Cytoprotective Effects of Gymnema inodorum Against Oxidative Stress-Induced Human Dermal Fibroblasts Injury: A Potential Candidate for Anti-Aging Applications

Abstract

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H2O2-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H2O2-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. © 2025 by the authors.