Atractylodes-I Overcomes the Oxidative Stress-induced Colonic Mucosal Epithelial Cells Dysfunction to Prevent...

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Irritable bowel syndrome (IBS) is a brain-gut disorder with unclear molecular mechanisms.
• Atractylenolide-I (ATL-I), from Rhizoma Atractylodes Macrocephalae, is a known anti-tumor compound.
• The role of ATL-I in IBS-related colonic mucosal epithelial cell (CMEC) dysfunction is unexplored.

Purpose of the Study:

• To investigate the effects and molecular mechanisms of ATL-I on oxidative stress-induced CMEC dysfunction in IBS.
• To elucidate the role of miR-34a-5p and lactate dehydrogenase-A (LDHA) in this process.
• To determine if ATL-I can modulate the miR-34a-5p-LDHA axis to alleviate IBS pathology.

Main Methods:

• Analysis of colonic tissues from IBS patients for miR-34a-5p and glucose metabolism enzyme expression.
• In vitro studies using NCM460 cells treated with H2O2 to mimic oxidative stress.
• Bioinformatics, Western blot, luciferase assays, and rescue experiments to confirm molecular targets and pathways.
• Treatment with ATL-I to assess its effects on oxidative stress, miR-34a-5p, LDHA, and glucose metabolism.

Main Results:

• IBS patient tissues showed upregulated miR-34a-5p and suppressed glucose metabolism.
• H2O2-induced oxidative stress in NCM460 cells increased miR-34a-5p and inhibited glucose metabolism.
• ATL-I treatment reversed these oxidative stress-induced changes.
• miR-34a-5p was identified as a direct target of LDHA, inhibiting glucose metabolism.
• ATL-I normalized glucose metabolism and CMEC function by modulating the miR-34a-5p-LDHA pathway.

Conclusions:

• ATL-I effectively alleviates oxidative stress-induced CMEC dysfunction in an IBS model.
• The mechanism involves the regulation of the miR-34a-5p-LDHA-glucose metabolism axis.
• ATL-I represents a potential therapeutic agent for IBS by targeting this pathway.