1. Academic Validation
  2. Eupatilin with PPARα agonistic effects inhibits TNFα-induced MMP signaling in HaCaT cells

Eupatilin with PPARα agonistic effects inhibits TNFα-induced MMP signaling in HaCaT cells

  • Biochem Biophys Res Commun. 2017 Nov 4;493(1):220-226. doi: 10.1016/j.bbrc.2017.09.043.
Yujung Jung 1 Jin-Chul Kim 1 Yongsoo Choi 1 Sullim Lee 1 Ki Sung Kang 2 Yong Kee Kim 3 Su-Nam Kim 4
Affiliations

Affiliations

  • 1 Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea.
  • 2 College of Korean Medicine, Gachon University, Seongnam 461-701, Republic of Korea.
  • 3 College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
  • 4 Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea. Electronic address: snkim@kist.re.kr.
Abstract

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a flavonoid compound exhibiting several beneficial biological activities, including neuroprotection, anti-cancer, antinociception, chondroprotection, anti-oxidation, and anti-inflammation. Our previous study demonstrated that eupatilin specifically activates Peroxisome Proliferator-activated Receptor alpha (PPARα) through direct binding. The PPAR subfamily includes ligand-dependent transcription factors that consist of three isotypes: PPARα, PPARβ/δ, and PPARγ. All isotypes are involved in inflammation, epidermal proliferation/differentiation and skin barrier function. Among them, PPARα regulates lipid and glucose metabolism and skin homeostasis. In this study, we confirm that the ability of eupatilin as a PPARα Activator significantly inhibited tumor necrosis factor-alpha (TNFα)-induced matrix metalloproteinase (MMP)-2/-9 expression and proteolytic activity in HaCaT human epidermal keratinocytes. Furthermore, we found that eupatilin subsequently suppressed IκBα phosphorylation, blocked NF-κB p65 nuclear translocation and down-regulated MAPK/AP-1 signaling via PPARα activation. Taken together, our data suggest that eupatilin inhibits TNFα-induced MMP-2/-9 expression by suppressing NF-κB and MAPK⁄AP-1 pathways via PPARα. Our findings suggest the usefulness of eupatilin for preventing skin aging.

Keywords

AP-1; Eupatilin; MMPs; NF-κB; PPARα.

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