Protective Effect of Neochlorogenic Acid on Diabetic Nephropathy via Inflammation and Pyroptosis Suppression

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease. Neochlorogenic acid (nCGA), a polyphenolic compound present in various plant-based foods, has been recognized for its potent antioxidant and anti-inflammatory properties. However, its mechanistic effects on pyroptosis and microRNA signaling in the context of DN remain unclear. We investigated the molecular effects of nCGA on oxidative stress, inflammation, pyroptosis, and miRNA regulation in MES-13 mouse mesangial cells. nCGA enhanced Nrf2 activation, upregulated antioxidant genes, and suppressed ROS accumulation. It inhibited NF-κB signaling and reduced inflammatory proteins and also attenuated pyroptosis by downregulating NLRP3, GSDMD, caspase-1, and IL-1β. MicroRNA profiling revealed dual regulation: nCGA upregulated miR-30a, suppressing NF-κB/TNF-α pathways, and downregulated miR-709, thereby restoring the Nrf2-mediated antioxidant defense. Transfection with miR-30a mimics or miR-709 inhibitors reproduced these protective effects. These findings highlight the dual miRNA-mediated regulation, providing novel therapeutic insights into mitigating oxidative stress and inflammation in diabetic nephropathy.