Dihydrocaffeic Acid Prevents UVB-Induced Oxidative Stress Leading to the Inhibition of Apoptosis and MMP-1 Expression via p38 Signaling Pathway.

Mariana M Oliveira,Tânia Ueda-Nakamura,Maria Da Conceição T Truiti,Bianca A Ratti,Rachel Auzély-Velty,Sueli O Silva,Regina G Daré,Celso V Nakamura

doi:10.1155/2019/2419096

Abstract

Chronic UVB exposure promotes oxidative stress, directly causes molecular damage, and induces aging-related signal transduction, leading to skin photoaging. Dihydrocaffeic acid (DHCA) is a phenolic compound with potential antioxidant capacity and is thus a promising compound for the prevention of UVB-induced skin photodamage. The aim of this study was to evaluate the antioxidant and protective effect of DHCA against oxidative stress, apoptosis, and matrix metalloproteinase (MMP) expression via the mitogen-activated protein kinase (MAPK) signaling pathway on L929 fibroblasts irradiated with UVB. DHCA exhibited high antioxidant capacity on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+), and xanthine/luminol/xanthine oxidase (XOD) assays and reduced UVB-induced cell death in the neutral red assay. DHCA also modulated oxidative stress by decreasing intracellular reactive oxygen species (ROS) and extracellular hydrogen peroxide (H2O2) production, enhancing catalase (CAT) and superoxide dismutase (SOD) activities and reduced glutathione (GSH) levels. Hence, cellular damage was attenuated by DHCA, including lipid peroxidation, apoptosis/necrosis and its markers (loss of mitochondria membrane potential, DNA condensation, and cleaved caspase 9 expression), and MMP-1 expression. Furthermore, DHCA reduced the phosphorylation of MAPK p38. These findings suggest that DHCA can be used in the development of skin care products to prevent UVB-induced skin damage.

Highlights

Ultraviolet (UV) irradiation is one of the major exogenous harmful agents to the skin
The ABTS+ scavenging ability of Dihydrocaffeic acid (DHCA) and QT was compared with a standard curve made with trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) solutions at different concentrations (5–250 μg/mL); the results were expressed as μM of trolox equivalent/μM of sample
The results of DHCA were compared with values obtained for QT, a flavonoid with high antioxidant potential described in the literature

Summary

Introduction

Ultraviolet (UV) irradiation is one of the major exogenous harmful agents to the skin. This irradiation consists of UVC (100–280 nm), UVB (280–320 nm), and UVA (320–400 nm), but only UVB and UVA reach the earth’s surface (95% UVA and 5% UVB). High levels of ROS induce matrix metalloproteinase-1 (MMP-1), MMP-3, and MMP-9 expression by triggering the phosphorylation of mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK. MAPKs induced by oxidative stress could mediate apoptosis in skin cells [6]. These sets of skin alterations generated by the oxidative

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