Piper retrofractum Vahl. Extract, as a PPARδ and AMPK Activator, Suppresses UVB-Induced Photoaging through Mitochondrial Biogenesis and MMPs Inhibition in Human Dermal Fibroblasts and Hairless Mice.

Jungon Yun,Jae-Kwan Hwang,Mi-Bo Kim,Changhee Kim

doi:10.1155/2018/6172954

Abstract

Photoaging occurs by UVB-irradiation and involves production of reactive oxygen species (ROS) and overexpression of matrix metalloproteinases (MMPs), leading to extracellular matrix damage. Piper retrofractum Vahl. is used as a traditional medicine for antiflatulence, expectorant, sedative, and anti-irritant; however, its antiphotoaging effect has not yet been studied. The current study investigated the antiphotoaging effect of standardized Piper retrofractum extract (PRE) on UVB-damaged human dermal fibroblasts and hairless mouse skin. PRE treatment activated the peroxisome proliferator-activated receptor delta (PPARδ) and the adenosine monophosphate-activated protein kinase (AMPK), consequently upregulating mitochondrial synthesis and reducing ROS production. Additionally, PRE inhibited MMPs expression via suppressing mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1). PRE downregulated UVB-induced inflammatory reactions by inhibiting the nuclear factor-kappa B (NF-κB) activity. PRE also enhanced transforming growth factor-beta (TGF-β) and the Smad signaling pathway, thereby promoting procollagen gene transcription. Furthermore, oral administration of PRE (300 mg/kg/day) similarly regulated the signaling pathways and increased antioxidant enzyme expression, thus attenuating physiological deformations, such as wrinkle formation and erythema response. Collectively, these results suggest that PRE acts as a potent antiphotoaging agent via PPARδ and AMPK activation.

Highlights

Skin aging is divided into intrinsic aging and extrinsic aging
In order to confirm the mitochondrial biogenesis by Piper retrofractum extract (PRE), we evaluated the Relative luciferase activity (% of control)
UVBirradiation induced the expression of inflammatory factors, such as NF-κB, IL-1β, IL-6, and IL-8, whereas PRE treatment inhibited their expression levels (Figures 2(c) and 2(d)). These results indicate that PRE inhibits the expression of matrix metalloproteinases (MMPs) by suppressing the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) pathways and protects the skin from UVB-induced inflammation by attenuating NF-κB expression

Summary

Introduction

Skin aging is divided into intrinsic aging and extrinsic aging. Intrinsic aging results from physiological changes that occur over time [1]. Extrinsic aging is caused by external factors such as chemicals, stress, physical stimulation, or ultraviolet radiation [2]. Mitochondria are organelles that regulate ATP biosynthesis and cell apoptosis [4]. UVB disrupts the mitochondrial electron transport system, resulting in mitochondrial dysfunction and apoptosis [6]. Maintenance of the number of mitochondria can delay the development of skin photoaging. Mitochondrial biogenesis, a process to form new mitochondria, is regulated by peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (Tfam) [7]. Increasing the number of mitochondria by upregulating these genes can be a way to prevent skin photoaging

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Conclusion