Cannabidiol Attenuates UVB-Induced Skin Inflammation via STAT3/c-Jun Suppression and Silicone Polymer—Based Topical Delivery 2330062

Abstract Introduction UVB radiation induces epidermal damage and inflammatory responses through immune-mediated pathways in the skin. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has demonstrated anti-inflammatory effects in various disease models; however, its therapeutic application in UVB-induced skin inflammation remains limited by poor stability and low bioavailability, largely due to oxidative and photodegradative instability. Methods This study was designed with two objectives. First, we aimed to elucidate the intrinsic anti-inflammatory mechanism of CBD in UVB-induced keratinocyte inflammation, with a particular focus on STAT3/c-Jun signaling axis. Second, we sought to evaluate a silicone polymer—based delivery strategy to improve the therapeutic efficacy of CBD in an in vivo UVB-induced skin inflammation model. Results To address the first objective, we investigated the effects of CBD on UVB-induced inflammatory responses in the human keratinocyte cell line. UVB irradiation markedly increased IL-6 expression, whereas CBD treatment significantly reduced IL-6 production at both the transcriptional and protein levels. CBD suppressed UVB-induced STAT3 and c-Jun phosphorylation, implicating a previously poorly understood STAT3—c-Jun signaling axis in its anti-inflammatory effects. To address the second one, a silicone polymer—formulated CBD was topically applied to the dorsal skin of UVB-irradiated hairless mice. This formulation was used to assess changes in epidermal thickness and inflammatory skin pathology, thereby evaluating the capacity of polymer-based delivery to enhance local therapeutic efficacy in vivo. Conclusion These findings demonstrate that CBD attenuates UVB-induced skin inflammation through modulation of STAT3/c-Jun—dependent signaling in keratinocytes and that a silicone polymer—based delivery represents an effective strategy to overcome stability limitations and improve the in vivo efficacy of topical CBD for UVB-mediated inflammatory skin conditions. Funding Source n/a Topic Categories Immune Mechanisms of Human Disease (HUM)