Antioxidant and Anti-Inflammatory Benefits of Gymnema inodorum Leaf Extract in Human Umbilical Vein Endothelial Cells Under Peroxynitrite Stress

Abstract

Endothelial dysfunction driven by oxidative and nitrosative stress is a critical factor in the pathogenesis of diabetes-related vascular complications. This study investigated the antioxidant and anti-inflammatory effects of Gymnema inodorum leaf (GiL) extract and its flavonoid constituents, kaempferol and quercetin, on human umbilical vein endothelial cells (HUVECs) exposed to peroxynitrite-induced stress. Peroxynitrite exposure significantly reduced the mRNA levels of antioxidant enzymes (e.g., catalase, glutathione peroxidase 1, superoxide dismutase 1, and superoxide dismutase 2) while increasing the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-10, and interleukin-12), ultimately leading to oxidative stress and cellular damage. Treatment with GiL extract reversed these effects by enhancing the defenses of antioxidants through the upregulation of enzymatic mRNA expression and suppressing inflammation via the downregulation of cytokine gene expression. The flavonoid constituents of the extract were identified as the active compounds responsible for these protective effects, with kaempferol and quercetin exhibiting significant free radical scavenging activity and the modulation of inflammatory signaling pathways. High doses of GiL extract showed greater efficacy in restoring cellular homeostasis and preventing oxidative damage. These findings underscore the potential of Gymnema inodorum as a source of bioactive compounds for preventing and managing endothelial dysfunction and other oxidative stress-related complications in diabetes.