A non-retinol retinoic acid receptor-γ (RAR-γ/NR1B3) selective agonist, tectorigenin, can effectively inhibit the ultraviolet A-induced skin damage.

Xintong Dai, Jing Jin, Yan Jia, Kai Yang, Jingxia Han, Zhiyuan Zhang, Xiujuan Ding, Cheng Yao, Tao Sun, Caibin Zhu, Huijuan Liu

British journal of pharmacology 2022 Oct

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Long-term ultraviolet (UV) exposure can cause inflammation, pigmentation and photoaging. All-trans retinoic acid (ATRA/tretinoin) is a commonly used retinoic acid receptor (RAR) agonist in the clinical treatment of UV-induced skin problems. However, the use of such drugs is often accompanied by systemic adverse reactions caused by nonspecific activation of RARs. Therefore, this study was designed to screen for a novel RAR-γ-selective agonist with high safety. Molecular docking, dynamic simulation and Biacore were used to screen and identify novel RAR-γ-selective agonists. RT-PCR, ELISA, western blotting, immunofluorescence staining, flow cytometry and proteomic analysis were used to detect the effects of these novel RAR-γ selective agonists on UVA-induced inflammation and photoaging cell models. UVA-induced mouse models were used to evaluate the effects of tectorigenin on skin repair, ageing and inflammation. Tectorigenin is a novel RAR-γ-selective agonist, which inhibits UV-induced oxidative damage, inflammatory factor release and matrix metalloproteinase (MMP) production. Tectorigenin can also reverse the UVA-induced loss of collagen. The results of the signalling pathway research showed that tectorigenin mainly affects the MAPK/JNK/AP-1 pathway. In animal experiments, tectorigenin showed better anti-inflammatory and anti-photoaging effects, and caused less skin irritation than ATRA. Nano-particle loaded tectorigenin significantly improved the utilization of tectorigenin. Tectorignen is a non-retinol RAR-γ-selective agonist that can inhibit UV-induced skin damage and could be developed as a safe pharmaceutical component for the prevention of photoaging and skin inflammation. © 2022 British Pharmacological Society.

Citation

Xintong Dai, Jing Jin, Yan Jia, Kai Yang, Jingxia Han, Zhiyuan Zhang, Xiujuan Ding, Cheng Yao, Tao Sun, Caibin Zhu, Huijuan Liu. A non-retinol retinoic acid receptor-γ (RAR-γ/NR1B3) selective agonist, tectorigenin, can effectively inhibit the ultraviolet A-induced skin damage. British journal of pharmacology. 2022 Oct;179(19):4722-4737