The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging.

Hana Jung,Man-Ho Cho,Eunjoo Lee,Tae Lee

doi:10.3390/ijms17091449

Abstract

Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs), such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM) and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK) signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation.

Highlights

Skin aging can be characterized by two main processes, intrinsic and extrinsic aging
Our result showed that pretreatment with 20 μM of isosakuranetin suppressed the UV-B-induced matrix metalloproteinases (MMPs)-1 expression in HaCaT cells by 90% (Figure 4C), suggesting that it is a potent protective agent for the UV-mediated skin photo-damage
We examined the protective effect of diverse methoxyflavonoids on skin markers of photoaging using an in vitro model system and found that isosakuranetin inhibited Matrix Metalloproteinase-1 (MMP-1) expression and collagen degradation in UV-B-irradiated HaCaT and NHDF cells

Summary

Introduction

Skin aging can be characterized by two main processes, intrinsic and extrinsic aging. UV-A composing more than 90% of solar UV radiation can penetrate deep into the dermis and causes structural damage to the DNA, impairment of the immune system and skin cancer [3,4]. Chronic exposure of the skin to UV-B radiation results in activation of pro-inflammatory cytokines and inflammatory mediators, stimulation of the mitogen-activated protein kinase (MAPK) signaling pathway, and increased production of matrix metalloproteinases (MMPs), which cause alterations in the extracellular matrix (ECM) and accelerate skin aging [5,6,7]. Collagen degradation and inhibition of collagen synthesis deteriorate the structural integrity of the skin during photoaging [8,9,10,11]. Natural products possessing the ability to promote collagen synthesis or inhibit the major collagen-degradation enzymes are, possible to use as anti-photoaging cosmetic and therapeutic agents

Methods

Results

Conclusion