Malonic Acid Isolated from Pinus densiflora Inhibits UVB-Induced Oxidative Stress and Inflammation in HaCaT Keratinocytes.

Cheolwoo Park,Won-Jin Kim,Seok-Jun Kim,Hyeonsook Cheong,Jaeyoung Park,Woong Kim

doi:10.3390/polym13050816

Abstract

Skin aging is caused by exposure to various external factors. Ultraviolet B (UVB) irradiation induces oxidative stress, photoaging, and inflammation in skin cells. Pinus densiflora Sieb. et Zucc. (red pine) has various antimicrobial and antioxidant activities. However, the anti-inflammatory effects of red pine on skin have rarely been reported. The protective effects of malonic acid (MA) isolated from Pinus densiflora were investigated against UVB-induced damage in an immortalized human keratinocyte cell line (HaCaT). MA increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD-1) and heme oxygenase 1 (HO-1) via activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), resulting in a reduction in UVB-induced reactive oxygen species (ROS) levels. Additionally, the inhibition of ROS increased HaCaT cell survival rate. Thus, MA downregulated the expression of ROS-induced nuclear factor-κB, as well as inflammation-related cytokines (interleukin-6, cyclooxygenase-2, and tumor necrosis factor-α). Furthermore, MA significantly suppressed the mitogen-activated protein kinase/activator protein 1 signaling pathway and reduced the expression of matrix metalloproteinases (MMPs; MMP-1, MMP-3, and MMP-9). In contrast, MA treatment increased the expression of collagen synthesis regulatory genes (COL1A1 and COL3A1) via regulation of Smad2/3 signal induction through transforming growth factor-β. In conclusion, MA protected against UVB-induced photoaging via suppression of skin inflammation and induction of collagen biosynthesis.

Highlights

Skin aging is caused by exposure to various external factors, such as ultraviolet (UV) radiation, chemicals, and physical stimulation [1]
ultraviolet B (UVB)-induced reactive oxygen species (ROS) production triggers the expression of growth factor receptors, cell surface cytokines, and mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinase, which, in turn, regulate the activator protein 1 (AP-1) complex [7]
These data showed that malonic acid (MA) reduced UVB-induced ROS levels over time and inhibited ROS-mediated cell death in a dose-dependent manner

Summary

Introduction

Skin aging is caused by exposure to various external factors, such as ultraviolet (UV) radiation, chemicals, and physical stimulation [1]. Excessive exposure to ultraviolet B (UVB) radiation causes erythema, edema, sunburn, hyperplasia, inflammation, immunosuppression, skin photoaging, and photocarcinogenesis [2]. Upon acute exposure of the skin to UVB radiation, inflammatory responses to the degenerative processes are mediated primarily by the overproduction of intracellular reactive oxygen species (ROS) and damage to antioxidant defenses [3]. UVB-induced ROS production triggers the expression of growth factor receptors, cell surface cytokines, and mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinase, which, in turn, regulate the activator protein 1 (AP-1) complex [7]. MMPs play an important role in photocarcinogenesis by regulating various processes related to tumor progression, including tumor establishment, growth, metastasis, and angiogenesis [12]

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Conclusion