title: Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP-1 and activation of Nrf2-ARE antioxidant system.
abstract: Solar ultraviolet (UV) radiation-induced reactive oxidative species is mainly responsible for the development of photoageing. Rosmarinic acid was one of the main bioactive components detected in Thymus vulgaris (TV) we extracted. In this study, UVB-induced skin damages have been shown to be ameliorated by treatment with TV in hairless mice (HR-1) skin, demonstrated by decreased matrix metalloproteinases (MMPs) and increased collagen production. However, the underlying molecular mechanism on which TV acted was unclear. We examined the photoprotective effects of TV against UVB and elucidated the molecular mechanism in normal human dermal fibroblasts. Thymus vulgaris remarkably prevented the UVB-induced reactive oxygen species and lactate dehydrogenase. Dose-dependent increase in glutathione, NAD(P)H: quinone oxidoreductase1 and heme oxygenase-1, by TV was confirmed by increased nuclear accumulation of Nrf2. Furthermore, 5-Methoxyindole-2-carboxylic acid was introduced as a specific inhibitor of dihydrolipoyl dehydrogenase (DLD). We demonstrated that Nrf2 expression was regulated by DLD, which was a tricarboxylic acid cycle-associated protein that decreased after UVB exposure. Besides, TV significantly diminished UVB induced phosphorylation of mitogen activated protein kinases pathway, containing extracellular signal-regulated kinase, Jun N-terminal kinase and p38, which consequently reduced phosphorylated c-fos and c-jun. Our results suggest that TV is a potential botanical agent for use against UV radiation-induced oxidative stress mediated skin damages.
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Zhengwang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Eunson
authors.initials: E
authors.lastname: Hwang
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Seul A
authors.initials: SA
authors.lastname: Seo
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Oriental Medicinal Biotechnology, College of Life Science, Kyung Hee University Global Campus, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Tae-Hoo
authors.initials: TH
authors.lastname: Yi
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics*; D000975:Antioxidants / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000528:radiation effects; D004549:Elastin / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008812:Mice, Hairless; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010936:Plant Extracts / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects; D013194:Staining and Labeling; D046930:Thymus Plant / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1; D004549:Elastin; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1
keywords: 
  MAPK
  ; 
  Thymus vulgaris
  ; 
  UVB
  ; AP-1; Nrf2