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 ◽  
...  

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.

Author(s):  
Gen-Long Bai ◽  
Ping Wang ◽  
Xin Huang ◽  
Zi-Yue Wang ◽  
Di Cao ◽  
...  

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.


1995 ◽  
Vol 108 (3) ◽  
pp. 1251-1261 ◽  
Author(s):  
R.A. Clark ◽  
L.D. Nielsen ◽  
M.P. Welch ◽  
J.M. McPherson

Transforming growth factor-beta, a potent modulator of cell function, induces fibroblasts cultured on plastic to increase collagen synthesis. In 5- and 7-day porcine skin wounds, which have minimal to moderate collagen matrix, respectively, transforming growth factor-beta and type I procollagen were coordinately expressed throughout the granulation tissue. However, in 10-day collagen-rich granulation tissue type I procollagen expression diminished despite persistence of transforming growth factor-beta. To investigate whether collagen matrix attenuates the collagen-synthetic response of fibroblasts to transforming growth factor-beta, we cultured human dermal fibroblasts in conditions that simulate collagen-rich granulation tissue. Therefore, human dermal fibroblasts were suspended in attached collagen gels and collagen and noncollagen production was assayed in the absence and presence of transforming growth factor-beta. Although transforming growth factor-beta stimulated collagen synthesis by fibroblasts cultured in the collagen gels, these fibroblasts consistently produced less collagen than similarly treated fibroblasts cultured on plastic. This phenomenon was not secondary to nonspecific binding of transforming growth factor-beta to the collagen matrix. Fibroblasts cultured in a fibrin gel responded to transforming growth factor-beta similarly to fibroblasts cultured on plastic. Using immunofluorescence probes to type I procollagen, we observed that transforming growth factor-beta increased type I procollagen expression in most fibroblasts cultured on plastic, but only in occasional fibroblasts cultured in collagen gels. From these data we conclude that collagen matrices attenuate the collagen synthetic response of fibroblast to transforming growth factor-beta in vitro and possibly in vivo.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3790
Author(s):  
Da Hyun Kim ◽  
Joong-Hyuck Auh ◽  
Jeongyeon Oh ◽  
Seungpyo Hong ◽  
Sungbin Choi ◽  
...  

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.


Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 432 ◽  
Author(s):  
Eugenie Mussard ◽  
Sundy Jousselin ◽  
Annabelle Cesaro ◽  
Brigitte Legrain ◽  
Eric Lespessailles ◽  
...  

Andrographis paniculata (Burm.f.) has long been used in ayurvedic medicine through its anti-inflammatory properties. However, its protective effect of skin aging has not been studied in vitro. This study aimed to investigate the anti-aging effects of methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12) on human dermal fibroblasts (HDFa) under pro-oxidant or pro-inflammatory condition. The in vitro anti-aging capacity of ME, ANDRO, NEO, 14DAP, and 14DAP11-12 (1, 2.5 and 5 µg/mL) was performed in HDFa. Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by the fluorescence of DCF-DA probe and cytokines were quantified by ELISA (IL6 and IL8) or RTqPCR (TNF-α). Procollagen type I production was determined by an ELISA. Our results showed a decrease in ROS production with ME and 14DAP at 5 µg/mL and 1 µg/mL, respectively. Furthermore, IL-6 production and TNF-α expression decreased under ANDRO and ME at 5 µg/mL. Our data indicated that ME and 14DAP protect from oxidative stress. Additionally, ME and ANDRO decreased an inflammation marker, IL-6. This suggests their potential natural treatment against skin damage. Hence, their applications could be of interest in cosmetics for preventing skin ageing.


2017 ◽  
Vol 45 (05) ◽  
pp. 1113-1124 ◽  
Author(s):  
Eunson Hwang ◽  
Hien T. T. Ngo ◽  
Bom Park ◽  
Seul-A Seo ◽  
Jung-Eun Yang ◽  
...  

Myrcene is an aromatic volatile compound that is commercially well-known as a flavor ingredient in the food industry and a fragrance in the soap and detergent industry. Given the worldwide interest in natural antiphotoaging products, we investigated the protective effects of myrcene in UVB-irradiated human dermal fibroblasts (NHDFs). NHDFs were subjected to 144[Formula: see text]mJ/cm2of UVB irradiation. The expression of intracellular reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), MMP-3, interleukin-6 (IL-6), transforming growth factor (TGF-[Formula: see text]1) and type I procollagen were examined. We showed that myrcene decreased the production of ROS, MMP-1, MMP-3, and IL-6, and increased TGF-[Formula: see text]1 and type I procollagen secretions. Furthermore, myrcene treatment (0.1–10[Formula: see text][Formula: see text]M) dramatically reduced the activation of MAPK-related signaling molecules such as p-ERK, p-p38, and p-JNK and AP-1 including p-c-Jun and p-c-Fos. Our data indicate that myrcene has a potential protective effect on UVB-induced human skin photoaging. Therefore, myrcene might have applications in the skincare industry.


Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 693
Author(s):  
Se-In Choi ◽  
Hee-Soo Han ◽  
Jae-Min Kim ◽  
Geonha Park ◽  
Young-Pyo Jang ◽  
...  

Chronic exposure to ultraviolet B (UVB) is a major cause of skin aging. The aim of the present study was to determine the photoprotective effect of a 30% ethanol extract of Eisenia bicyclis (Kjellman) Setchell (EEB) against UVB-induced skin aging. By treating human dermal fibroblasts (Hs68) with EEB after UVB irradiation, we found that EEB had a cytoprotective effect. EEB treatment significantly decreased UVB-induced matrix metalloproteinase-1 (MMP-1) production by suppressing the activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling and enhancing the protein expression of tissue inhibitors of metalloproteinases (TIMPs). EEB was also found to recover the UVB-induced degradation of pro-collagen by upregulating Smad signaling. Moreover, EEB increased the mRNA expression of filaggrin, involucrin, and loricrin in UVB-irradiated human epidermal keratinocytes (HaCaT). EEB decreased UVB-induced reactive oxygen species (ROS) generation by upregulating glutathione peroxidase 1 (GPx1) and heme oxygenase-1 (HO-1) expression via nuclear factor erythroid-2-related factor 2 (Nrf2) activation in Hs68 cells. In a UVB-induced HR-1 hairless mouse model, the oral administration of EEB mitigated photoaging lesions including wrinkle formation, skin thickness, and skin dryness by downregulating MMP-1 production and upregulating the expression of pro-collagen type I alpha 1 chain (pro-COL1A1). Collectively, our findings revealed that EEB prevents UVB-induced skin damage by regulating MMP-1 and pro-collagen type I production through MAPK/AP-1 and Smad pathways.


Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1609
Author(s):  
Hung Manh Phung ◽  
Sullim Lee ◽  
Sukyung Hong ◽  
Sojung Lee ◽  
Kiwon Jung ◽  
...  

Similar to other organs, the skin undergoes a natural aging process. Moreover, constant direct exposure to environmental stresses, including ultraviolet irradiation, causes the signs of skin aging to appear rather early. Reactive oxygen species (ROS) and inflammatory responses accelerate skin damage in extrinsic aging. In this study, we aimed to investigate the skin protective effects of polymethoxyflavones found in Kaempferia parviflora against oxidative stress and inflammation-induced damage in human dermal fibroblasts (HDFs) stimulated by tumor necrosis factor-α (TNF-α). The experimental data identified 5,7,4′ trimethoxyflavone (TMF) as the most potent constituent in preventing TNF-α-induced HDF damage among the tested compounds and it was not only effective in inhibiting matrix metalloproteinase-1 (MMP-1) production but also in stimulating collagen, type I, and alpha 1 (COLIA1) expression. TMF suppressed TNF-α-stimulated generation of ROS and pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), interleukin (IL)-1β, and IL-6 in HDFs. TMF also inhibited the pathways regulating fibroblast damage, including mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and nuclear factor-kappa B (NF-κB). In conclusion, TMF may be a potential agent for preventing skin aging and other dermatological disorders associated with oxidative stress and inflammation.


2019 ◽  
Vol 14 (8) ◽  
pp. 1934578X1987242
Author(s):  
Yumin Kim ◽  
Kyung Suk Bae

Ultraviolet radiation induces skin photoaging, which is associated with the elevation of matrix metalloproteinase-1 (MMP-1) and the decrease of procollagen. Nasturtium officinale plays a well-known role in the treatment of sulfur-containing compounds and their important role in protecting human health. However, their skin protective activity toward UVB-induced photodamage remains unclear. In the present study, we investigated the protective effect of indole 3-acetonitrile-4-methoxy-2- S-β-d-glucopyranoside (IAMG) from N. officinale on UVB-irradiated normal human dermal fibroblasts (NHDF). Our results show that IAMG enhanced NHDF cell migration. The UVB-induced increases in MMP-1 and decrease in type I procollagen were ameliorated by IAMG treatment. Taken together, our data strongly suggest that IAMG from N. officinale could reduce UVB-induced photodamage.


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