Protective effect of isoquercitrin on UVB-induced injury in HaCaT cells and mice skin through anti-inflammatory, antioxidant, and regulation of MAPK and JAK2-STAT3 pathways

Abstract

Natural products are favored in the study of skin photodamage protection recently. Isoquercetin, namely 3-O-glucoside of quercetin, can be isolated from various plant species. In present research, the protective effect of isoquercitrin on UVB-induced injury in cells and mice skin were investigated. Our study reveals that 400 μM of isoquercitrin exhibits the best viability on UVB-irradiated HaCaT cells, and beneficial effects against oxidative stress UVB-induced in skin tissue by decreasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and simultaneously enhancing the activity of superoxide dismutase (SOD). Additionally, isoquercitrin was identified as an anti-inflammatory agent by reducing the level of COX-2 by Western blot analysis, and inflammatory cytokines such as IL-6, IL-1β, and TNF-α by ELISA, and UVB-induced epidermal thickening evidenced by H&E staining. It also effectively prevented UVB-induced collagen fibers from degradation identified by Masson staining. Isoquercitrin significantly inhibited MAPK pathway by downregulating the levels of AP-1, MMP-1, MMP-3, phospho-p38, phospho-JNK, phospho-ERK, cleaved caspase-9, cleaved caspase-3, and JAK2-STAT3 pathway by western blot analysis. In conclusion, isoquercitrin pretreatment protected mice skin from UVB irradiation-induced injury effectively, and the underlying mechanism may involve MAPK and JAK2-STAT3 signaling pathways.

Keywords: JAK2‐STAT3; MAPK; UVB; antioxidant; anti‐inflammatory; isoquercitrin.