Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 1: 57 - 65

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.01.006

Atractylenolide I ameliorates post-infectious irritable bowel syndrome by inhibiting the polymerase I and transcript release factor and c-Jun N-terminal kinase/inducible nitric oxide synthase pathway

  • Jianan YUAN ,
  • Kunming CHENG ,
  • Chao LI ,
  • Xiang ZHANG ,
  • Zeyu DING ,
  • Bing LI ,
  • Yongqiu ZHENG
Expand
  • 1 Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Teaching and Research Section of Traditional Chinese Medicine, School of Pharmacy, Wannan Medical College, Wuhu 241000, China
    2 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

Received date: 2023-11-22

  Accepted date: 2024-04-15

  Online published: 2025-01-10

Supported by

The University Collaborative Innovation Project of Anhui: Creation of a Combined Animal Model of Coronary Heart Disease based on the Theory of Xin'an Medicine(GXXT-2020-024);Start-up Funding for Doctoral Research at Wannan Medical College(WYRCQD2018009);Horizontal Project of South Anhui Medical College(H202003)

Fold

Abstract

OBJECTIVE: To explore the therapeutic effect and target of atractylenolide I (AT-I) on post-infectious irritable bowel syndrome (PI-IBS) rats.

METHODS: Therefore, the preliminarily mechanism of AT-I in anti-PI-IBS were first predicted by network pharmacology and molecular docking, then the possible signaling pathways were systematically analyzed. Finally, the potential therapeutic targets and possible signaling pathways of AT-I on PI-IBS in Sprague-Dawley (SD) rat model were verified by experiments.

RESULTS: AT-I could alleviate PI-IBS symptoms and reduce the expression of tumor necrosis factor α, interleukin-6 and Interferon-gamma in PI-IBS SD rat model and inhibit the c-Jun N-terminal kinase/inducible nitric oxide synthase (JNK/iNOS) pathway. Notably, AT-I treatment could inhibit the overexpression of polymerase I and transcript release factor (PTRF).

CONCLUSION: AT-I could alleviate PI-IBS symptoms through downregulation of PTRF and inhibiting the JNK/ iNOS pathway. This study not only provides a scientific basis to clarify the anti-PI-IBS effect of AT-I and its mechanism but also suggests a novel promising therapeutic strategy to treat the PI-IBS.

Key words： atractylenolide Ⅰ; post-infectious irritable bowel syndrome; polymerase Ⅰ and transcript release factor; network pharmacology; MAP kinase signaling system; nitric oxide synthase type Ⅱ

Cite this article

Jianan YUAN , Kunming CHENG , Chao LI , Xiang ZHANG , Zeyu DING , Bing LI , Yongqiu ZHENG . Atractylenolide I ameliorates post-infectious irritable bowel syndrome by inhibiting the polymerase I and transcript release factor and c-Jun N-terminal kinase/inducible nitric oxide synthase pathway[J]. Journal of Traditional Chinese Medicine, 2025 , 45(1) : 57 -65 . DOI: 10.19852/j.cnki.jtcm.2025.01.006

References

1. Sundin J, Rangel I, Repsilber D, Brummer RJ. Cytokine response after stimulation with key commensal bacteria differ in post-infectious irritable bowel syndrome (PI-IBS) patients compared to healthy controls. PLoS One 2015; 10: e0134836.
2. Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med 2017; 376: 2566-78.
3. Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology 2016: S0016-5085(16)00222-5.
4. Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol 2016; 1: 133-46.
5. Berumen A, Edwinson AL, Grover M. Post-infection irritable bowel syndrome. Gastroenterol Clin North Am 2021; 50: 445-61.
6. Black CJ, Ford AC. Global burden of irritable bowel syndrome: Trends, predictions and risk factors. Nat Rev Gastroenterol Hepatol 2020; 17: 473-86.
7. Gong Z, Chen Y, Zhang R, et al. Pharmacokinetics of two alkaloids after oral administration of rhizoma coptidis extract in normal rats and irritable bowel syndrome rats. Evid Based Complement Alternat Med 2014; 2014: 845048.
8. Ghoshal UC. Postinfection irritable bowel syndrome. Gut Liver 2022; 16: 331-40.
9. Camilleri M, Carlson P, BouSaba J, et al. Comparison of biochemical, microbial and mucosal mrna expression in bile acid diarrhoea and irritable bowel syndrome with diarrhoea. Gut 2023; 72: 54-65.
10. Raskov H, Burcharth J, Pommergaard HC, Rosenberg J. Irritable bowel syndrome, the microbiota and the gut-brain axis. Gut microbes 2016; 7: 365-83.
11. Coronel M, Artifon ELA, Lata J, et al. Updated analysis of irritable bowel syndrome: a review of the literature. Rev Gastroenterol Peru 2019; 39: 355-61.
12. Cheng F, Fan Z, Lin C, et al. Effect of altered gut microbiota on visceral hypersensitivity of postinfectious irritable bowel syndrome mice. Eur J Gastroenterol Hepatol 2022; 34: 1220-30.
13. Gracie DJ, Hamlin PJ, Ford AC. The influence of the brain-gut axis in inflammatory bowel disease and possible implications for treatment. Lancet Gastroenterol Hepatol 2019; 4: 632-42.
14. Carco C, Young W, Gearry RB, Talley NJ, McNabb WC, Roy NC. Increasing evidence that irritable bowel syndrome and functional gastrointestinal disorders have a microbial pathogenesis. Front Cell Infect Microbiol 2020; 10: 468.
15. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA 2015; 313: 949-58.
16. Meynier M, Baudu E, Rolhion N, et al. AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms. Gut Microbes 2022; 14: 2022997.
17. Halliez MC, Motta JP, Feener TD, et al. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 2016; 310: G574-85.
18. Chen T, Yin XL, Kang N, et al. Chang'an II decoction ( II )-containing serum ameliorates tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction via MLCK-MLC signaling pathway in rats. Zhong Guo Zhong Xi Yi Jie He Za Zhi 2020; 26: 745-53.
19. Wang FY, Su M, Zheng YQ, et al. Herbal prescription Chang'an Ⅱ repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome. Acta Pharmacol Sin 2015; 36: 708-15.
20. Ruqiao L, Yueli C, Xuelan Z, et al. Rhizoma Atractylodis macrocephalae: a review of photochemistry, pharmacokinetics and pharmacology. Die Pharmazie 2020; 75: 42-55.
21. Liang SB, Han M, Cheng HJ, et al. Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized, multiple-blind, placebo-controlled trial. Trials 2022; 23: 226.
22. Liang SB, Cao HJ, Kong LY, et al. Systematic review and meta-analysis of Chinese herbal formula Tongxie Yaofang for diarrhea-predominant irritable bowel syndrome: evidence for clinical practice and future trials. Front Pharmacol 2022; 13: 904657.
23. Cui XH, Wang HL, Wu R, Yao PA, Wei KZ, Gao JP. Effect of atractylodes macrocephala rhizoma on isoproterenolinduced ventricular remodeling in rats. Mol Med Rep 2018; 17: 2607-13.
24. Xu R, Liu X, Tian M, Chen D. Atractylodes-I overcomes the oxidative stress-induced colonic mucosal epithelial cells dysfunction to prevent irritable bowel syndrome via modulating the miR-34a-5p-LDHA signaling pathway. Curr Mol Med 2023; 23: 825-33.
25. Wu YX, Lu WW, Geng YC, et al. Antioxidant, antimicrobial and anti-inflammatory activities of essential oil derived from the wild rhizome of atractylodes macrocephala. Chem Biodivers 2020; 17: e2000268.
26. Deng M, Chen H, Long J, Song J, Xie L, Li X. Atractylenolides (I, II, and III): a review of their pharmacology and pharmacokinetics. Arch Pharm Res 2021; 44: 633-54.
27. Zhu B, Zhang QL, Hua JW, Cheng WL, Qin LP. The traditional uses, phytochemistry, and pharmacology of atractylodes macro-cephala koidz: a review. J Ethnopharmacol 2018; 226: 143-67.
28. Li X, Rao Z, Xie Z, Qi H, Zeng N. Isolation, structure and bioactivity of polysaccharides from atractylodes macrocephala: a review. J Ethnopharmacol 2022; 296: 115506.
29. Trame MN, Biliouris K, Lesko LJ, Mettetal JT. Systems pharmacology to predict drug safety in drug development. Eur J Pharm Sci 2016; 94: 93-5.
30. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for Traditional Chinese Medicine: review and assessment. Front Pharmacol 2019; 10: 123.
31. Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, Schmidt H. Network pharmacology: curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci 2022; 43: 136-50.
32. Rani I, Kalsi A, Kaur G, et al. Modern drug discovery applications for the identification of novel candidates for COVID-19 infections. Ann Med Surg (Lond) 2022; 80: 104125.
33. Yang C, Chen EA, Zhang Y. Protein-ligand docking in the machine-learning era. Molecules 2022; 27.
34. Langeswaran K, Jeyaraman J, Mariadasse R, Soorangkattan S. Insights from the molecular modeling, docking analysis of illicit drugs and bomb compounds with honey bee odorant binding proteins (obps). Bioinformation 2018; 14: 219-31.
35. Wu YN, Zhou HH, Tian YQ, Yuan JN, Cheng KM, Zheng YQ. Mechanism of paeoniae radix alba-atractylodis macrocephalae rhizoma in Chang' an Ⅱ decoction in the treatment of IBS by network pharmacology and experimental verification. Wan Nan Yi Xue Yuan Xue Bao 2023; 42: 120-6.
36. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 2021; 61: 3891-8.
37. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31: 455-61.
38. Ma X, Wang X, Kang N, et al. The effect of Tong-Xie-Yao-Fang on intestinal mucosal mast cells in postinfectious irritable bowel syndrome rats. Evid Based Complement Alternat Med 2017; 2017: 9086034.
39. Tian YQ, Zhang SP, Zhang KL, et al. Paeoniflorin ameliorates colonic fibrosis in rats with postinfectious irritable bowel syndrome by inhibiting the leptin/leprb pathway. Evid Based Complement Alternat Med 2022; 2022: 6010858.
40. Qin HY, Xiao HT, Wu JC, Berman BM, Sung JJ, Bian ZX. Key factors in developing the trinitrobenzene sulfonic acid-induced post-inflammatory irritable bowel syndrome model in rats. World J Gastroenterol 2012; 18: 2481-92.
41. Isingrini E, Camus V, Le Guisquet AM, Pingaud M, Devers S, Belzung C. Association between repeated unpredictable chronic mild stress (UCMS) procedures with a high fat diet: a model of fluoxetine resistance in mice. PLoS One 2010; 5: e10404.
42. Mineur YS, Belzung C, Crusio WE. Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice. Behav Brain Res 2006; 175: 43-50.
43. Gao H, Zhu X, Xi Y, Li Q, Shen Z, Yang Y. Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress. Exp Ther Med 2018; 15: 1574-9.
44. Tang D, Wang RY, Sun KW, Wu Y, Ding L, Mo Y. Network pharmacology-based prediction of active compounds in the Wenyang Jiedu Huayu formula acting on acute-on-chronic liver failure with experimental support in vitro and in vivo. Front Pharmacol 2022; 13: 1003479.
45. Ribeiro-Carvalho A, Lima CS, Nunes-Freitas AL, Filgueiras CC, Manh?es AC, Abreu-Villa?a Y. Exposure to nicotine and ethanol in adolescent mice: effects on depressive-like behavior during exposure and withdrawal. Behav Brain Res 2011; 221: 282-9.
46. Song AQ, Gao B, Fan JJ, et al. NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice. J Neuroinflammation 2020; 17: 178.
47. Du Z, Ma Z, Lai S, et al. Atractylenolide I ameliorates acetaminophen-induced acute liver injury via the TLR4/MAPKs/NF-kappa B signaling pathways. Front Pharmacol 2022; 13: 797499.
48. Kong D, Mai Z, Chen Y, et al. ATL I, Acts as a SIRT6 activator to alleviate hepatic steatosis in mice via suppression of NLRP3 inflammasome formation. Pharmaceuticals 2022; 15.
49. Chen X, Lu D, Liu W, et al. Therapeutic effect of Atractylenolide I on Aspergillus fumigatus keratitis by affecting MyD88/NF-kappaB pathway and IL-1β, IL-10 expression. Cytokine 2023; 162: 156112.
50. Cryan JF, O'Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev 2019; 99: 1877-2013.
51. Sun X, Zheng Y, Tian Y, et al. Astragalus polysaccharide alleviates alcoholic-induced hepatic fibrosis by inhibiting polymerase I and transcript release factor and the TLR4/JNK/NF-κ B/MyD88 pathway. J Ethnopharmacol 2023; 314: 116662.
52. Bailly C. Atractylenolides, essential components of atractylodes-based traditional herbal medicines: antioxidant, anti-inflammatory and anticancer properties. Eur J Pharmacol 2021; 891: 173735.
53. Yokomori H, Ando W, Yoshimura K, Yamazaki H, Takahashi Y, Oda M. Increases in endothelial caveolin-1 and cavins correlate with cirrhosis progression. Micron 2015; 76: 52-61.
54. Zhou HH, Zhang YM, Zhang SP, et al. Suppression of PTRF alleviates post-infectious irritable bowel syndrome via downregulation of the TLR4 pathway in rats. Front Pharmacol 2021; 12: 724410.
55. Yao CM, Yang XW. Bioactivity-guided isolation of polyacetylenes with inhibitory activity against NO production in LPS-activated RAW264.7 macrophages from the rhizomes of Atractylodes macrocephala. J Ethnopharmacol 2014; 151: 791-9.
56. Wei Y, Fan Y, Huang S, Lyu J, Zhang Y, Hao Z. Baizhu Shaoyao decoction restores the intestinal barrier and brain-gut axis balance to alleviate diarrhea-predominant irritable bowel syndrome via FoxO1/FoxO3a. Phytomedicine 2024; 122: 155163.
57. Xie Z, Lin M, He X, et al. Chemical constitution, pharmacological effects and the underlying mechanism of atractylenolides: a review. Molecules 2023; 28: 3987.
58. Enck P, Aziz Q, Barbara G, et al. Irritable bowel syndrome. Nat Rev Dis Primers 2016; 2: 16014.
59. Zhang Q, Cao YF, Ran RX, et al. Strong specific inhibition of UDP-glucuronosyltransferase 2B7 by Atractylenolide Ⅰ and Ⅲ. Phytother Res 2016; 30: 25-30.
Options
Outlines

/

〈 〉