UVB-irradiated Normal Human Dermal Fibroblasts Research Articles

Protective effects of Carica papaya leaf against skin photodamage by blocking production of matrix metalloproteinases and collagen degradation in UVB-irradiated normal human dermal fibroblasts

Carica papaya is one of the most popular plants around the world. Various parts of Carica papaya have been used as ingredients in traditional medicine. However, no skin photoaging-related research has been performed with Carica papaya leaf (CPL). In the present study, Carica papaya leaf was investigated for its skin anti-aging effects in UVB-irradiated normal human dermal fibroblasts (NHDFs). Carica papaya leaf significantly suppressed UVB-induced activation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) signaling by scavenging reactive oxygen species (ROS) generation. Furthermore, our results indicated that CPL prevented degradation of Type I procollagen by positively modulating transforming growth factor-β1 (TGF-β1) activity and negatively regulating matrix metalloproteinases (MMPs) expression. Thus, the synthesis of Type I procollagen, a major component of extracellular matrix (ECM) was increased. In addition, a combination of both active compounds suggests they were active compounds of CPL. Taken together, the results suggest that Carica papaya leaf is promising for further investigation and development of a cosmetic product for the treatment of various skin conditions, including photoaging.

Protective Effects of Indole 3-Acetonitrile-4-Methoxy-2-S-β-d-Glucopyranoside From Nasturtium officinale R. Br. Against Ultraviolet B-Induced Photodamage in Normal Human Dermal Fibroblasts

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.

Protective Effects of C24 Ceramide From the Seeds of Brassica napus L. Against Ultraviolet B-Induced Photoaging in Normal Human Dermal Fibroblasts

Ultraviolet (UV) radiation induces skin photoaging, which is associated with the elevation of matrix metalloproteinase-1 (MMP-1) and the decrease of collagen. Brassica napus plays a well-known role in the treatment of canola oil through their anti-oxidative and DNA protective properties. However, their skin protective activity toward UVB-induced damage remains unclear. In the present study, we investigated the protective effect of C24 ceramide from B. napus on UVB-irradiated normal human dermal fibroblasts. Our results show that C24 ceramide enhanced NHDFs cell migration. The UVB-induced increase in MMP-1 and decrease in type I procollagen were ameliorated by C24 ceramide treatment. Taken together, our data strongly suggest that C24 ceramide from B. napus could reduce UVB-induced photoaging.

Evaluation of protective effect of cyclodextrin glucanotransferase-treated Gastrodia elata Blume extract on ultraviolet B-induced premature skin aging

Purpose: To investigate the protective effect of Gastrodia elata Blume (G. elata, GE) and cyclodextrin glucanotransferase (CGTase) enzyme-treated G. elata extract (EGE) against premature skin aging using ultraviolet B (UVB)-exposed normal human dermal fibroblasts (NHDFs).Methods: The extract was characterized by liquid chromatography with tandem mass spectrometry (LC-MS/MS), ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC–QToF–MS) and nuclear magnetic resonance spectroscopy (NMR). The expression of matrix metalloproteinases (MMP-1,3), interleukin-6 (IL-6), transforming growth factor (TGF-β1) and procollagen type I was assayed using ELISA kits. Safety evaluation of EGE’s dietary administration and topical application was performed by in vivo acute oral toxicity and local lymph node tests.Results: Lower MMP-1 and IL-6 and higher procollagen type I and TGF-β1 levels were observed after treatment with EGE than with GE, indicating that EGE was more effective than GE in treating UVBinduced photoaging. With respect to phenolic composition, EGE had lower 4-hydroxybenzaldehyde (4- HBA) level and higher α-gastrodin level than GE. In UVB-irradiated NHDFs, α-gastrodin exhibited higher anti-aging activity than 4-HBA and β-gastrodin based on the expression of MMP-1, MMP-3, and procollagen type I. The in vivo data indicate that EGE was safe at concentrations of up to 2000 mg/kg for dietary administration and 0.1 % for topical application.Conclusion: EGE protects UVB-induced photoaged human skin better than GE owing to its higher α- gastrodin content. Thus, EGE may be potentially useful agent in anti-aging cosmetic products.Keywords: Gastrodia elata, α-Gastrodin, Anti-aging, CGTase, Ultraviolet B (UVB) irradiation, Matrix metalloproteinase, Procollagen, Normal human dermal fibroblasts

Dietary enzyme-treated Hibiscus syriacus L. protects skin against chronic UVB-induced photoaging via enhancement of skin hydration and collagen synthesis

Exposure of skin to UVB radiation is associated with skin thickening, erythema, deep wrinkles, and marked losses of elasticity, resilience, and hydration. To find effective anti-aging materials, scientists have studied not only natural nutritional sources, but also biotransformed metabolites. Although Hibiscus syriacus L., the national flower of Korea has been used extensively throughout history, it has not yet been examined for possible anti-aging effects. In this study, skin anti-aging effects of H. syriacus L. water extract (HSL) and enzyme-treated H. syriacus L. extract (ETH) were investigated in normal human dermal fibroblasts (NHDFs) in vitro and in hairless mice in vivo. In UVB-irradiated NHDFs, higher level of type I procollagen and lower levels of matrix metalloproteinase-1 (MMP-1), mitogen-activated protein kinases (MAPKs), and activator protein-1 (AP-1) expression were identified after treatment with HSL and ETH. In photoaged hairless mice, skin thickening and the density of collagen fibers and filaggrin improved after oral administration of HSL and ETH. ETH 1% significantly inhibited melanin content, erythema index (EI), transepidermal water loss (TEWL), stratum corneum (SC) hydration, and wrinkle formation. Palmitic acid and linoleic acid were more abundant in ETH than in HSL. Taken together, both HSL and ETH protect skin from UVB-induced premature photoaging, and enzymatic biotransformed products like ETH have potential for use as valuable functional foods.

Prunella vulgaris L. Exerts a Protective Effect Against Extrinsic Aging Through NF-κB, MAPKs, AP-1, and TGF-β/Smad Signaling Pathways in UVB-Aged Normal Human Dermal Fibroblasts.

Prunella vulgaris L., a well-known traditional Chinese herbal medicine, has anti-inflammatory and antioxidant activities. In the present study, the underlying molecular mechanisms of the protective effect of P. vulgaris extract (PVE) were investigated in UVB-irradiated normal human dermal fibroblasts (NHDFs). The mRNA expression of matrix metalloproteinases (MMPs), procollagen type I, and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), was determined by reverse transcription–polymerase chain reaction. The expression of anti-photoaging-related signaling molecules in the NF-κB, MAPK/AP-1, and TGF/Smad pathways was assessed by western blot. We observed that PVE blocked the upregulated production of radical oxygen species induced in UVB-irradiated NHDFs in a dose-dependent manner. Treatment with PVE also significantly ameliorated the mRNA levels of MMPs, procollagen type I, TNF-α, and IL-6. In addition, the phosphorylation level of c-Jun and c-Fos was decreased through the attenuated expression levels of p-ERK and p-JNK after treatment with PVE. Furthermore, cells treated with PVE showed inhibited Smad 7 and increased Smad 2/3 expression in the TGF-β/Smad signaling pathway. Hence, synthesis of procollagen type I, a precursor of collagen I, was promoted. These findings indicate that treatment with PVE has a potential protective effect against UVB-induced photoaging and photoinflammation.

Orobanche cernua Loefling Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

UV radiation is the primary cause of skin photoaging, which results in an increase in matrix metalloproteinases and degradation of collagen. Developing new natural antioxidant as photoprotective agents has become a popular area of research. Orobanche cernua Loefling is a parasitic plant that is rich in phenylethanoid glycosides (PhGs). This study investigated the photoprotective effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its principal component acteoside on UVB-induced photoaging as well as their underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs). Biological testing demonstrated that OC and acteoside possessed significant photoprotective activities, reducing MMP and IL-6 levels while improving type-I procollagen synthesis in UVB-irradiated NHDFs. Further study showed that the protective mechanisms were the improvement of transcription factor Nrf2-mediated antioxidant defensive system, suppression of MAPK/AP-1 and activation of the TGF-β/Smad pathway. Together, our results suggested that OC might be a promising antiphotoaging agent against UV radiation-induced skin damage.

Antiphotoaging Effect of Prunus yeonesis Blossom Extract via Inhibition of MAPK/AP-1 and Regulation of the TGF-βI/Smad and Nrf2/ARE Signaling Pathways.

Cherry blossoms have attracted attention as an ingredient with potential for use in skincare products. However, no skin photoaging-related research has been performed with this plant. In this study, cherry blossom extract (CBE) at 1, 10 and 100 μg mL-1 was investigated for its skin antiphotoaging effects in UVB-irradiated normal human dermal fibroblasts (NHDF) cells in vitro. Our results showed that CBE markedly increased type-I procollagen during UVB exposure via two pathways. Firstly, transcription activator protein-1 expression and MAP kinases were downregulated, consequently reducing the production of matrix metalloproteinase (MMP)-1 and MMP-3. Secondly, transforming growth factor TGF-βI secretion was upregulated by Smads. Application of CBE facilitated the nuclear translocation of Nrf2 against reactive oxygen species (ROS)-induced damage, which is essential for the coordinated induction of cytoprotective enzymes. Together, our findings suggest that CBE may be a promising ingredient for skin aging therapy and provide a novel approach for alleviating cutaneous aging.

Borago officinalis L. attenuates UVB-induced skin photodamage via regulation of AP-1 and Nrf2/ARE pathway in normal human dermal fibroblasts and promotion of collagen synthesis in hairless mice

Ultraviolet B (UVB) irradiation is regarded as the main cause of skin photodamage. After exposure to UVB irradiation, collagen degradation is accelerated by upregulation of matrix metalloproteinases (MMPs), and collagen synthesis is decreased via downregulation of transforming growth factor (TGF)-β1 signaling. Borago officinalis L. (BO) is an annual herb with medicinal and culinary applications. Although BO has been demonstrated to have antioxidant and anti-inflammatory activities, its potential anti-photoaging effects have not been examined. In this study, we examined the protective effects of BO against skin photodamage in UVB-exposed normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. BO downregulated the expression of MMP-1, MMP-3, and IL-6, and enhanced TGF-β1 by modulating activator protein (AP-1) and nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling in UVB-irradiated NHDFs. We also found that dietary BO reduced wrinkle formation, epidermal thickness, and erythema in UVB-exposed skin. Moreover, skin hydration and collagen synthesis were improved by dietary BO treatment. Our results demonstrate that BO can be used in functional foods, cosmetic products, and medicines for prevention and treatment of UVB-induced skin photodamage.

Protective effect of dietary Alchemilla mollis on UVB-irradiated premature skin aging through regulation of transcription factor NFATc1 and Nrf2/ARE pathways

BackgroundAlchemilla mollis (lady's mantle) is a common ingredient in skin care products. However, the protective mechanism of A. mollis against skin problems has not been elucidated. PurposeThis study was to investigate the effects of A. mollis ethanolic extract (AM) on UVB-irradiated normal human dermal fibroblasts (NHDF) and hairless mice. MethodsThe in vitro anti-photoaging effect of AM was performed in NHDFs. The antioxidant activities were assessed through DPPH, ABTS, and reactive oxygen species (ROS) assays. Matrix metalloproteinase 1 (MMP-1), IL-6, procollagen type I, and transforming growth factor-β1 (TGF-β1) were measured by kits. The protein levels of p-c-Jun, p-c-Fos, Nrf2, NQO-1, HO-1, nuclear NFATc1 and cytosolic p-NFATc1 were evaluated by western blotting. In in vivo, H&E and Masson's trichrome staining were carried out. Skin texture was analyzed using the roughness parameters. The expression of MMP-1, procollagen type I, TGF-β1 and elastin were measured by western blot. ResultsAM included gallic acid as an active constituent. AM exhibited a strong antioxidant effect by inhibiting DPPH and ABTS free radicals, as well as ROS production. It was also found to upregulate transforming growth factor β1, type I procollagen and elastin expression, and to downregulate matrix metalloproteinase-1 and interleukin-6 expression in AM-treated NHDFs under UVB irradiation. These effects were attributed to AP-1 and Nrf2/ARE signaling pathways. Significantly, it was demonstrated that AM regulated the UVB-induced NFATc1 dephosphorylation in nucleus. Based on dietary data, AM was effective for the prevention of wrinkle formation, skin thickening, water loss, and erythema in UVB-exposed mouse skin. ConclusionOur data indicate that A. mollis provides protection from UVB exposure in both hairless mice skin in vivo and NHDFs in vitro. AM might therefore be useful as a cosmetic material and functional food for the prevention of UVB-induced human skin photoaging.

Angelica archangelia Prevented Collagen Degradation by Blocking Production of Matrix Metalloproteinases in UVB-exposed Dermal Fibroblasts.

Angelica archangelia (AA), a traditional herb, has attracted attention as an agent with potential for use in the prevention of chronic skin diseases. This study examined the photoprotective effects of AA on the inhibition of matrix metalloproteinases (MMPs) and collagen degradation in UVB-irradiated normal human dermal fibroblasts. Our results showed that AA markedly blocked collagen degradation by restraining the production of MMPs in UVB-exposed fibroblasts. We also investigated the underlying mechanism behind the effects of AA. AA attenuated UVB-triggered interleukin-6 (IL-6) and promoted the expression of transforming growth factor β1. Application of AA extract (10, 100 μg mL(-1) ) significantly diminished UVB-induced extracellular signal-regulated kinase and Jun-N-terminal kinase phosphorylation, which consequently reduced phosphorylated c-Fos and c-Jun. Our results indicated that AA inhibited the UVB-induced expression of MMPs by inhibiting mitogen-activated protein kinase signaling pathways and activator protein-1 activation. Our results suggest that AA is a promising botanical agent for use against skin photoaging.

Salvianolic Acid B Protects Normal Human Dermal Fibroblasts Against Ultraviolet B Irradiation-Induced Photoaging Through Mitogen-Activated Protein Kinase and Activator Protein-1 Pathways.

Exposure to ultraviolet (UV) light causes increased matrix metalloproteinase (MMP) activity and decreased collagen synthesis, leading to skin photoaging. Salvianolic acid B (SAB), a polyphenol, was extracted and purified from salvia miltiorrhiza. We assessed effects of SAB on UVB-induced photoaging and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts. Our results show that SAB significantly inhibited the UVB-induced expression of metalloproteinases-1 (MMP-1) and interleukin-6 (IL-6) while promoting the production of type I procollagen and transforming growth factor β1 (TGF-β1). Moreover, treatment with SAB in the range of 1-100μg/mL significantly inhibited UVB-induced extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 phosphorylation, which resulted in decreasing UVB-induced phosphorylation of c-Fos and c-Jun. These results indicate that SAB downregulates UV-induced MMP-1 expression by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathways and activator protein-1 (AP-1) activation. Our results suggest a potential use for SAB in skin photoprotection.

The Protective Effects of Fucosterol Against Skin Damage in UVB-Irradiated Human Dermal Fibroblasts

Exposure to ultraviolet (UV) light causes matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging. The activation of MMP is related to increased interlukin-6 (IL-6) and type I procollagen production, which is regulated by transforming growth factor-β1 (TGF-β1). Activator protein-1 (AP-1) activation induces MMP-1 production and reduces type I procollagen secretion. Fucosterol, which is extracted and purified from the brown algae Hizikia fusiformis, is a phytosterol. We assessed the effects of fucosterol on photodamage and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts by using enzyme-linked immunosorbent assay, Western blot analysis, and reverse transcription-polymerase chain reaction. Our results showed that fucosterol significantly decreased the UVB-induced expression of MMP-1, IL-6, p-c-Jun, and p-c-Fos. Additionally, fucosterol markedly increased the UVB-induced production of type I procollagen and TGF-β1. Our results indicate that fucosterol regulates MMP-1 and type I procollagen expression by modulating AP-1 and TGF-β1 signaling and that MMP-1 activation is correlated with IL-6. These data suggest that fucosterol is a promising botanical agent to protect against skin photodamage.

Titrated extract of Centella asiatica provides a UVB protective effect by altering microRNA expression profiles in human dermal fibroblasts

The titrated extract of Centella asiatica (TECA) is a reconstituted mixture comprising of asiatic acid, madecassic acid, asiaticoside and madecassoside, and is used as a therapeutic agent in wound healing and also as an anti-microbial, anticancer and anti-aging agent. Although these properties and the associated cell signaling pathways have been elucidated, the cellular mechanism of anti-photoaging upon ultraviolet (UV) exposure in normal human dermal fibroblasts (NHDFs) remains unknown. In this study, we investigated the photoprotective role of TECA via microRNA (miRNA) expression profiling analysis. Low dose of TECA did not exhibit toxicity and showed a protective effect against UVB irradiation in NDHFs. miRNA microarray experiments revealed that specific miRNAs were altered by TECA stimulation in UVB-irradiated NHDFs. Functional bioinformatic analysis showed that the putative target genes of the altered miRNAs were associated with the positive regulation of cell proliferation, anti-apoptosis, small GTPase- and Ras-mediated signal transduction and activation of MAPKK. Therefore, these results suggest that TECA may serve as a potential natural chemoprotective agent against UVB-mediated damage in NHDFs through changes in the expression of specific miRNAs.