2,4-Dihydroxyphenyl-benzo[d]thiazole (MHY553), a synthetic PPARα agonist, decreases age-associated inflammatory responses through PPARα activation and RS scavenging in the skin > REFERENCE LIBRARY

Highlights

MHY553 scavenges the reactive species (RS) radical.

MHY553 increases the transcriptional activity and expression of PPARα in aged skin and human fibroblasts.

MHY553 down-regulated the phosphorylation of MAP kinase signaling in aged skin and H₂O₂-induced fibroblasts.

MHY553 inhibited the NF-κB and AP-1 subunits in aged skin and H₂O₂-induced fibroblasts.

MHY553 was an activator of PPARα, which plays an important role in regulating the inflammatory response.

Abstract

We previously reported that 2,4-dihydroxyphenyl-benzo[d]thiazole (MHY553) is a PPARα agonist, which has been shown to inhibit tyrosinase activity in murine melanocyte and alleviate hepatic steatosis in aged rats. This study investigated the effects of MHY553 on the age-related occurrence of inflammatory responses via the molecular modulation of the nuclear factor-κB (NF-κB) signaling pathway in the skin of aged rats and skin fibroblast cells. Moreover, we investigated the antioxidant effect of MHY553 via in vitro assays of reactive oxygen species (ROS) and peroxynitrite (ONOO⁻) scavenging activities. We also scrutinized the ability of MHY553 as a PPARα activator in aged rat skin and H₂O₂-induced Hs27 fibroblast cells. In vivo experiments were performed in young, aged, and MHY553-fed aged rats (3 mg or 5 mg?kg ⁻¹?day ⁻¹ for 4 weeks). MHY553 dose-dependently scavenged ROS and ONOO⁻. Furthermore, we found that MHY553 suppressed the NF-κB transcription factor and downregulated mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling. MHY553 also inhibited the expression of pro-inflammatory cytokines including COX-2, iNOS, IL-1β, and IL-6. Our findings indicate the MHY553 scavenges ROS/reactive nitrogen species and inhibits inflammatory cytokines through PPARα activation in the skin. Thus, these results suggest that MHY553 may be of therapeutic interest for protecting skin from oxidative stress-induced damage and intrinsic aging.