Abstract
Citrus fruits contain various types of flavonoids with powerful anti-aging and photoprotective effects on the skin, and have thus been attracting attention as potential, efficacious skincare agents. Here, we aimed to investigate the chemical composition of Citrus unshiu and its protective effects on photoaging. We isolated and identified a bioactive compound, 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), from C. unshiu peels using ethanol extraction and hexane fractionation. HMF inhibited collagenase activity and increased type I procollagen content in UV-induced human dermal fibroblast neonatal (HDFn) cells. HMF also suppressed the expression of matrix metalloproteinases 1 (MMP-1) and induced the expression of type I procollagen protein in UV-induced HDFn cells. Additionally, HMF inhibited ultraviolet B (UVB)-induced phosphorylation of the mitogen-activated protein kinases (MAPK) cascade signaling components—ERK, JNK, and c-Jun—which are involved in the induction of MMP-1 expression. Furthermore, HMF affected the TGF-β/Smad signaling pathway, which is involved in the regulation of type I procollagen expression. In particular, HMF induced Smad3 protein expression and suppressed Smad7 protein expression in UV-induced HDFn cells in a dose-dependent manner. These findings suggest a role for Citrus unshiu in the preparation of skincare products in future.
Highlights
Skin aging, characterized by thickening, wrinkling, and roughness of the skin, is a complex process potentialing several aesthetic and functional changes
Chronic UV irradiation results in markedly increased reactive oxygen species (ROS) levels that trigger the release of proinflammatory cytokines and growth factors, and stimulate mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK), which converge to stimulate activator protein-1 (AP-1) [3,4,5]
The bioactive compound was identified as HMF by comparing its spectroscopic nuclear magnetic resonance (NMR) data with those previously reported in the literature (Figures 1A, S1 and S2, see Materials and Methods Section 3.2) [32,33,34]
Summary
Skin aging, characterized by thickening, wrinkling, and roughness of the skin, is a complex process potentialing several aesthetic and functional changes. It can be divided into two main processes: intrinsic (programmed) aging and photoaging. Photoaging, or photodamage, caused by exposure to ultraviolet (UV) radiation from the sun ( UVA (315–400 nm) and UVB radiation (280–315 nm) [1,2]), results in premature skin aging. The transcriptional activation of AP-1 increases the production of matrix metalloproteinases (MMPs), leading to degradation of the collagen and elastin fibers of the extracellular matrix which provide structural support to the skin dermis [8]. There are 23 known MMPs identified in humans, and AP-1 binding sites are found in the promoter region of several inducible human MMP genes, including
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