Protective roles of psilocybin and eugenol in mitigating the effects of high-glucose and high-lipid treatment of human skin fibroblasts (BJ-5ta)

Abstract

Skin aging, particularly under conditions of metabolic stress, is driven by a complex interplay of oxidative stress, inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) degradation. This thesis investigates the protective effects of two natural compounds—eugenol, a phenolic compound derived from clove oil, and psilocybin, a serotonergic tryptamine alkaloid—against premature aging in human dermal fibroblasts (BJ-5Ta) exposed to high-glucose and high-lipid (HGHL) conditions (25 mM glucose and 400 µM palmitic acid).

Both compounds were assessed using co-treatment and post-treatment approaches. A wide range of assays, including MTT, β-galactosidase staining, qPCR for inflammatory and ECM-related genes, flow cytometry for apoptosis and cell cycle, and wound healing assays, were employed to evaluate cellular viability, senescence, inflammation, and ECM remodeling.

Eugenol treatment significantly reduced oxidative stress, inflammation (notably IL-1β, COX-2, and TNF-α), and cellular senescence, while upregulating ECM components such as COL3A1 and elastin (ELN). Psilocybin also preserved cell viability, reduced apoptosis, mitigated senescence markers, downregulated IL-1β, IL-6, and COX-2, and promoted ELN expression under HGHL-induced stress.

Together, the findings demonstrate that both eugenol and psilocybin exert anti-inflammatory, antioxidative, and anti-senescent effects, helping to preserve dermal fibroblast integrity and function under metabolically stressful conditions. These results highlight the therapeutic potential of natural bioactive compounds in preventing or delaying skin aging and pave the way for future clinical research on their use in dermatological applications.