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Coreopsis tinctoria: A Natural Remedy Against UVA-Induced Photodamage in HaCaT via Nrf2/HO-1 Mediated Endoplasmic Reticulum Stress Alleviation

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296781 | GEO | 2025/12/31

REPOSITORIES: GEO

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Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin. 24 hours after UVA, UVB and ssUV irradiation, a 1 cm2 uniform section of skin was excised from the dorsal surface of irradiated and control mice. Total RNA was then extracted from the whole skin using TRIzol reagent (Gibco Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturerâ??s instructions, purified, DNase treated and reverse transcribed into cDNA. For the microarray study a direct incorporation of Cyanine 3-dCTP and Cyanine 5-dCTP fluorescent dyes (Perkin Elmer Life Sciences, Inc. Boston, MA, USA) was used for cDNA synthesis. For each UV dose, a reference design was used to compare an unirradiated control against an irradiated sample. Microarray experiments used compugen 22k mouse oligonucleotide microarray slides (The Clive and Vera Ramaciotti Centre for Gene Function Analysis, Sydney Australia (http://www.ramaciotti.unsw.edu.au). Lower and higher UVA doses were used. C57BL/6 mice were irradiated with lower UVA, higher UVA, UVB, or ssUV; Balb/C mice were irradiated with lower or higher UVA. Experiments were replicated 6 times for each UV dose. A fluorescent dye swap was done for each alternate hybridisation to reduce systematic dye bias of incorporated fluorescent dyes.

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Coreopsis tinctoria: A Natural Remedy Against UVA-Induced Photodamage in HaCaT via Nrf2/HO-1 Mediated Endoplasmic Reticulum Stress Alleviation

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