Title: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
Volume: 23
Issue: 8
Author(s): Ruilian Xu, Xianyong Liu, Mengfei Tian and Diping Chen*
Affiliation:
- The First Clinical School, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China
Keywords:
Irritable bowel syndrome, atractylenolide‐I, colonic mucosal epithelial cell, miR-34a-5p, glucose metabolism, lactate dehydrogenase-A.
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.
