Coreopsis tinctoria: A Natural Remedy Against UVA-Induced Photodamage in HaCaT via Nrf2/HO-1 Mediated Endoplasmic Reticulum Stress Alleviation
Solar ultraviolet (UV) radiation includes UVB (290-320 nm) and UVA (320-400 nm) wavelengths. While UVA is less energetic than UVB, it causes significant damage to both dermal and epidermal layers through acute and chronic exposure, leading to the accumulation of misfolded proteins and triggering endoplasmic reticulum (ER) stress. Mild exposure may activate a protective unfolded protein response, but prolonged exposure can result in cellular apoptosis. UVA radiation induces ER stress primarily through reactive oxygen species (ROS) production, activating downstream signaling pathways. Thus, identifying compounds that alleviate UVA-induced ER stress is crucial. Coreopsis tinctoria (CT), a traditional remedy from Xinjiang, China, contains bioactive compounds like flavonoids and polysaccharides, known for their antioxidant and anti-inflammatory effects.This study aims to evaluate the effectiveness of CT extract in reducing UVA-induced skin photodamage in human keratinocytes (HaCaT) by alleviating ER stress and apoptosis.We conducted transcriptomics analysis on UVA-exposed HaCaT cells, with and without CT extract treatment. Gene Ontology (GO) enrichment analysis highlighted differentially expressed genes associated with the 'response to ER stress' and 'cellular response to misfolded proteins' in the CT-treated cells compared to untreated UVA-irradiated cells. Western blotting, RT-qPCR, and immunofluorescence confirmed that markers related to ER stress, such as CHOP, pIRE1, and ATF6, were significantly downregulated following CT treatment. Additionally, apoptosis-related markers, including BCL2, cleaved-caspase 3, and cleaved-caspase 9, were reduced, and apoptosis assays using flow cytometry corroborated these findings. Notably, the application of tunicamycin, an ER stress inducer, negated the protective effects of CT against UVA-induced apoptosis and inflammation. Meanwhile, we identified the crosstalk pathway of Nrf2/HO-1 and ER stress by CT in eliciting the downstream antioxidant and detoxification targets. Furthermore, high-performance liquid chromatography (HPLC) analysis identified marein as the active compound responsible for the observed alleviation of ER stress following UVA exposure.These findings suggest that CT may serve as a promising therapeutic agent for protecting human keratinocytes from UVA-induced damage by mitigating ER stress and apoptosis. Overall design: RNA-seq profiling of HaCaT (Human Keratinocyte) cells subjected to UVA irradiation. After UVA irradiation with the addition of CT, we wanted to investigate whether CT had the ability of anti-photodamage in HaCaT (Human Keratinocyte) cell, especially in ER stress. Then we performed gene expression profiling analysis using data obtained from RNA seq of 3 different treated ways (control group (NC), UVA treated group, UVA and CT co-treated group) in Hacat cell.