Curcuma longa improves endothelial glycocalyx integrity and redox-inflammatory pathways in type 2 diabetes mellitus: a randomized double-blind placebo-controlled study

PURPOSE: This randomized, double‐blind, placebo‐controlled trial investigated the effects of Curcuma longa extract (CLE) supplementation on vascular, redox‐inflammatory biomarkers, and neuropathy symptoms in adults with type 2 diabetes mellitus (T2DM). METHODS: Seventy‐six adults with T2DM were randomized to receive CLE (1200 mg/day) or placebo for three months. Plasma concentrations of hyaluronic acid (HA), syndecan‐1 (SDC1), syndecan‐4 (SDC4), matrix metalloproteinases (MMP‐2 and MMP‐9), thioredoxin‐1 (Trx1), thioredoxin‐binding protein‐2 (TBP2), sirtuin‐1 (SIRT1), nuclear factor erythroid 2–related factor 2 (Nrf2), and the p65 subunit of nuclear factor kappa B (NF‐κB p65) were measured at baseline and post‐intervention. Neuropathy symptoms were assessed using a validated questionnaire. RESULTS: Baseline characteristics were comparable between groups. After 3 months, CLE supplementation resulted in a significant reduction in neuropathy symptom score compared with placebo (P = 0.048). CLE significantly reduced markers of endothelial glycocalyx shedding, including SDC1 (66.5 vs. 113.0 ng/mL; P = 0.001), SDC4 (155.1 vs. 225.5 pg/mL; P = 0.040), and HA (259.8 vs. 371.7 ng/mL; P = 0.002), as well as MMP‐2 (198.4 vs. 233.3 ng/mL; P < 0.001) and MMP‐9 (1.2 vs. 2.0 ng/mL; P < 0.001). In parallel, CLE increased antioxidant/redox markers Trx1, SIRT1, and Nrf2 (all P < 0.05) and reduced TBP2 and NF‐κB p65 levels (both P < 0.001), indicating coordinated modulation of vascular, redox, and inflammatory pathways. CONCLUSION: Short‐term supplementation with CLE was associated with favorable modulation of vascular and redox‐inflammatory biomarkers and improvement in neuropathy symptoms in adults with T2DM. These findings support the role of CLE as a promising bioactive nutritional supplement for the prevention and management of vascular and neuropathic complications associated with diabetes.