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

Ruilian      Xu; Xianyong      Liu; Mengfei      Tian; Diping      Chen

doi:10.2174/1566524022666220811161111

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

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DOI https://dx.doi.org/10.2174/1566524022666220811161111	Print ISSN 1566-5240
Publisher Name Bentham Science Publisher	Online ISSN 1875-5666

Current Molecular Medicine

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

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