Y.; Cao, P.; Su, W.; Zhan, N.; Dong, W. Fusobacterium nucleatum facilitates ulcerative colitis through activating IL‐17F signaling to NF‐κB via the upregulation of CARD3 expression. J. Pathol., 2020, 250(2), 170-182. doi: 10.1002/path.5358 PMID: 31610014
- Li, B.; Luo, X.F.; Liu, S.W.; Zhao, N.; Li, H.N.; Zhang, W.; Chen, Y.Y.; Bao, A.; Wang, J.G.; Wang, Q.S. Abdominal massage reduces visceral hypersensitivity via regulating GDNF and PI3K/AKT signal pathway in a rat model of irritable bowel syndrome. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-10. doi: 10.1155/2020/3912931 PMID: 32565856
- Fei, L.; Wang, Y. microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB. IUBMB Life, 2020, 72(7), 1468-1480. doi: 10.1002/iub.2270 PMID: 32187820
- Mahurkar-Joshi, S.; Rankin, C.R.; Videlock, E.J.; Soroosh, A.; Verma, A.; Khandadash, A.; Iliopoulos, D.; Pothoulakis, C.; Mayer, E.A.; Chang, L. The colonic mucosal MicroRNAs, MicroRNA-219a-5p, and MicroRNA-338-3p are downregulated in irritable bowel syndrome and are associated with barrier function and MAPK signaling. Gastroenterology, 2021, 160(7), 2409-2422.e19. doi: 10.1053/j.gastro.2021.02.040 PMID: 33617890
- Luo, H.; Vong, C.T.; Tan, D.; Zhang, J.; Yu, H.; Yang, L.; Zhang, C.; Luo, C.; Zhong, Z.; Wang, Y. Panax notoginseng saponins modulate the inflammatory response and improve IBD-like symptoms via TLR/NF-κB and MAPK signaling pathways. Am. J. Chin. Med., 2021, 49(4), 925-939. doi: 10.1142/S0192415X21500440 PMID: 33829964
- Yang, Y.; Qian, C.; Wu, R.; Wang, R.; Ou, J.; Liu, S. Exploring the mechanism of the Fructus Mume and Rhizoma Coptidis herb pair intervention in Ulcerative Colitis from the perspective of inflammation and immunity based on systemic pharmacology. BMC Complement. Med. Ther., 2023, 23(1), 11. doi: 10.1186/s12906-022-03823-7 PMID: 36647064
- Shou, X.; Wang, Y.; Zhang, X.; Zhang, Y.; Yang, Y.; Duan, C.; Yang, Y.; Jia, Q.; Yuan, G.; Shi, J.; Shi, S.; Cui, H.; Hu, Y. Network pharmacology and molecular docking analysis on molecular mechanism of Qingzi Zhitong decoction in the treatment of ulcerative colitis. Front. Pharmacol., 2022, 13, 727608. doi: 10.3389/fphar.2022.727608 PMID: 35237152
- Tang, R.; Peng, X.; Zhou, X.; Zheng, Z.; Yin, J.; Liu, H. Mechanism of the treatment of irritable bowel syndrome with sini powder and Tong Xie Yao Fang decoction based on network pharmacology. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-13. doi: 10.1155/2022/3598856 PMID: 35399629
Supplementary files
