1. Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin.
- Author
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Ding XJ, Zhang ZY, Jin J, Han JX, Wang Y, Yang K, Yang YY, Wang HQ, Dai XT, Yao C, Sun T, Zhu CB, and Liu HJ
- Subjects
- Adult, Animals, Cell Line, Tumor, Disease Models, Animal, Female, Glucosides therapeutic use, Healthy Volunteers, Humans, Hyperpigmentation immunology, Hyperpigmentation pathology, Interferon Regulatory Factor-1 metabolism, Male, Melanocytes drug effects, Melanocytes metabolism, Melanocytes radiation effects, Mice, Molecular Docking Simulation, Monophenol Monooxygenase antagonists & inhibitors, Monophenol Monooxygenase metabolism, Phenols therapeutic use, Procollagen-Proline Dioxygenase antagonists & inhibitors, Procollagen-Proline Dioxygenase metabolism, Protein Disulfide-Isomerases antagonists & inhibitors, Protein Disulfide-Isomerases metabolism, Skin drug effects, Skin immunology, Skin pathology, Skin radiation effects, Skin Aging drug effects, Skin Aging immunology, Skin Aging radiation effects, Skin Cream pharmacology, Skin Cream therapeutic use, Skin Lightening Preparations therapeutic use, Skin Pigmentation radiation effects, Transcriptional Activation drug effects, Ubiquitination drug effects, Ultraviolet Rays adverse effects, Upstream Stimulatory Factors metabolism, Young Adult, Glucosides pharmacology, Hyperpigmentation drug therapy, Melanins metabolism, Phenols pharmacology, Skin Lightening Preparations pharmacology, Skin Pigmentation drug effects
- Abstract
Rationale: Many external factors can induce the melanogenesis and inflammation of the skin. Salidroside (SAL) is the main active ingredient of Rhodiola , which is a perennial grass plant of the Family Crassulaceae. This study evaluated the effect and molecular mechanism of SAL on skin inflammation and melanin production. It then explored the molecular mechanism of melanin production under ultraviolet (UV) and inflammatory stimulation. Methods: VISIA skin analysis imaging system and DermaLab instruments were used to detect the melanin reduction and skin brightness improvement rate of the volunteers. UV-treated Kunming mice were used to detect the effect of SAL on skin inflammation and melanin production. Molecular docking and Biacore were used to verify the target of SAL. Immunofluorescence, luciferase reporter assay, CO-IP, pull-down, Western blot, proximity ligation assay (PLA), and qPCR were used to investigate the molecular mechanism by which SAL regulates skin inflammation and melanin production. Results: SAL can inhibit the inflammation and melanin production of the volunteers. SAL also exerted a protective effect on the UV-treated Kunming mice. SAL can inhibit the tyrosinase (TYR) activity and TYR mRNA expression in A375 cells. SAL can also regulate the ubiquitination degradation of interferon regulatory factor 1 (IRF1) by targeting prolyl 4-hydroxylase beta polypeptide (P4HB) to mediate inflammation and melanin production. This study also revealed that IRF1 and upstream stimulatory factor 1 (USF1) can form a transcription complex to regulate TYR mRNA expression. IRF1 also mediated inflammatory reaction and TYR expression under UV- and lipopolysaccharide-induced conditions. Moreover, SAL derivative SAL-plus (1-(3,5-dihydroxyphenyl) ethyl-β-d-glucoside) showed better effect on inflammation and melanin production than SAL. Conclusion: SAL can inhibit the inflammation and melanogenesis of the skin by targeting P4HB and regulating the formation of the IRF1/USF1 transcription complex. In addition, SAL-plus may be a new melanin production and inflammatory inhibitor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2020
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