RESUMEN
Skin homeostasis is predominantly compromised by exposure to UV-B irradiation, leading to several physiopathological processes at cellular and tissue levels that deteriorate skin function and integrity. The current study investigated the photo-protective role of seabuckthorn fruit pulp (SBT) extract against UV-B-induced damage in primary human skin fibroblasts (HDFs) and Balb/C mice skin. We subjected HDFs and Balb/C mice to UV-B irradiation and measured multiple cellular damage indicators. We found that UV-B-irradiated HDFs treated with SBT had a considerably greater survival rate than cells exposed to UV-B radiation alone. The UV-B irradiation-induced ROS generation led to the degradation of the extracellular matrix, inflammation, DNA damage, endoplasmic reticulum (ER) stress, and apoptosis. SBT treatment significantly reduced these manifestations. Topical application of SBT alleviated UV-B-induced epidermal thickening, leukocyte infiltration, and degradation of extracellular matrix in Balb/c mice skin. Based on our results, we conclude that SBT has the potential to be developed as a therapeutic/cosmetic remedy for the prevention of skin photo-damage.
Asunto(s)
Daño del ADN , Estrés del Retículo Endoplásmico , Fibroblastos , Hippophae , Ratones Endogámicos BALB C , Estrés Oxidativo , Extractos Vegetales , Piel , Rayos Ultravioleta , Animales , Ratones , Hippophae/química , Fibroblastos/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacosRESUMEN
Ultraviolet-B (UV-B) irradiation has been reported to cause oxidative stress and inflammation-mediated skin photo-damage. Furthermore, mitochondrial dynamics have been implicated to play a critical role in these processes. For the first time, we describe in this study how UVB-induced aberrant mitochondrial dynamics and inflammation interact in primary human dermal fibroblasts (HDFs). Our findings demonstrated that UV-B irradiation induced -impairment in mitochondrial dynamics by increasing mitochondrial fragmentation in HDFs. Imbalanced mitochondrial dynamics lead to the activation of NFкB and pro-inflammatory cytokines. The current study further aimed to investigate the protective effect of Naringenin (a naturally occurring flavonoid isolated from Sea buckthorn fruit pulp) against UV-B-induced mitochondrial fragmentation and inflammation in HDFs and Balb/c mice. Although Naringenin has been shown to have anti-inflammatory and antioxidant potential, its effects and mechanisms of action on UVB-induced inflammation remained unclear. We observed that Naringenin restored the UV-B-induced imbalance in mitochondrial fission and fusion in HDFs. It also inhibited the phosphorylation of NFкB and reduced the generation of pro-inflammatory cytokines. Naringenin also alleviated UV-B-induced oxidative stress by scavenging the reactive oxygen species and up-regulating the cellular antioxidant enzymes (Catalase and Nrf2). Topical application of Naringenin to the dorsal skin of Balb/c mice exposed to UV-B radiation prevented mitochondrial fragmentation and progression of inflammatory responses. Naringenin treatment prevented neutrophil infiltration and epidermal thickening in mice's skin. These findings provide an understanding for further research into impaired mitochondrial dynamics as a therapeutic target for UV-B-induced inflammation. Our findings imply that Naringenin could be developed as a therapeutic remedy against UVB-induced inflammation.