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

• Published in: British journal of pharmacology Vol. 179; no. 19; pp. 4722 - 4737
• Main Authors: Dai, Xintong, Jin, Jing, Jia, Yan, Yang, Kai, Han, Jingxia, Zhang, Zhiyuan, Ding, Xiujuan, Yao, Cheng, Sun, Tao, Zhu, Caibin, Liu, Huijuan
• Format: Journal Article
• Language: English
• Published: London Blackwell Publishing Ltd 01.10.2022
• Subjects: Aging; Agonists; Animal models; Cell culture; Collagen; Enzyme-linked immunosorbent assay; Flow cytometry; Immunofluorescence; Inflammation; Irritation; MAP kinase; Matrix metalloproteinase; Metalloproteinase; Pigmentation; Proteomics; RAR‐γ selective agonist; Retinoic acid; retinoic acid receptor γ (RAR‐γ); Retinoic acid receptors; Signal transduction; Skin; tectorigenin; Ultraviolet radiation; UVA‐induced skin damage; Vitamin A; Western blotting
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.15902

Background and Purpose 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. Experimental Approach 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. Key Results 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. Conclusions and Implications 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.