Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin

Autor: Jing Jin, Cheng Yao, Cai-Bin Zhu, Hongqi Wang, Yuyan Yang, Huijuan Liu, Tao Sun, Jingxia Han, Zhi-Yuan Zhang, Yan Wang, Xintong Dai, Xiujuan Ding, Kai Yang
Rok vydání: 2020
Předmět:
Male
Tyrosinase
Skin Lightening Preparations
Skin Cream
Medicine (miscellaneous)
Skin Pigmentation
Proximity ligation assay
Melanin
Mice
chemistry.chemical_compound
prolyl 4-hydroxylase beta polypeptide (P4HB)
Glucosides
Hyperpigmentation
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
Skin
integumentary system
medicine.diagnostic_test
Monophenol Monooxygenase
Chemistry
interferon regulatory factor 1 (IRF1)
Salidroside
P4HB
Healthy Volunteers
Cell biology
Molecular Docking Simulation
Melanocytes
Female
medicine.symptom
Research Paper
Adult
Transcriptional Activation
Ultraviolet Rays
Procollagen-Proline Dioxygenase
Protein Disulfide-Isomerases
Inflammation
tyrosinase
upstream stimulatory factor 1 (USF1)
Young Adult
Phenols
Western blot
Cell Line
Tumor
parasitic diseases
medicine
Animals
Humans
Melanins
Ubiquitination
Skin Aging
Disease Models
Animal
IRF1
Upstream Stimulatory Factors
Interferon Regulatory Factor-1
Zdroj: Theranostics
ISSN: 1838-7640
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: