title: Z-ligustilide ameliorated ultraviolet B-induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO-1 and suppression of NF-κB pathway.
abstract: Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z-ligustilide (Z-lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB-induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z-lig significantly rescued UVB-induced NHEKs damage in a dosage-dependent manner. Pretreatment of NHEKs with Z-lig inhibited UVB-induced ROS production in NHEKs. Both silencing the nuclear factor E2-related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase-1 (HO-1) inhibitor, cancelled the inhibitory effect of Z-lig on UVB-induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z-lig reduced UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators (IL-6, IL-8 and MCP-1) production at both mRNA and protein level. In the presence of Z-lig, UVB-induced NF-κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z-lig can suppress UVB-induced ROS generation through Nrf2/HO-1 upregulation and inflammation by suppressing the NF-κB pathway, suggesting that Z-lig may be beneficial in protecting skin from UVB exposure.
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.|Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Zhouwei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Morino-Koga
authors.affiliation: Department of Dermatology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D020868:Gene Silencing; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism*; D014162:Transfection; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C027820:ligustilide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D015107:4-Butyrolactone
keywords: NF-κB; Nrf2; Z-ligustilide; keratinocytes; ultraviolet B