Eugenol Mitigates High-Glucose and High-Lipid-Induced Changes in Skin Fibroblasts

Eugenol, a phenolic compound derived from clove oil, has garnered considerable attention for its anti-aging properties, particularly in relation to skin health. This study investigated the effects of eugenol on human dermal fibroblasts exposed to high-glucose and high-lipid (HGHL) conditions—25 mM glucose and 400 µM palmitic acid—to mimic premature skin aging. After establishing metabolic stress, fibroblasts were treated with 15 µM eugenol either as a co-treatment or post-treatment. A comprehensive set of assays was conducted, including MTT for cell viability, β-galactosidase staining for senescence, qPCR for inflammatory cytokines and extra-cellular matrix (ECM)-related gene expression, apoptosis and cell cycle analyses, and wound healing assays. Eugenol significantly reduced oxidative stress, inflammation, and cellular senescence in fibroblasts under HGHL conditions. IL-1β and COX-2 expression levels were significantly decreased in both treatment strategies. IL-6 expression was significantly reduced in post-treatment, while TNF-α decreased in co-treatment. Regarding ECM-related genes, COL3A1 expression significantly increased in untreated fibroblasts treated with eugenol, and elastin expression was significantly elevated in co-treatment with HGHL. Additionally, under HGHL conditions, eugenol inhibited apoptosis and positively influenced cell cycle progression, contributing to improved cell survival. Overall, eugenol can be considered as natural compound mitigating signs of metabolic stress-induced skin aging often associated with type II diabetes.