title: Salidroside suppresses solar ultraviolet-induced skin inflammation by targeting cyclooxygenase-2.
abstract: Solar ultraviolet (SUV) irradiation causes skin disorders such as inflammation, photoaging, and carcinogenesis. Cyclooxygenase-2 (COX-2) plays a key role in SUV-induced skin inflammation, and targeting COX-2 may be a strategy to prevent skin disorders. In this study, we found that the expression of COX-2, phosphorylation of p38 or JNKs were increased in human solar dermatitis tissues and SUV-irradiated human skin keratinocyte HaCaT cells and mouse epidermal JB6 Cl41 cells. Knocking down COX-2 inhibited the production of prostaglandin E2 (PGE2), the phosphorylation of p38 or JNKs in SUV-irradiated cells, which indicated that COX-2 is not only the key enzyme for PGs synthesis, but also an upstream regulator of p38 or JNKs after SUV irradiation. The virtual ligand screening assay was used to search for natural drugs in the Chinese Medicine Database, and indicated that salidroside might be a COX-2 inhibitor. Molecule modeling indicated that salidroside can directly bind with COX-2, which was proved by in vitro pull-down binding assay. Ex vivo studies showed that salidroside has no toxicity to cells, and inhibits the production of PGE2, phosphorylation of p38 or JNKs, and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) caused by SUV irradiation. In vivo studies demonstrated that salidroside attenuates the skin inflammation induced by SUV. In brief, our data provided the evidences for the protective role of salidroside against SUV-induced inflammation by targeting COX-2, and salidroside might be a promising drug for the treatment of SUV-induced skin inflammation.
authors.affiliation: Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.|Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Changshu
authors.initials: C
authors.lastname: Ke
authors.affiliation: Department of Pathology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.
authors.forename: Jinguang
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.
authors.forename: Mingmin
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Dermatology of the General Hospital of Air Force, Beijing, 100142, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011855:Radiodermatitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D005960:Glucosides; D010636:Phenols; D051546:Cyclooxygenase 2; C009172:rhodioloside
keywords: cyclooxygenase-2; p38; salidroside; skin inflammation; solar UV