The active ingredients and mechanism of Zuoqing San in the treatment of sigmoid ulcerative colitis by retention enema

Ming Li; Heng Deng; Shuqing Xu; Xiaoli Fang; Kun Tang; Li Chen; Ansheng Zha

doi:10.1515/jcim-2024-0435

Article

The active ingredients and mechanism of Zuoqing San in the treatment of sigmoid ulcerative colitis by retention enema

Ming Li , Heng Deng , Shuqing Xu , Xiaoli Fang , Kun Tang , Li Chen and Ansheng Zha

Published/Copyright: February 24, 2025

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From the journal Journal of Complementary and Integrative Medicine Volume 22 Issue 2

Abstract

Objectives

This investigation aimed to evaluate the efficacy, key active ingredients, and mechanisms of Zuoqing San (ZQS), a traditional Chinese medicine formula, in managing sigmoid ulcerative colitis (SUC).

Methods

A cohort of 126 participants was recruited and treated with ZQS at a daily dosage of 100 mL for 12 weeks. The primary endpoint was the percentage of subjects achieving favorable treatment outcomes. Liquid chromatography-mass spectrometry was employed to identify the principal ingredients of ZQS. Network pharmacology was utilized to predict the central targets of its active ingredients. Protein-protein interaction networks, Gene Ontology enrichment analyses, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for identified core targets. Finally, molecular dynamics simulations of key active ingredients and core targets were performed.

Results

Following 12 weeks of therapy, with a withdrawal rate of 7.93 %, favorable treatment outcomes were observed in 31.03 % of subjects at 4 weeks, 66.37 % at 8 weeks (Odds Ratio: 1.54, 95 % Confidence Interval: 0.41–1.83), and 68.10 % at 12 weeks (Odds Ratio: 1.86, 95 % CI: 0.32–1.27). ZQS comprises 31 principal chemical constituents. Key targets within the protein-protein interaction network included TNF, AKT1, IL6, IL1β, PTGS2, TP53, JUN, MMP9, CASP3, HIF1A, and BCL1. Pathway analysis indicated ZQS primarily impacts the TNF, NF-kB, and IL-17 signaling pathways. Molecular dynamics simulation results showed oxymatrine, cynarin had higher affinity with TNF and IL1β, respectively.

Conclusions

This research elucidates the active components of ZQS and its potential multicomponent–multitarget–multipathway pharmacological mechanisms, demonstrating promising therapeutic potential for SUC management.

Keywords: Zuoqing San; ulcerative colitis; retention enema; active ingredients

Corresponding authors: Heng Deng, Department of Anorectal Surgery, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China, E-mail: dengheng23@outlook.com; and Ansheng Zha, Gastroenterology Department, The First Affiliated Hospital of Anhui University of Chinese Medicine, No. 117, Meishan Road, Hefei City, Hefei, China, E-mail: liming1330551@163.com

Funding source: Anhui Province clinical medical research transformation project

Award Identifier / Grant number: 202427b10020009

Funding source: Xinglin talent training program

Award Identifier / Grant number: 0500-48-30

Research ethics: The local Institutional Review Board (The Ethics committee of Anhui Provincial Hospital of TCM, approval No. 2024AH-97-1) approved this study.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: Ming Li performed this study, and was a major contributor in writing the manuscript. Heng Deng and Ansheng Zha designed this study. Shuqing Xu analyzed and interpreted the patient data. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: Authors state no conflict of interest.
Research funding: Anhui Province clinical medical research transformation project (No. 202427b10020009); and Xinglin talent training program (No. 0500-48-30).
Data availability: Not applicable.

References

1. Wang, YJ, Li, QM, Zha, XQ, Luo, JP. Intervention and potential mechanism of non-starch polysaccharides from natural resources on ulcerative colitis: a review. Int J Biol Macromol 2022;210:545–64. https://doi.org/10.1016/j.ijbiomac.2022.04.208.Search in Google Scholar PubMed

2. Wang, J, Zhang, Q, Deng, Y, Deng, G, Huang, F, Zhou, Y, et al.. Efficacy and safety of heat-sensitive moxibustion in the treatment of ulcerative colitis: a protocol for a systematic review and meta-analysis. Medicine 2021;100:e24078. https://doi.org/10.1097/MD.0000000000024078.Search in Google Scholar PubMed PubMed Central

3. Lu, Q, Xie, Y, Luo, J, Gong, Q, Li, C. Natural flavones from edible and medicinal plants exhibit enormous potential to treat ulcerative colitis. Front Pharmacol 2023;14:1168990. https://doi.org/10.3389/fphar.2023.1168990.Search in Google Scholar PubMed PubMed Central

4. Gros, B, Kaplan, GG. Ulcerative colitis in adults: a review. JAMA 2023;330:951–65. https://doi.org/10.1001/jama.2023.15389.Search in Google Scholar PubMed

5. Xu, L, He, B, Sun, Y, Li, J, Shen, P, Hu, L, et al.. Incidence of inflammatory bowel disease in urban China: a nationwide population-based study. Clin Gastroenterol Hepatol 2023;21:3379–86 e29. https://doi.org/10.1016/j.cgh.2023.08.013.Search in Google Scholar PubMed

6. Li, W, Zhao, T, Wu, D, Li, J, Wang, M, Sun, Y, et al.. Colorectal cancer in ulcerative colitis: mechanisms, surveillance and chemoprevention. Curr Oncol 2022;29:6091–114. https://doi.org/10.3390/curroncol29090479.Search in Google Scholar PubMed PubMed Central

7. Loew, BJ, Siegel, CA. Foam preparations for the treatment of ulcerative colitis. Curr Drug Deliv 2012;9:338–44. https://doi.org/10.2174/156720112801323062.Search in Google Scholar PubMed

8. Duan, ZL, Wang, YJ, Lu, ZH, Tian, L, Xia, ZQ, Wang, KL, et al.. Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: network pharmacology analysis and experimental evidence. Phytomed Int J Phytother Phytopharm 2023;111:154658. https://doi.org/10.1016/j.phymed.2023.154658.Search in Google Scholar PubMed

9. Chen, J, Shen, B, Jiang, Z. Traditional Chinese medicine prescription Shenling BaiZhu powder to treat ulcerative colitis: clinical evidence and potential mechanisms. Front Pharmacol 2022;13:978558. https://doi.org/10.3389/fphar.2022.978558.Search in Google Scholar PubMed PubMed Central

10. Liu, B, Piao, X, Niu, W, Zhang, Q, Ma, C, Wu, T, et al.. Kuijieyuan decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4-dependent PI3K/AKT/NF-kappaB oxidative and inflammatory signaling and gut microbiota. Front Pharmacol 2020;11:1036. https://doi.org/10.3389/fphar.2020.01036.Search in Google Scholar PubMed PubMed Central

11. Lu, L, Shi, JH, Zhang, D, Ma, LJ, Zhang, L, Hou, FG, et al.. [Main characteristics and practical discussions of national drug standards for 196 kinds of Chinese medicine formula granules]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China J Chin Mater Med 2022;47:4536–44. https://doi.org/10.19540/j.cnki.cjcmm.20220414.301.Search in Google Scholar PubMed

12. Vandenbroucke, JP, von Elm, E, Altman, DG, Gotzsche, PC, Mulrow, CD, Pocock, SJ, et al.. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. Ann Intern Med 2007;147:W163–94. https://doi.org/10.7326/0003-4819-147-8-200710160-00010-w1.Search in Google Scholar PubMed

13. Liu, Y, Li, X, Chen, C, Ding, N, Zheng, P, Chen, X, et al.. TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine. Chin Med 2024;19:50. https://doi.org/10.1186/s13020-024-00924-y.Search in Google Scholar PubMed PubMed Central

14. Szklarczyk, D, Kirsch, R, Koutrouli, M, Nastou, K, Mehryary, F, Hachilif, R, et al.. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023;51:D638–46. https://doi.org/10.1093/nar/gkac1000.Search in Google Scholar PubMed PubMed Central

15. Zhou, Y, Zhou, B, Pache, L, Chang, M, Khodabakhshi, AH, Tanaseichuk, O, et al.. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10:1523. https://doi.org/10.1038/s41467-019-09234-6.Search in Google Scholar PubMed PubMed Central

16. Vieira, IHP, Botelho, EB, de Souza Gomes, TJ, Kist, R, Caceres, RA, Zanchi, FB. Visual dynamics: a WEB application for molecular dynamics simulation using GROMACS. BMC Bioinf 2023;24:107. https://doi.org/10.1186/s12859-023-05234-y.Search in Google Scholar PubMed PubMed Central

17. Peng, JF, Wang, W, Peng, JS, Zhao, H. [Meta-analysis of therapeutic effect of retention enema with traditional Chinese medicine on ulcerative colitis]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China J Chin Mater Med 2019;44:4263–71. https://doi.org/10.19540/j.cnki.cjcmm.20190827.501.Search in Google Scholar PubMed

18. D’Inca, R, Paccagnella, M, Cardin, R, Pathak, S, Baldo, V, Giron, MC, et al.. 5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis. World J Gastroenterol 2013;19:5665–70. https://doi.org/10.3748/wjg.v19.i34.5665.Search in Google Scholar PubMed PubMed Central

19. Mao, N, Yu, Y, He, J, Yang, Y, Liu, Z, Lu, Y, et al.. Matrine ameliorates DSS-induced colitis by suppressing inflammation, modulating oxidative stress and remodeling the gut microbiota. Int J Mol Sci 2024;25:6613. https://doi.org/10.3390/ijms25126613.Search in Google Scholar PubMed PubMed Central

20. Liu, C, Wang, R, Jiao, X, Zhang, J, Zhang, C, Wang, Z. Oxysophocarpine suppresses TRAF6 level to ameliorate oxidative stress and inflammatory factors secretion in mice with dextran sulphate sodium (DSS) induced-ulcerative colitis. Microb Pathog 2023;182:106244. https://doi.org/10.1016/j.micpath.2023.106244.Search in Google Scholar PubMed

21. Sun, J, Wang, S, Zhao, Z, Lu, J, Zhang, Y, An, W, et al.. Oxymatrine attenuates ulcerative colitis through inhibiting pyroptosis mediated by the NLRP3 inflammasome. Molecules 2024;29:2897. https://doi.org/10.3390/molecules29122897.Search in Google Scholar PubMed PubMed Central

22. Su, S, Wang, X, Xi, X, Zhu, L, Chen, Q, Zhang, H, et al.. Phellodendrine promotes autophagy by regulating the AMPK/mTOR pathway and treats ulcerative colitis. J Cell Mol Med 2021;25:5707–20. https://doi.org/10.1111/jcmm.16587.Search in Google Scholar PubMed PubMed Central

23. Sun, Y, Zhang, H, Wu, Z, Yu, X, Yin, Y, Qian, S, et al.. Quercitrin rapidly alleviated depression-like behaviors in lipopolysaccharide-treated mice: the involvement of PI3K/AKT/NF-kappaB signaling suppression and CREB/BDNF signaling restoration in the Hippocampus. ACS Chem Neurosci 2021;12:3387–96. https://doi.org/10.1021/acschemneuro.1c00371.Search in Google Scholar PubMed

24. Mehta, R, Bhandari, R, Kuhad, A. Effects of catechin on a rodent model of autism spectrum disorder: implications for the role of nitric oxide in neuroinflammatory pathway. Psychopharmacology 2021;238:3249–71. https://doi.org/10.1007/s00213-021-05941-5.Search in Google Scholar PubMed

25. Chen, S, Tang, S, Zhang, C, Li, Y. Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-kappaB pathway. Immunopharmacol Immunotoxicol 2024;46:107–16. https://doi.org/10.1080/08923973.2023.2281281.Search in Google Scholar PubMed

26. Wang, X, Wang, Y, Yuan, T, Wang, H, Zeng, Z, Tian, L, et al.. Network pharmacology provides new insights into the mechanism of traditional Chinese medicine and natural products used to treat pulmonary hypertension. Phytomed Int J Phytother Phytopharm 2024;135:156062. https://doi.org/10.1016/j.phymed.2024.156062.Search in Google Scholar PubMed

27. Wang, ZY, Li, MZ, Li, WJ, Ouyang, JF, Gou, XJ, Huang, Y. Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology. Phytomed Int J Phytother Phytopharm 2023;108:154538. https://doi.org/10.1016/j.phymed.2022.154538.Search in Google Scholar PubMed

28. Zhang, W, Tian, W, Wang, Y, Jin, X, Guo, H, Wang, Y, et al.. Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer based on network pharmacology and molecular docking. Comput Biol Med 2022;151:106293. https://doi.org/10.1016/j.compbiomed.2022.106293.Search in Google Scholar PubMed

Received: 2024-12-03

Accepted: 2025-02-05

Published Online: 2025-02-24

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Articles in the same Issue

https://doi.org/10.1515/jcim-2024-0435

Keywords for this article

Zuoqing San; ulcerative colitis; retention enema; active ingredients