title: Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling.
abstract: Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway.
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.|Department of Chinese Medicine, Lanzhou General Hospital, Gansu 730050, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32611, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yani
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zifei
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.|E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai 201203, China.
authors.forename: Changquan
authors.initials: C
authors.lastname: Ling
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism; D036145:Ginsenosides / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D036145:Ginsenosides; D005938:Glucocorticoids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D003907:Dexamethasone; C533423:HDAC2 protein, human; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; C035054:ginsenoside Rg1