Guggulsterone attenuates UVB-induced oxidative stress and inflammation in keratinocyte HaCaT cells via HO-1 induction

Ultraviolet B (UVB) radiation is a potent environmental stressor known to induce oxidative damage and inflammatory responses in skin keratinocytes, contributing to photoaging and photocarcinogenesis. Guggulsterone (GS), a phytosterol derived from Commiphora mukul, exhibits established antioxidant and anti-inflammatory properties, yet its protective role in UVB-induced skin injury remains poorly understood. In this study, we investigated the protective effects of GS against UVB-induced cellular damage in HaCaT human keratinocytes and explored the underlying mechanism with a focus on heme oxygenase-1 (HO-1) induction. GS pretreatment significantly reduced UVB-induced intracellular reactive oxygen species (ROS) generation, DNA fragmentation, and loss of cell viability in a dose-dependent manner. Additionally, GS suppressed the expression of pro-inflammatory cytokines, including TNF-α and IL-6, at both mRNA and protein levels. Mechanistic analyses revealed that GS markedly upregulated HO-1 expression, and inhibition of HO-1 with tin protoporphyrin IX (SnPP) attenuated the cytoprotective and anti-inflammatory effects of GS. These findings suggest that GS confers photoprotective effects against UVB-induced oxidative and inflammatory damage via HO-1 activation. GS may represent a promising candidate for the development of topical agents targeting UVB-induced oxidative and inflammatory skin damage.