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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

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

Author(s): Ruilian Xu, Xianyong Liu, Mengfei Tian and Diping Chen*

Volume 23, Issue 8, 2023

Published on: 19 September, 2022

Page: [825 - 833] Pages: 9

DOI: 10.2174/1566524022666220811161111

open access plus

Abstract

Background: Irritable bowel syndrome (IBS) is a known brain-gut disorder. Currently, the molecular and cellular mechanisms of IBS remain unclear. Atractylenolide‐I (ATL-I) is a majorly bioactive component extracted from Rhizoma Atractylodes Macrocephalae.

Methods: Studies have revealed that ATL-I functioned as an anti-tumor drug in various cancers. However, the effects and molecular mechanisms of ATL-I on the pathological processes of colonic mucosal epithelial cells (CMECs) during IBS remain unclear. This study reports ATL-I effectively alleviated the oxidative stress-induced colonic mucosal epithelial cell dysfunction. In colonic mucosal tissues from IBS patients, we detected upregulated miR-34a-5p and suppressed glucose metabolism enzyme expressions. Under H2O2 treatment which mimics in vitro oxidative stress, miR-34a-5p was induced and glucose metabolism was inhibited in the colon mucosal epithelial cell line, NCM460. Meanwhile, ATL-I treatment effectively overcame the oxidative stress-induced miR-34a- 5p expression and glucose metabolism in NCM460 cells.

Result: By bioinformatics analysis, Western blot and luciferase assay, we illustrated that miR-34a-5p directly targeted the 3’UTR region of glucose metabolism key enzyme, lactate dehydrogenase-A (LDHA) in colonic mucosal epithelial cells. Rescue experiments validated that miR-34a-5p inhibited glucose metabolism by targeting LDHA. Finally, we demonstrated that ATL-I treatment reversed the miR-34a-5p-inhibited glucose metabolism and -exacerbated colonic mucosal epithelial cell dysfunction under oxidative stress by modulating the miR-34a-5p-LDHA pathway.

Conclusion: Summarily, our study reports the roles and mechanisms of ATL-I in the oxidative stress-induced colonic mucosal epithelial cell dysfunction during IBS through regulating the miR-34a-5p-LDHA-glucose metabolism axis.

Keywords: Irritable bowel syndrome, atractylenolide‐I, colonic mucosal epithelial cell, miR-34a-5p, glucose metabolism, lactate dehydrogenase-A.

[1]
Ford AC, Sperber AD, Corsetti M, Camilleri M. Irritable bowel syndrome. Lancet 2020; 396(10263): 1675-88.
[http://dx.doi.org/10.1016/S0140-6736(20)31548-8] [PMID: 33049223]
[2]
Defrees DN, Bailey J. Irritable bowel syndrome: Epidemiology, pathophysiology, diagnosis, and treatment. Prim Care 2017; 44(4): 655-71.
[http://dx.doi.org/10.1016/j.pop.2017.07.009] [PMID: 29132527]
[3]
Canakis A, Haroon M, Weber HC. Irritable bowel syndrome and gut microbiota. Curr Opin Endocrinol Diabetes Obes 2020; 27(1): 28-35.
[http://dx.doi.org/10.1097/MED.0000000000000523] [PMID: 31789724]
[4]
Herndon CC, Wang YP, Lu CL. Targeting the gut microbiota for the treatment of irritable bowel syndrome. Kaohsiung J Med Sci 2020; 36(3): 160-70.
[http://dx.doi.org/10.1002/kjm2.12154] [PMID: 31782606]
[5]
Mars RAT, Yang Y, Ward T, et al. Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell 2020; 182(6): 1460-1473.e17.
[http://dx.doi.org/10.1016/j.cell.2020.08.007] [PMID: 32916129]
[6]
Parikh K, Antanaviciute A, Fawkner-Corbett D, et al. Colonic epithelial cell diversity in health and inflammatory bowel disease. Nature 2019; 567(7746): 49-55.
[http://dx.doi.org/10.1038/s41586-019-0992-y] [PMID: 30814735]
[7]
Zhu B, Zhang QL, Hua JW, Cheng WL, Qin LP. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: A review. J Ethnopharmacol 2018; 226: 143-67.
[http://dx.doi.org/10.1016/j.jep.2018.08.023] [PMID: 30130541]
[8]
Qin Y, Yu Y, Yang C, et al. Atractylenolide I inhibits nlrp3 inflammasome activation in colitis-associated colorectal cancer via suppressing Drp1-mediated mitochondrial fission. Front Pharmacol 2021; 12: 674340.
[http://dx.doi.org/10.3389/fphar.2021.674340] [PMID: 34335248]
[9]
Long F, Lin H, Zhang X, Zhang J, Xiao H, Wang T. Atractylenolide-I suppresses tumorigenesis of breast cancer by inhibiting toll-like receptor 4-mediated nuclear factor-κB signaling pathway. Front Pharmacol 2020; 11: 598939.
[http://dx.doi.org/10.3389/fphar.2020.598939] [PMID: 33363472]
[10]
Long F, Wang T, Jia P, et al. Anti-tumor effects of atractylenolide-I on human ovarian cancer cells. Med Sci Monit 2017; 23: 571-9.
[http://dx.doi.org/10.12659/MSM.902886] [PMID: 28141785]
[11]
Zhang JL, Huang WM, Zeng QY. Atractylenolide I protects mice from lipopolysaccharide-induced acute lung injury. Eur J Pharmacol 2015; 765: 94-9.
[http://dx.doi.org/10.1016/j.ejphar.2015.08.022] [PMID: 26297303]
[12]
Hossen MJ, Chou JY, Li SM, et al. An ethanol extract of the rhizome of Atractylodes chinensis exerts anti-gastritis activities and inhibits Akt/NF-κB signaling. J Ethnopharmacol 2019; 228: 18-25.
[http://dx.doi.org/10.1016/j.jep.2018.09.015] [PMID: 30218812]
[13]
Li H, Cao W, Zhang XB, et al. Atractylenolide-1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/c-kit signaling pathway. Mol Med Rep 2021; 24(4): 691.
[http://dx.doi.org/10.3892/mmr.2021.12331] [PMID: 34368880]
[14]
Wang KT, Chen LG, Wu CH, Chang CC, Wang CC. Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol-induced gastric ulcer in vitro and in vivo. J Pharm Pharmacol 2010; 62(3): 381-8.
[http://dx.doi.org/10.1211/jpp.62.03.0014] [PMID: 20487223]
[15]
James JP, Riis LB, Malham M, Høgdall E, Langholz E, Nielsen BS. MicroRNA biomarkers in IBD-differential diagnosis and prediction of colitis-associated cancer. Int J Mol Sci 2020; 21(21): 7893.
[http://dx.doi.org/10.3390/ijms21217893] [PMID: 33114313]
[16]
Wang H. MicroRNAs and apoptosis in colorectal cancer. Int J Mol Sci 2020; 21(15): 5353.
[http://dx.doi.org/10.3390/ijms21155353] [PMID: 32731413]
[17]
Zhang N, Hu X, Du Y, Du J. The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomed Pharmacother 2021; 134: 111099.
[http://dx.doi.org/10.1016/j.biopha.2020.111099] [PMID: 33338745]
[18]
Felli C, Baldassarre A, Masotti A. Intestinal and circulating MicroRNAs in coeliac disease. Int J Mol Sci 2017; 18(9): 1907.
[http://dx.doi.org/10.3390/ijms18091907] [PMID: 28878141]
[19]
Park JH. Dysregulated microRNA expression in irritable bowel syndrome. J Neurogastroenterol Motil 2016; 22(2): 166-7.
[http://dx.doi.org/10.5056/jnm16044] [PMID: 27032543]
[20]
Mahurkar-Joshi S, Chang L. Epigenetic mechanisms in irritable bowel syndrome. Front Psychiatry 2020; 11: 805.
[http://dx.doi.org/10.3389/fpsyt.2020.00805] [PMID: 32922317]
[21]
Song MY, Lim SK, Wang JH, Kim H. The root of Atractylodes macrocephala Koidzumi prevents obesity and glucose intolerance and increases energy metabolism in mice. Int J Mol Sci 2018; 19(1): 278.
[http://dx.doi.org/10.3390/ijms19010278] [PMID: 29342124]
[22]
Tang D, Xu X, Ying J, Xie T, Cao G. Transfer of metastatic traits via miR-200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I. Clin Transl Med 2020; 10(4): e139.
[http://dx.doi.org/10.1002/ctm2.139] [PMID: 32898324]
[23]
Huang CY, Pai YC, Yu LC. Glucose-mediated cytoprotection in the gut epithelium under ischemic and hypoxic stress. Histol Histopathol 2017; 32(6): 543-50.
[http://dx.doi.org/10.14670/HH-11-839] [PMID: 27824216]
[24]
Huang CY, Kuo WT, Huang CY, et al. Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut. J Physiol 2017; 595(2): 505-21.
[http://dx.doi.org/10.1113/JP272208] [PMID: 27121603]
[25]
Xiao X, Huang X, Ye F, et al. The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer. Sci Rep 2016; 6(1): 21735.
[http://dx.doi.org/10.1038/srep21735] [PMID: 26902416]
[26]
Pei LJ, Sun PJ, Ma K, Guo YY, Wang LY, Liu FD. LncRNASNHG7 interferes with miR-34a to de-sensitize gastric cancer cells to cisplatin. Cancer Biomark 2021; 30(1): 127-37.
[http://dx.doi.org/10.3233/CBM-201621] [PMID: 33074217]

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