Curcumin, the Bioactive Compound of Turmeric, Boosts Cellular Antioxidant Defense via the miR-22-3p/MCAT Axis

Curcumin, the major bioactive polyphenol derived from the edible rhizome turmeric (Curcuma longa L.), is recognized for its health-promoting properties. Despite well-documented antioxidant effects, its molecular mechanisms, particularly those involving post-transcriptional regulation, remain incompletely understood. This in vitro study identifies a novel microRNA-mediated pathway contributing to the antioxidant activity of curcumin in human hepatic LO2 cells. Curcumin treatment downregulated the stress-responsive microRNA miR-22-3p. Bioinformatics analysis and a dual-luciferase reporter assay identified malonyl-CoA-acyl carrier protein transacylase (MCAT), a mitochondrial enzyme, as a direct target of miR-22-3p. Modulation of this axis reduced intracellular reactive oxygen species (ROS), enhanced total reducing capacity, increased activities of key antioxidant enzymes (SOD, CAT, GPx), and improved mitochondrial bioenergetics without altering membrane potential. Crucially, siRNA-mediated knockdown of MCAT attenuated the ROS-scavenging effect of curcumin. These findings reveal a mechanistic pathway wherein curcumin downregulates miR-22-3p, resulting in upregulation of MCAT and enhanced mitochondrial antioxidant defense. This work broadens the understanding of curcumin's bioactivity from direct radical scavenging to include the post-transcriptional fine-tuning of mitochondrial metabolism. The study establishes a molecular framework for further exploration of curcumin's potential in alleviating oxidative stress.