Enzyme-assisted Rosa davurica mitigates UV-induced skin photodamage by modulating apoptosis through Nrf2/ARE and MAPK/NF-κB pathways

Abstract

Exposure to UV irradiation results in abnormal, extensive apoptosis of skin cells. This excessive cell death can promote inflammation and alter the microenvironment, increasing the risk of skin cancer. Despite extensive research, few materials are effective at simultaneously protecting against both UVA and UVB irradiation. This study aims to develop dual-action material using enzyme-assisted extraction of Rosa davurica Pall (RD) to prevent skin photodamage caused by UVA and UVB irradiation. Three different enzymes were used to assist the extraction of RD, followed by an analysis of the changes in active component levels. Skin photodamage models were established by exposing Normal Human Dermal Fibroblasts (NHDF) and HaCaT cells to UVA and UVB irradiation. The impact of enzyme-assisted extracted RD (ERD) on Reactive Oxygen Species (ROS) production and cell apoptosis was assessed using Flow Cytometry. The effects of ERDs on inflammatory cytokines were measured using ELISA, and RT-PCR was used to evaluate its impact on apoptotic gene expression in photodamaged cells. Furthermore, the impact of ERDs on the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Antioxidant response element (ARE) and Mitogen-activated protein kinases (MAPK)/Nuclear factor-κB (NF-κB) signaling pathways was assessed through Western blot analysis. Finally, the impact of ERDs on full-thickness artificial skin tissue after UV irradiation was assessed using hematoxylin and eosin (H&E) staining. Furthermore, leveraging the experimental results, network pharmacology was utilized to explore the potential of ERDs in preventing skin cancer. Enzyme-assisted extraction enhanced the bioactive components of RD. ERDs effectively reduced ROS levels and suppressed the secretion of Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, and IL-6 by modulating the Nrf2/ARE and inhibiting the MAPK/NF-κB signaling pathways. This mechanism promoted the expression of the anti-apoptotic gene Bcl-2 and decreased the activity of proapoptotic genes BAX, caspase-3, and caspase-9, thereby countering UV-induced apoptosis. Additionally, staining results demonstrated that ERDs effectively repaired UV-induced photodamage and maintained the integrity of skin structure. ERDs provides comprehensive protection against photodamage induced by UVA and UVB irradiation, demonstrating its potential as an effective photoprotective material and possibly in preventing skin cancer.