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

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). 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. 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. 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.