title: Sargahydroquinoic acid inhibits TNFα-induced AP-1 and NF-κB signaling in HaCaT cells through PPARα activation.
abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γ's role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.
authors.affiliation: Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors.forename: Youngsic
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors.forename: Yujung
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors.forename: Min Cheol
authors.initials: MC
authors.lastname: Kim
authors.affiliation: Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340, Republic of Korea.
authors.forename: Hak Cheol
authors.initials: HC
authors.lastname: Kwon
authors.affiliation: College of Korean Medicine, Gachon University, Seongnam 461-701, Republic of Korea.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: yksnbk@sm.ac.kr.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340, Republic of Korea. Electronic address: snkim@kist.re.kr.
authors.forename: Su-Nam
authors.initials: SN
authors.lastname: Kim
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D001483:Base Sequence; D016227:Benzoquinones / Q000494:pharmacology*; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000475:Alkenes; D016227:Benzoquinones; D017931:DNA Primers; D016328:NF-kappa B; D047493:PPAR alpha; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C528847:sargahydroquinoic acid
keywords: AP-1; MMPs; NF-κB; PPAR activator; Sargahydroquinoic acid