scholarly journals Propolis Suppresses UV-Induced Photoaging in Human Skin through Directly Targeting Phosphoinositide 3-Kinase

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3790
Author(s):  
Da Hyun Kim ◽  
Joong-Hyuck Auh ◽  
Jeongyeon Oh ◽  
Seungpyo Hong ◽  
Sungbin Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Skin ◽  
Therapeutic Potential ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Kinase Assay ◽  
Aging Effects ◽  
Propolis Extract ◽  
Pi3k Activity ◽  
Phosphoinositide 3 Kinase

Propolis is a resinous substance generated by bees using materials from various plant sources. It has been known to exhibit diverse bioactivities including anti-oxidative, anti-microbial, anti-inflammatory, and anti-cancer effects. However, the direct molecular target of propolis and its therapeutic potential against skin aging in humans is not fully understood. Herein, we investigated the effect of propolis on ultraviolet (UV)-mediated skin aging and its underlying molecular mechanism. Propolis suppressed UV-induced matrix metalloproteinase (MMP)-1 production in human dermal fibroblasts. More importantly, propolis treatment reduced UV-induced MMP-1 expression and blocked collagen degradation in human skin tissues, suggesting that the anti-skin-aging activity of propolis can be recapitulated in clinically relevant conditions. While propolis treatment did not display any noticeable effects against extracellular signal-regulated kinase (ERK), p38, and c-jun N-terminal kinase (JNK) pathways, propolis exerted significant inhibitory activity specifically against phosphorylations of phosphoinositide-dependent protein kinase-1 (PDK1) and protein kinase B (Akt). Kinase assay results demonstrated that propolis can directly suppress phosphoinositide 3-kinase (PI3K) activity, with preferential selectivity towards PI3K with p110α and p110δ catalytic subunits over other kinases. The content of active compounds was quantified, and among the compounds identified from the propolis extract, caffeic acid phenethyl ester, quercetin, and apigenin were shown to attenuate PI3K activity. These results demonstrate that propolis shows anti-skin-aging effects through direct inhibition of PI3K activity.

scholarly journals Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects

2020 ◽  
Vol 21 (22) ◽  
pp. 8439
Author(s):  
Kyung-Eun Lee ◽  
Sugyeong Jeong ◽  
Seok Kyun Yun ◽  
Seoyeon Kyung ◽  
Abadie Sophie ◽  
...  
Keyword(s):  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Biologically Active ◽  
Type I ◽  
Aging Effects ◽  
Type I Procollagen ◽  
Reproductive Axis ◽  
Stress Related Genes ◽  
Active Fragments ◽  
Aging Models

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.

scholarly journals Quercetin Directly Targets JAK2 and PKCδ and Prevents UV-Induced Photoaging in Human Skin

2019 ◽  
Vol 20 (21) ◽  
pp. 5262 ◽  
Author(s):  
Shin ◽  
Lee ◽  
Hong ◽  
Lim ◽  
Byun
Keyword(s):  
Protein Kinase ◽  
Human Skin ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Skin Aging ◽  
Janus Kinase ◽  
Activator Protein 1 ◽  
Protective Effects ◽  
Matrix Metalloproteinase 1 ◽  
Extracellular Signal

Quercetin is a naturally occurring polyphenol present in various fruits and vegetables. The bioactive properties of quercetin include anti-oxidative, anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the effect of quercetin on skin aging and the direct molecular targets responsible have remained largely unknown. Herein, we investigated the protective effect of quercetin against UV-mediated skin aging and the molecular mechanisms responsible. Treatment with quercetin suppressed UV-induced matrix metalloproteinase-1 (MMP-1) and cyclooxygenase-2 (COX-2) expression and prevented UV-mediated collagen degradation in human skin tissues. Quercetin exerted potent inhibitory effects towards UV-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activity. Further examination of the upstream signaling pathways revealed that quercetin can attenuate UV-mediated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N terminal kinases (JNK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Kinase assays using purified protein demonstrated that quercetin can directly inhibit protein kinase C delta (PKCδ) and Janus kinase 2 (JAK2) kinase activity. Quercetin was observed to bind to PKCδ and JAK2 in pull-down assays. These findings suggest that quercetin can directly target PKCδ and JAK2 in the skin to elicit protective effects against UV-mediated skin aging and inflammation. Our results highlight the potential use of quercetin as a natural agent for anti-skin aging applications.

scholarly journals Protein Kinase C-ζ Phosphorylates Insulin Receptor Substrate-1, -3, and -4 But Not -2: Isoform Specific Determinants of Specificity in Insulin Signaling

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2451-2458 ◽  
Author(s):  
Sihoon Lee ◽  
Edward G. Lynn ◽  
Jeong-a Kim ◽  
Michael J. Quon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Negative Feedback ◽  
Insulin Signaling ◽  
Kinase Assay ◽  
Insulin Receptor Substrate ◽  
Kinase C ◽  
Pi3k Activity ◽  
Pkc Ζ

Protein kinase C-ζ, a downstream effector of phosphatidylinositol 3-kinase (PI3K), phosphorylates insulin receptor substrate (IRS)-1 on serine residues impairing activation of PI3K in response to insulin. Because IRS-1 is upstream from PI3K, this represents a negative feedback mechanism that may contribute to signal specificity in insulin action. To determine whether similar feedback pathways exist for other IRS isoforms, we evaluated IRS-2, -3, and -4 as substrates for PKC-ζ. In an in vitro kinase assay, purified recombinant PKC-ζ phosphorylated IRS-1, -3 and -4 but not IRS-2. Similar results were obtained with an immune-complex kinase assay demonstrating that wild-type, but not kinase-deficient mutant PKC-ζ, phosphorylated IRS-1, -3, and -4 but not IRS-2. We evaluated functional consequences of serine phosphorylation of IRS isoforms by PKC-ζ in NIH-3T3IR cells cotransfected with epitope-tagged IRS proteins and either PKC-ζ or empty vector control. Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-ζ for IRS-1, -3, and -4 but not IRS-2. Significant insulin-stimulated increases in PI3K activity was coimmunoprecipitated with all IRS isoforms. In cells overexpressing PKC-ζ there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2. That is, PI3K activity associated with IRS-2 in response to insulin was similar in control cells and cells overexpressing PKC-ζ. We conclude that IRS-3 and -4 are novel substrates for PKC-ζ that may participate in a negative feedback pathway for insulin signaling similar to IRS-1. The inability of PKC-ζ to phosphorylate IRS-2 may help determine specific functional roles for IRS-2.

scholarly journals Exopolysaccharide from Lactobacillus plantarum HY7714 Protects against Skin Aging through Skin–Gut Axis Communication

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1651
Author(s):  
Kippeum Lee ◽  
Hyeon Ji Kim ◽  
Soo A Kim ◽  
Soo-Dong Park ◽  
Jae-Jung Shim ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Lactobacillus Plantarum ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Skin Damage ◽  
Genes Encoding ◽  
Natural Result

Skin aging occurs inevitably as a natural result of physiological changes over time. In particular, solar exposure of the skin accounts for up to 90% of skin damage. Numerous studies have examined the ability of dietary constituents to prevent skin aging, and recent research has emphasized the role of functional probiotics in intestinal function and skin aging. However, the mechanism of the interactions between aging and probiotics has not been elucidated yet. The aim of this study was to determine the role of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) identified as Lactobacillus plantarum HY7714 in regulating tight junctions in intestinal epithelial cells and increasing moisture retention in human dermal fibroblasts cells. We observed that HY7714 EPS controlled intestinal tight junctions in Caco-2 cells by upregulating the genes encoding occludin-1 (OCL-1) and zonula occluden-1 (ZO-1). In addition, HY7714 EPS effectively improved UVB-induced cytotoxicity and hydration capacity in HS68 cells by downregulating production of metalloproteinases (MMPs) and reactive oxygen species (ROS). In summary, HY7714 EPS is an effective anti-aging molecule in skin and may have therapeutic potential against skin diseases and UVB-induced damage. Therefore, HY7714 EPS serves as a functional substance in skin–gut axis communication.

scholarly journals Rapamycin Protects Skin Fibroblasts From UVA-Induced Photoaging by Inhibition of p53 and Phosphorylated HSP27

2021 ◽  
Vol 9 ◽  
Author(s):  
Gen-Long Bai ◽  
Ping Wang ◽  
Xin Huang ◽  
Zi-Yue Wang ◽  
Di Cao ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Aging Effects ◽  
Smad Signaling Pathway ◽  
Skin Photoaging ◽  
Dermal Collagen ◽  
Induced Apoptosis

Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.

scholarly journals The Antiaging Activity of Ergothioneine in UVA-Irradiated Human Dermal Fibroblasts via the Inhibition of the AP-1 Pathway and the Activation of Nrf2-Mediated Antioxidant Genes

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
You-Cheng Hseu ◽  
Yugandhar Vudhya Gowrisankar ◽  
Xuan-Zao Chen ◽  
Yi-Chen Yang ◽  
Hsin-Ling Yang
Keyword(s):  
Human Skin ◽  
Food Supplement ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Ros Generation ◽  
Human Skin Fibroblast ◽  
Type I ◽  
Dependent Manner ◽  
Protective Effects ◽  
Antioxidant Genes

UVA irradiation induced ROS-mediated photo damage to the human skin leading to coarseness, wrinkling, pigmentation, and cutaneous malignancies. We investigated the dermatoprotective efficacies of submicromolar concentrations of ergothioneine (EGT, 0.125-0.5 μM), which occurs naturally as a sulfur-containing amino acid, in the mechanisms in human skin fibroblast (HSF) cells. UVA-induced AP-1 (c-Fos and c-Jun) translocation was found to be inhibited by EGT treatments with the parallel inhibition of the collagenolytic matrix metalloproteinase- (MMP-) 1 activation and type I procollagen degradation. Moreover, EGT mitigated UVA-induced ROS generation. An increase in the amount of antioxidant genes (HO-1, NQO-1, and γ-GCLC) from EGT and were associated with upregulated Nrf2 expressions in a dose-dependent or time-dependent manner. We confirmed this from Nrf2 translocation and increased nuclear ARE promoter activity that underlie EGT dermatoprotective activities. Also, glutathione (GSH) levels (from γ-GCLC) were significantly increased. Moreover, we showed that mediated by ERK, JNK, and PKC, signaling cascades mediate Nrf2 translocation. We confirmed this phenomenon by the suppressed nuclear Nrf2 activation in cells that were treated with respective inhibitors (PD98059, SP600125, and GF109203X). However, antioxidant protein expressions were impaired in Nrf2 knockdown cells to confirm that ARE/Nrf2 pathways and the inhibition of AP-1 had significant roles in EGT-mediated protective effects. We can conclude that ergothioneine ameliorated UVA-induced skin aging and is a useful food supplement for skin care products.

scholarly journals Photoprotective and anti-skin-aging effects of eicosapentaenoic acid in human skin in vivo

2006 ◽  
Vol 47 (5) ◽  
pp. 921-930 ◽  
Author(s):  
Hyeon Ho Kim ◽  
Soyun Cho ◽  
Serah Lee ◽  
Kyu Han Kim ◽  
Kwang Hyun Cho ◽  
...  
Keyword(s):  
Eicosapentaenoic Acid ◽  
Human Skin ◽  
Skin Aging ◽  
Aging Effects

scholarly journals Characterization of Skin Aging–Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin

2015 ◽  
Vol 135 (8) ◽  
pp. 1954-1968 ◽  
Author(s):  
Daniel M. Waldera Lupa ◽  
Faiza Kalfalah ◽  
Kai Safferling ◽  
Petra Boukamp ◽  
Gereon Poschmann ◽  
...  
Keyword(s):  
Human Skin ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Secreted Proteins
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