Ruilian Xu, Xianyong Liu, Mengfei Tian and Diping Chen* Pages 825 - 833 ( 9 )
<p> Background: Irritable bowel syndrome (IBS) is a known brain-gut disorder. Currently, the molecular and cellular mechanisms of IBS remain unclear. <i>Atractylenolide‐I</i> (ATL-I) is a majorly bioactive component extracted from <i>Rhizoma Atractylodes Macrocephalae</i>. </p><p> 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 H<sub>2</sub>O<sub>2</sub> treatment which mimics <i>in vitro</i> 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. </p><p> 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. </p><p> 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.</p>
Irritable bowel syndrome, atractylenolide‐I, colonic mucosal epithelial cell, miR-34a-5p, glucose metabolism, lactate dehydrogenase-A.