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./nMethods: 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./nResults: 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./nConclusion: 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.

中文翻译：

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红景天苷可以靶向P4HB介导的炎症和皮肤黑色素生成

理由：许多外部因素均可诱发皮肤黑色素生成和炎症。红景天苷（SAL）是景天科的主要活性成分，景天科是景天科的多年生草植物。这项研究评估了SAL对皮肤炎症和黑色素生成的影响及其分子机制。然后，它探讨了黑色素生成的分子机制在紫外线（UV）和炎性stimulation./n方法：VISIA皮肤分析成像系统和DermaLab仪器用于检测志愿者的黑色素减少和皮肤亮度改善率。紫外线治疗的昆明小鼠用于检测SAL对皮肤炎症和黑色素生成的影响。分子对接和Biacore用于验证SAL的目标。免疫荧光，荧光素酶报告基因检测，CO-IP，下拉，Western印迹，邻位连接检定（PLA），和qPCR用于研究由SAL调控对皮肤炎症和黑色素production./n的分子机制的结果：SAL可以抑制志愿者的炎症和黑色素生成。SAL还对紫外线治疗的昆明小鼠产生了保护作用。SAL可以抑制A375细胞中的酪氨酸酶（TYR）活性和TYR mRNA表达。SAL还可以通过靶向脯氨酰4-羟化酶β多肽（P4HB）来介导炎症和黑色素生成，从而调节干扰素调节因子1（IRF1）的泛素化降解。这项研究还表明IRF1和上游刺激因子1（USF1）可以形成转录复合体，以调节TYR mRNA的表达。IRF1还在紫外线和脂多糖诱导的条件下介导炎症反应和TYR表达。此外，SAL衍生物SAL-plus（1-（3,5-二羟基苯基）乙基-β-d-葡萄糖苷）对炎症和黑色素生成的作用要比SAL / n好。结论： SAL可通过靶向P4HB并调节IRF1 / USF1转录复合物的形成来抑制皮肤的炎症和黑色素生成。此外，SAL-plus可能是一种新的黑色素生成和炎症抑制剂。