Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

Shin, Mi Hee; Lee, Se Rah; Kim, Min Kyoung; Shin, Changyong; Lee, Dong Hun; Chung, Jin Ho

doi:10.1371/journal.pone.0162628

Cited by 36 publications

(26 citation statements)

References 49 publications

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“…We believe targeting PPAR α to be important in targeting conspicuous pores and age spots as levels of its mRNA are diminished in photodamaged skin . Moreover, its levels were diminished in irradiated fibroblasts.…”

Section: Discussionmentioning

confidence: 93%

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Schütz

Rawlings²,

Wandeler

et al. 2019

Intern J of Cosmetic Sci

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IntroductionWe report on the preparation and efficacy of 10‐hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores.MethodsThe hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm−2) by immunohistochemistry on human ex vivo skin. UVB‐induced expression of matrix metalloprotease‐1 (MMP‐1) was determined from full thickness skin by RT‐qPCR. Modification of the fibroblast secretome by HSA was studied by mass‐spectrometry‐based proteomics. In a full‐face, double blind, vehicle‐controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8‐week period.ResultsHSA was obtained in enantiomeric pure, high yield (≥80%). Collagen type I and type III levels were dose‐dependently increased (96% and 244%; P < 0.01) in vitro and collagen type III in ex vivo skin by +57% (P < 0.01) by HSA. HSA also inhibited UVB‐induced MMP‐1 gene expression (83%; P < 0.01) and mitigated SBC induction (−34% vs. vehicle control) and reduced significantly UV‐induced p53 up‐regulation (−46% vs. vehicle control; P < 0.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies in silico and EC50 determination in reporter gene assays (EC50 5.5 × 10−6 M) identified HSA as a peroxisomal proliferator activated receptor‐α (PPARα) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (P < 0.05) after 8 weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, P < 0.05) after 4 weeks.ConclusionHSA acts as a PPARα agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP‐1 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.

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Section: Discussionmentioning

confidence: 93%

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Schütz

Rawlings²,

Wandeler

et al. 2019

Intern J of Cosmetic Sci

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“…Catalase cleaves hydrogen peroxide to oxygen and water . Catalase overexpression in keratinocytes reduces apoptosis and MMP‐1 expression . GSH reduces hydrogen peroxide and lipid radicals formed during oxidative stress, contributing to reduction of the MMP‐1 level that is enhanced by UV‐B irradiation .…”

Section: Discussionmentioning

confidence: 99%

“…28 Catalase overexpression in keratinocytes reduces apoptosis and MMP-1 expression. 29,30 GSH reduces hydrogen peroxide and lipid radicals formed during oxidative stress, contributing to reduction of the MMP-1 level that is enhanced by UV-B irradiation. 31,32 We found that UV-B exposure significantly reduced both GSH and catalase levels;…”

Section: Bbe Inhibits Uv-b-induced Ros Generation In Keratinocytesmentioning

confidence: 99%

Protective effects of Belamcandae Rhizoma against skin damage by ameliorating ultraviolet‐B‐induced apoptosis and collagen degradation in keratinocytes

Noh

Choi

Lee

et al. 2019

Environmental Toxicology

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Ultraviolet‐B light (UV‐B) is a major cause of skin photoaging, inducing cell death and extracellular matrix collapse by generating reactive oxygen species (ROS). Belamcandae Rhizoma (BR), the rhizome of Belamcanda chinensis Leman, exhibits antioxidant properties, but it remains unknown whether BR extract ameliorates UV‐B‐induced skin damage. In this study, we evaluated the effects of a standardized BR extract on UV‐B‐induced apoptosis and collagen degradation in HaCaT cells. BR was extracted using four different methods. We used radical‐scavenging assays to compare the antioxidative activities of the four extracts. Cells were irradiated with UV‐B and treated with BR boiled in 70% (vol/vol) ethanol (BBE). We measured cell viability, intracellular ROS levels, the expression levels of antioxidative enzymes, and apoptosis‐related and collagen degradation‐related proteins. The irisflorentin and tectorigenin levels were measured via high‐performance liquid chromatography. BBE exhibited the best radical‐scavenging and cell protective effects of the four BR extracts. BBE inhibited intracellular ROS generation and induced the synthesis of antioxidative enzymes such as catalase and glutathione. BBE attenuated apoptosis by reducing the level of caspase‐3 and increasing the Bcl‐2/Bax ratio. BBE reduced the level of matrix metalloproteinase‐1 and increased that of type I collagen. The irisflorentin and tectorigenin contents were 0.23% and 0.015%, respectively. From these results, BBE ameliorated UV‐B‐induced apoptosis and collagen degradation by enhancing the expression of antioxidative enzymes. It may be a useful treatment for UV‐B‐induced skin damage.

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“…Catalase breaks down hydrogen peroxide, rendering it nontoxic [17]. The overexpression of catalase was shown to protect keratinocytes by decreasing intracellular ROS, inhibiting apoptosis in keratinocytes [18], and reducing MMP-1 levels in dermal fibroblasts [19]. GSH reduces oxidative molecules, including hydrogen peroxides and lipid radicals, by acting as an electron donor, which results in its conversion to GSSG.…”

Section: Discussionmentioning

confidence: 99%

Tectorigenin, a Flavonoid-Based Compound of Leopard Lily Rhizome, Attenuates UV-B-Induced Apoptosis and Collagen Degradation by Inhibiting Oxidative Stress in Human Keratinocytes

et al. 2018

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Ultraviolet (UV) light, a major risk factor for external skin photoaging, induces oxidative stress in skin. UV causes a breakdown of skin homeostasis by impairing the extracellular matrix and inducing cell death. Tectorigenin, a constituent of leopard lily (Belamcanda chinensis L.) rhizome, has been reported to possess antioxidant, hair-darkening, and anti-inflammatory activities; however, the effect of tectorigenin on UV-B-induced skin damage is unknown. Here, we investigated the anti-skin-damage effects of tectorigenin against UV-B-stimulated oxidative stress in human keratinocytes. We irradiated HaCaT cells with UV-B (25 mJ/cm2), followed by treatment with tectorigenin for 24 h. We found that tectorigenin decreased the levels of intracellular reactive oxygen species by increasing the expression of anti-oxidative enzymes, such as glutathione and catalase. Furthermore, tectorigenin inhibited apoptosis by reducing caspase-3- and Bcl-2-associated protein-X levels, and increasing Bcl-2 protein levels. Tectorigenin also decreased matrix metalloproteinase-1 levels and increased type 1 collagen levels, thus preventing collagen degradation. These data demonstrate that tectorigenin exerts anti-skin-damage effects in human keratinocytes by attenuating UV-B-induced hyper-oxidation, apoptosis, and collagen degradation.

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Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

Cited by 36 publications

References 49 publications

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Protective effects of Belamcandae Rhizoma against skin damage by ameliorating ultraviolet‐B‐induced apoptosis and collagen degradation in keratinocytes

Tectorigenin, a Flavonoid-Based Compound of Leopard Lily Rhizome, Attenuates UV-B-Induced Apoptosis and Collagen Degradation by Inhibiting Oxidative Stress in Human Keratinocytes

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