Protective Effect of Polymethoxyflavones Isolated from Kaempferia parviflora against TNF-α-Induced Human Dermal Fibroblast Damage

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.

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Andrographis paniculata and Its Bioactive Diterpenoids Protect Dermal Fibroblasts against Inflammation and Oxidative Stress

Antioxidants ◽

10.3390/antiox9050432 ◽

2020 ◽

Vol 9 (5) ◽

pp. 432 ◽

Cited By ~ 2

Author(s):

Eugenie Mussard ◽

Sundy Jousselin ◽

Annabelle Cesaro ◽

Brigitte Legrain ◽

Eric Lespessailles ◽

...

Keyword(s):

Oxidative Stress ◽

Dermal Fibroblasts ◽

Andrographis Paniculata ◽

Type I ◽

Ros Production ◽

Skin Damage ◽

Aging Effects ◽

Natural Treatment ◽

Tnf Α

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.

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Eisenia bicyclis Extract Repairs UVB-Induced Skin Photoaging In Vitro and In Vivo: Photoprotective Effects

Marine Drugs ◽

10.3390/md19120693 ◽

2021 ◽

Vol 19 (12) ◽

pp. 693

Author(s):

Se-In Choi ◽

Hee-Soo Han ◽

Jae-Min Kim ◽

Geonha Park ◽

Young-Pyo Jang ◽

...

Keyword(s):

Collagen Type ◽

Collagen Type I ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Tissue Inhibitors Of Metalloproteinases ◽

Epidermal Keratinocytes ◽

Heme Oxygenase 1 ◽

Type I ◽

Skin Damage ◽

Eisenia Bicyclis

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.

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(−)-Loliolide Isolated from Sargassum horneri Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation

Marine Drugs ◽

10.3390/md19080435 ◽

2021 ◽

Vol 19 (8) ◽

pp. 435

Author(s):

Ilekuttige Priyan Shanura Fernando ◽

Soo-Jin Heo ◽

Mawalle Kankanamge Hasitha Madhawa Dias ◽

Dissanayaka Mudiyanselage Dinesh Madusanka ◽

Eui-Jeong Han ◽

...

Keyword(s):

Inflammatory Responses ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Sargassum Horneri ◽

Mitogen Activated Protein Kinase ◽

Ros Generation ◽

Protective Effects ◽

Human Dermal Fibroblasts ◽

Mitogen Activated Protein ◽

Uvb Exposure

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC50 of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1β, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.

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Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

International Journal of Molecular Sciences ◽

10.3390/ijms21228693 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8693

Author(s):

Young Eun Choi ◽

Min Ji Song ◽

Mari Hara ◽

Kyoko Imanaka-Yoshida ◽

Dong Hun Lee ◽

...

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Transforming Growth Factor ◽

Mrna Level ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Cell Physiology ◽

Type I ◽

Tenascin C ◽

Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

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Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cell Culture Prevents UVB-Induced Skin Aging in Human Keratinocytes and Dermal Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms21010049 ◽

2019 ◽

Vol 21 (1) ◽

pp. 49 ◽

Cited By ~ 3

Author(s):

Lu Li ◽

Hien T.T. Ngo ◽

Eunson Hwang ◽

Xuan Wei ◽

Ying Liu ◽

...

Keyword(s):

Conditioned Medium ◽

Transforming Growth Factor ◽

Human Keratinocytes ◽

Transforming Growth Factor Β ◽

Antioxidant Response ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Heme Oxygenase 1 ◽

Type I ◽

Matrix Metalloproteinase 1

Human adipose-derived mesenchymal stem cells-conditioned medium (ADSC-CM) contains cytokines and growth factors that can facilitate the regeneration and repair of various tissues and organs. In the present study, the protective activity of ADSC-CM treatment was investigated in UVB-irradiated human keratinocyte cell line HaCaTs and normal human dermal fibroblasts (NHDFs). It was found that ADSC-CM can modulate the expression of the signaling molecules in the early UVB responsive signaling pathways, including mitogen activated protein kinases (MAPKs), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB). In addition, ADSC-CM treatment could upregulate antioxidant response element (ARE) such as phase II gene heme oxygenase-1 (HO-1) and increase the expression of collagen synthesis enhancer gene transforming growth factor-β (TGF-β). The expression of matrix metalloproteinase-1 (MMP-1) and procollagen type I synthesis inhibitors such as interleukin-6 (IL-6) was also found to be suppressed upon ADSC-CM treatment. Taken together, our study illustrates the anti-photoaging activities of ADSC-CM in cell-based models.

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Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging

10.20944/preprints202010.0572.v1 ◽

2020 ◽

Author(s):

Young Eun Choi ◽

Min Ji Song ◽

Mari Hara ◽

Kyoko Imanaka-Yoshida ◽

Dong Hun Lee ◽

...

Keyword(s):

Extracellular Matrix ◽

Type I Collagen ◽

Mrna Level ◽

Collagen Matrix ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Cell Physiology ◽

Type I ◽

Tenascin C ◽

Matrix Metalloproteinase 1

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

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The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Effects and Inflammatory Cytokines by 1α, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts

Cosmetics ◽

10.3390/cosmetics6030046 ◽

2019 ◽

Vol 6 (3) ◽

pp. 46 ◽

Cited By ~ 3

Author(s):

Neena Philips ◽

Xinxing Ding ◽

Pranathi Kandalai ◽

Ilonka Marte ◽

Hunter Krawczyk ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin D ◽

Oxidative Damage ◽

Inflammatory Cytokines ◽

Type I Collagen ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Type I ◽

Stress Effects ◽

Shock Proteins

Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation, are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1α, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. With regard to anti-inflammation, vitamin D inhibited expression of Il-1 and IL-8 in UVA-radiated fibroblasts, and stimulated HSP-70 in UVA-radiated and UVB-radiated fibroblasts. Overall, vitamin D is predominantly beneficial in preventing UVA-radiation induced photoaging through the differential regulation of the ECM, HSPs, and inflammatory cytokines, and protective effects on the cellular biomolecules. It is also beneficial in preventing UVB-radiation associated photoaging through the stimulation of cell viability and HSP-70, and the inhibition of cellular oxidative damage, and in preventing intrinsic aging through the stimulation of type I collagen and inhibition of cellular oxidative damage.

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Concentrated Growth Factor inhibit UVA-induced photoaging in Human Dermal Fibroblasts via the MAPK/AP-1 pathway

Bioscience Reports ◽

10.1042/bsr20193566 ◽

2020 ◽

Author(s):

Meng Zhang ◽

Tai Zhang ◽

Yanan Tang ◽

Guiyun Ren ◽

Yanning Zhang ◽

...

Keyword(s):

Growth Factor ◽

Uv Light ◽

Underlying Mechanism ◽

Protective Role ◽

Skin Aging ◽

Dermal Fibroblasts ◽

Mitogen Activated Protein Kinase ◽

Human Dermal Fibroblasts ◽

Matrix Metalloproteinase 1 ◽

Skin Photoaging

Ultraviolet (UV) radiation-induced photoaging is one of the contributors to skin aging. UV light triggers oxidative stress, producing a large number of matrix metalloproteinases and degrading the extracellular matrix in skin cells, thereby causing a series of photoaging symptoms. Concentrated growth factor (CGF) is a leukocyte- and platelet-rich fibrin biomaterial that plays a protective role in the occurrence and development of skin photoaging. In the present study, we investigated the underlying mechanism of CGF in the UVA-induced photoaging of human dermal fibroblasts (HDFs). A primary culture of HDFs was isolated from normal human facial skin. The cells were treated with CGF following UVA radiation. Proliferation of cells was detected using MTT assay, followed by measurement of reactive oxygen species (ROS) using immunofluorescence assay and flow cytometry. The mRNA and protein expression levels of P38, c-Jun, and matrix metalloproteinase-1 were detected using real-time polymerase chain reaction and western blot, respectively. CGF was found to improve cell viability by inhibiting the production of ROS and reducing oxidative damage. In addition, there was lower expression of p38 and c-Jun at the mRNA and protein levels following CGF treatment, thus resulting in the inhibition of MMP-1 expression. Our results suggest that CGF could protect HDFs against UVA-induced photoaging by blocking the P38 mitogen-activated protein kinase/activated protein-1 (P38MAPK/AP-1) signaling pathway. These findings provide a new clinical strategy for the prevention of skin photoaging.

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Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-α-Induced Damage of Human Dermal Fibroblasts

Antioxidants ◽

10.3390/antiox10040514 ◽

2021 ◽

Vol 10 (4) ◽

pp. 514

Author(s):

Sullim Lee ◽

Giang Do Hoang ◽

Daeyoung Kim ◽

Ho Sueb Song ◽

Sungyoul Choi ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Dermal Fibroblasts ◽

The Body ◽

Hazardous Substances ◽

Human Dermal Fibroblasts ◽

Cutaneous Lesions ◽

Matrix Metalloproteinase 1 ◽

Tnf Α ◽

Necrosis Factor

The skin is an important organ in the human body that protects the body from environmentally hazardous substances. Reactive oxygen species (ROS) cause inflammatory reactions and degradation of the extracellular matrix leading to skin aging and various cutaneous lesions. This study evaluated the potential of isoflavones isolated from Maclura tricuspidata fruit to prevent TNF-α-induced skin inflammation in normal human dermal fibroblasts (HDFs). It focused on alpinumisoflavone (AIF) that suppressed the accumulation of ROS and nitric oxide (NO) in tumor necrosis factor-alpha (TNF-α)-treated HDFs. AIF inhibited the TNF-α-induced increase in matrix metalloproteinase-1, decreased procollagen I α1, and suppressed pro-inflammatory mediators and pro-inflammatory cytokines, including NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8 that trigger inflammatory responses. AIF inhibited nuclear factor-κB and activating protein 1 mitogen-activated protein kinases that were increased by TNF-α stimulation. These results suggest that AIF may protect skin from aging and various cutaneous lesions.

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