Zheng-wang Sun

Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice

Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin‐6, and MMP‐1 were significantly suppressed, and type I procollagen expression was stimulated in UVB‐irradiated and GA‐treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP‐1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor‐β1. Our data indicate that GA is a potential candidate for the prevention of UVB‐induced premature skin aging. Copyright

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.

Vigna angularis Water Extracts Protect Against Ultraviolet B-Exposed Skin Aging In Vitro and In Vivo

Exposure to ultraviolet (UV) radiation induces various pathological changes, such as thickened skin and wrinkle formation. In particular, UVB irradiation increases matrix metalloproteinase (MMP)-1 production and collagen degradation, leading to premature aging, termed photoaging. The azuki bean (Vigna angularis; VA) has been widely used as a food product as well as a traditional medicine. However, its activity needs additional study to confirm its functional application in foods and cosmetics for protecting skin. In this study, hot-water extract from VA (VAE) and its active component, rutin, were investigated to determine their antiphotoaging effects. VAE was found to have antioxidant activity. In UVB-exposed normal human dermal fibroblasts cells with VAE and rutin treatments, MMP-1 production was significantly suppressed (90% and 47%, respectively). The effects of both topical and oral administration of VAE were tested in UVB-irradiated hairless mice. VAE suppressed wrinkle formation and skin thickness by promoting elastin, procollagen type I, and TGF-β1 expression (118%, 156%, and 136%, respectively) and by diminishing MMP-1 production. These results suggest that VAE may be effective for preventing skin photoaging accelerated by UVB radiation.

Effects of Galla chinensis extracts on UVB-irradiated MMP-1 production in hairless mice

Galla chinensis (GAC) is a natural traditional Chinese medicine that has been widely used in folk medicine. Although GAC compounds (mainly gallic acid and methyl gallate) possess strong antiviral, antibacterial, anticancer, and antioxidant activities, there is no report regarding topical or oral administration of GAC compounds on UVB irradiation-induced photoaging in hairless mice (SKH: HR-1). In the present study, we examined cell viability, intracellular reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), and interleukin-6 (IL-6) in skin fibroblasts and keratinocytes induced by UVB in vitro. We also studied skin damage by measuring skin thickness, elasticity, wrinkling and levels of protein MMP-1, elastin, procollagen type I, and transforming growth factor-β1 (TGF-β1) in hairless mouse skin chronically irradiated by UVB in vivo. GAC treatment significantly prevented skin photoaging by reducing the levels of ROS, MMP-1, and IL-6 and promoting production of elastin, procollagen type I, and TGF-β1. According to the results of H&E staining and Masson’s trichrome staining, GAC reduced skin thickness and wrinkle formation while it increased skin elasticity. The effects of GAC on UVB-induced skin photoaging may be due to suppressed MMP-1 expression. These findings could be referenced for the development of new agents that target UVB-induced photoaging.

Enzyme-processed Korean Red Ginseng extracts protects against skin damage induced by UVB irradiation in hairless mice

UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-1 level, while accelerated procollagen type I, transforming growth factor-β1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes.

Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP‐1 and activation of Nrf2‐ARE antioxidant system

Solar ultraviolet (UV) radiation‐induced reactive oxidative species is mainly responsible for the development of photoageing. Rosmarinic acid was one of the main bioactive components detected in Thymus vulgaris (TV) we extracted. In this study, UVB‐induced skin damages have been shown to be ameliorated by treatment with TV in hairless mice (HR‐1) skin, demonstrated by decreased matrix metalloproteinases (MMPs) and increased collagen production. However, the underlying molecular mechanism on which TV acted was unclear. We examined the photoprotective effects of TV against UVB and elucidated the molecular mechanism in normal human dermal fibroblasts. Thymus vulgaris remarkably prevented the UVB‐induced reactive oxygen species and lactate dehydrogenase. Dose‐dependent increase in glutathione, NAD(P)H: quinone oxidoreductase1 and heme oxygenase‐1, by TV was confirmed by increased nuclear accumulation of Nrf2. Furthermore, 5‐Methoxyindole‐2‐carboxylic acid was introduced as a specific inhibitor of dihydrolipoyl dehydrogenase (DLD). We demonstrated that Nrf2 expression was regulated by DLD, which was a tricarboxylic acid cycle‐associated protein that decreased after UVB exposure. Besides, TV significantly diminished UVB induced phosphorylation of mitogen activated protein kinases pathway, containing extracellular signal‐regulated kinase, Jun N‐terminal kinase and p38, which consequently reduced phosphorylated c‐fos and c‐jun. Our results suggest that TV is a potential botanical agent for use against UV radiation‐induced oxidative stress mediated skin damages.

Dietary Foeniculum vulgare Mill extract attenuated UVB irradiation-induced skin photoaging by activating of Nrf2 and inhibiting MAPK pathways

BACKGROUND Foeniculum vulgare Mill (FV) has long been prescribed in traditional medicine due to its antioxidant anti-inflammatory properties. However, little research has been done on the use of FV to alleviate changes in UVB-induced photoaging PURPOSE: This study was to investigate the photoprotective effects and mechanism of FV in vitro and in vivo. METHODS The anti-photoaging effect of FV was assessed in normal human dermal fibroblasts (NHDFs) in vitro. The secretion of reactive oxygen species (ROS), lactate dehydrogenase (LDH), GSH, matrix metalloproteinases (MMPs), procollagen type I, IL-6 and transforming growth factor-β1 (TGF-β1) were measured by kits. Additionally, the level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), p-ERK and p38 were evaluated by western blotting. In vivo, H&E and Massons trichrome staining were employed. The expression of MMP-1, procollagen type I, TGF-β1 and elastin were measured by western blot. RESULTS FV significantly increased the production of collagen, elastin and TGF-β1 levels, while blocked matrix metalloproteinases (MMPs) production in UVB irradiation induced hairless mice, which were consistent with the result in NHDFs. Furthermore, FV dose-dependently decreased the production of ROS and LDH by promoting the nuclear amount of Nrf2 and enhancing the expression of cytoprotective antioxidants such as GSH. FV also significantly quenched UVB-induced phosphorylation of ERK and p38 in NHDFs. CONCLUSION Our results indicate that FV is a potential botanical agent for the treatment of skin damage induced by UV irradiation.

Methanol Extract of Bitter Melon Alleviates UVB‐Induced MMPs Expression via MAP Kinase and AP‐1 Signaling in Human Dermal Fibroblasts in vitro

Ultraviolet (UV) irradiation leads to photo‐damage of the skin, which in turn induces expression of matrix metalloproteinases (MMPs) and reduces type I procollagen. Bitter melon (Momordica charantia L.) has been widely used as a traditional medicine. In this study, we tested the photo‐protective effects of methanol extracts of bitter melon pulp (BM) and the mechanism of these effects in normal human dermal fibroblasts (NHDFs). The effects of BM were investigated by measuring the levels of MMP‐1, ‐3 and ‐9, and type I procollagen following UVB irradiation. We found that BM alleviates UVB‐induced MMP‐1, ‐3 and ‐9 expression at 100 µg/mL (down to 52.0%, 73.5%, and 55.6%, respectively). However, cells treated with 100 µg/mL BM had weakly stimulated type I procollagen expression (up to 130.0%). Moreover, treatment with BM significantly reduced 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. Therefore, our results suggest that BM is a potential agent for regulating skin photoaging. Copyright

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 1–100 μg/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.

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.