UVB-induced Activation Research Articles

Chikusetsusaponin IVa from Dolichos lablab Linne attenuates UVB-induced skin photoaging in mice by suppressing MAPK/AP-1 signaling

Ultraviolet-B (UVB) radiation-induced photoaging of the skin is characterized by amplified expression of matrix metalloproteinase-1 (MMP-1) and reduced collagen fibers, both of which contribute to skin wrinkle formation. Edible natural products can protect against skin photoaging. Here, we investigate the protective effect of Dolichos lablab Linne (DLL) water extract against UVB radiation-prompted skin damage and attempt to uncover its fundamental mechanisms in human keratinocytes (HaCaT) and HR-1 hairless mouse. We found DLL extract rescued the reduction in cell viability associated with UVB exposure without any associated cytotoxic effects. It also protected against skin photoaging by inhibiting mitogen-activating protein kinase (MAPK) signaling, thereby preventing the UVB-associated increase in MMP-1 and -9 expression. DLL extract also increased the expression of both superoxide dismutase 1 (SOD1) and catalase (CAT). We identified chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A as bioactive components of DLL. Although we have not yet identified the mechanisms by which these compounds reduce the effects of photoaging, we have demonstrated that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce MMP-1, MMP-9, p–c-Fos, and p–c-Jun expression, while also avoiding any cytotoxicity. We found oral administration of DLL extract effectively alleviated dorsal epidermal thickening and skin dehydration in HR-1 hairless mouse visible to UVB. DLL extract also prevents UVB-induced activation of the MAPK/AP-1 signaling pathway, thereby reducing the expression of MMPs in dorsal mouse skin. Our results indicate that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A are bioavailable components of DLL extract that can reduce UVB-induced skin damage via MMPs by deactivating the MAPK/AP-1 signaling pathway. These findings suggest DLL extract can be used as a skin anti-photoaging agent.

Actinidia chinensis Planch Ameliorates Photoaging in UVB-Irradiated NIH-3T3 Cells and SKH-1 Hairless Mice by Controlling the Reactive Oxygen Species/AKT Pathway.

In this study, we evaluated the antiphotoaging properties of Actinidia chinensis Planch (ACP) and the molecular mechanisms underlying its ability to prevent UVB-mediated photoaging. Administration of the ethanolic extract of ACP (EEACP) to the dorsal area of hairless mice effectively ameliorated UVB-mediated wrinkle formation, epidermal thickening, and loss of lipid droplets in the epidermis. Additionally, the UVB-induced loss of collagen content in the epidermis was significantly attenuated in mouse skin treated with EEACP. The expression of procollagen type 1 and metalloproteinase-1a, which are related to collagen content in the epidermis, was restored by EEACP treatment in UVB-irradiated mice and NIH-3T3 mouse skin fibroblast cells. Interestingly, EEACP effectively ameliorated UVB-induced reactive oxygen species overproduction. Furthermore, the activation/phosphorylation of AKT, rather than mitogen-activated protein kinases, has been identified as a major target of EEACP in preventing UVB-mediated photoaging. Additionally, N-(1 deoxy-1-fructosyl) valine and phenethylamine glucuronide were identified as analytical indicators of EEACP using high-performance liquid chromatography/mass spectrometry. These results suggest that EEACP can be developed as a functional natural agent capable of preventing photoaging by attenuating UVB-induced activation of the reactive oxygen species/AKT pathway.

Oleracone C from Portulaca oleracea attenuates UVB-induced changes in matrix metalloproteinase and type I procollagen production via MAPK and TGF-β/Smad pathways in human keratinocytes.

Chronic exposure to ultraviolet (UV) radiation induces photo-oxidation, which in turn causes the overproduction of matrix metalloproteinases (MMPs) and collagen degradation. These symptoms are referred to as photoaging, which is characterized by skin thickness, irregular pigmentation, elastosis and coarse wrinkles. In this study, the protective effects of oleracone C isolated from Portulaca olerace against UVB-induced changes in MMPs and type I procollagen production were investigated in human keratinocytes. Human immortalized keratinocytes have been used as an in vitro cell model to study the abnormal skin barrier development such as in photoaging. The effects of the compound on cell viability were determined by colorimetric MTT assay. This study also measured ROS production using DCFH-DA assay. Releases of MMPs and type Iα1 procollagen were analysed by ELISA. RT-PCR and Western blot were carried out to test the expressions of mRNA and proteins related to MMPs and type I procollagen biosynthesis. Effect of oleracone C against UVB-mediated oxidative stress was evaluated measuring its ability to eliminate UVB-induced activation of reactive oxygen species (ROS). Treatment of oleracone C hindered the production of intracellular ROS. UVB exposure increased MMPs (MMP-1, MMP-2 and MMP-9) release from keratinocytes and decreased the release of type I procollagen. Treatment with oleracone C reversed these effects of UVB exposure. Oleracone C treatment also diminished the intracellular expression of MMP-1, MMP-2 and MMP-9 and elevated the type I procollagen. Oleracone C suppressed the UVB irradiation-dependent upregulation phosphorylation of p38 and ERK1/2 in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, oleracone C stimulated collagen production through the TGF-β signalling pathway, which activates collagen synthesis in UVB-irradiated keratinocytes. These findings reasonably suggest ameliorating the potential of oleracone C against the UVB-induced photoaging of the human keratinocytes.

Jelly Fig (Ficus awkeotsang Makino) Exhibits Antioxidative and Anti-Inflammatory Activities by Regulating Reactive Oxygen Species Production via NFκB Signaling Pathway.

Antioxidant and anti-inflammatory activities of Ficus awkeotsang Makino extract (FAE) on Hs68 fibroblasts and BALB/c nude-mouse models are evaluated in this study. FAE was found to be non-toxic and showed high levels of DPPH, H2O2, and hydroxyl radical scavenging abilities; a ferrous chelating capacity; as well as ferric-reducing antioxidant capability. The antioxidant activity of FAE was strongly associated with polyphenolic content (flavonoids at 10.3 mg QE g−1 and total phenol at 107.6 mg GAE g−1). The anti-inflammatory activity of FAE and the underlying molecular mechanisms were also investigated. The a* value of the mouse dorsal skin after treatment with FAE at 1.5 mg/mL in addition to chronic UVB exposure was found to decrease by 19.2% during a ten-week period. The anti-inflammatory effect of FAE was evidenced by the decreased accumulation of inflammatory cells and skin thickness. Expression levels of UVB-induced inflammatory proteins, including ROS, NF-κB, iNOS, COX-2, and IL-6, were significantly reduced upon FAE treatment in vitro and in vivo. Collectively, our results suggest that the inhibition of ROS and UVB-induced activation of the NF-κB downstream signaling pathway by FAE, indicating considerable potential as a versatile adjuvant against free radical damage in pharmaceutical applications.

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

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.

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.

UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

Effects of Time on Phenolics and in vitro Bioactivity in Autoclave Extraction of Graviola (Annona muricata) Leaf

We investigated the effects of different autoclave extraction times (1-6 h) on the antioxidant, antidiabetic, and anti-inflammatory activities of phenolic compounds isolated from graviola (Annona muricata) leaves. In terms of yield and content of total polyphenols, total flavonoids, rutin, and kaempferol-3-O-rutinoside, the optimal extraction time was 4 h. At this time point, water extracts from graviola leaves (WEG) exhibited the highest DPPH radical scavenging activity, ferric reducing antioxidant power, and α-glucosidase inhibitory activity. The α-glucosidase inhibitory activity of WEG was significantly stronger than that of acarbose. Furthermore, WEG significantly suppressed lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells and inhibited UVB-induced activator protein-1 (AP-1)-dependent transcription in human keratinocytes. In conclusion, WEG can be used as functional food ingredients in the food industry.

Antiphotoaging Effects of 3,5-Dicaffeoyl-epi-quinic Acid via Inhibition of Matrix Metalloproteinases in UVB-Irradiated Human Keratinocytes.

UVB exposure is one of the causes of several skin complications including but not limited to premature aging, wrinkle formation, and hyperpigmentation. UV-induced skin aging is called photoaging, and oxidative stress-induced overexpression of matrix metalloproteinases (MMPs) is the main reason behind the photoaging-mediated collagen degradation. Natural origin inhibitors of MMPs are regarded as a promising approach to prevent or treat photoaging. Therefore, the present study investigated the protective effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA) in human HaCaT keratinocytes against UVB irradiation-related dysregulation of MMPs. Changes in the mRNA and protein expression and release of MMP-1, -2, and -9 were observed after UVB irradiation with or without DCEQA treatment. In addition, the effect of DCEQA on the activation of p38, JNK, and ERK MAPKs was analyzed. Treatment of UVB-irradiated HaCaT cells with 10 μM DCEQA significantly suppressed the overexpression of both mRNA and protein of MMP-1, -2, and -9 while slightly increasing the diminished type I procollagen production. UVB-induced activation of MAPKs was also ameliorated by DCEQA treatment in a dose-dependent manner. Results indicated that DCEQA treatment was able to protect keratinocytes from UVB-induced photoaging by inhibiting the stimulated production of MMPs and the related decrease in collagen production. It was suggested that DCEQA downregulated the collagen degradation via inhibition of MAPK activation, which resulted in decreased MMP activity.

Protective effects of Oxya chinensis sinuosa Mishchenko against ultraviolet B-induced photodamage in hairless mice

BackgroundEdible insects, including Oxya chinensis sinuosa Mishchenko (Oc), which is consumed as food in Asia, are considered as a human food shortage alternative, and also as a preventive measure against environmental destruction. Ultraviolet B (UVB) irradiation, which causes skin photodamage, is considered as an extrinsic skin aging factor. It reduces skin hydration, and increases wrinkle formation and reactive oxygen species (ROS) and inflammatory cytokine expression. Thus, the objective of this study was to investigate the anti-aging effects of an ethanol extract of Oc (Oc.Ex).MethodsA UVB-irradiated hairless mouse model was used to examine relevant changes in skin hydration, wrinkle formation, and skin epidermal thickness. Also, antioxidant markers such as superoxide dismutase (SOD) and catalase (CAT) were analyzed, and Oc. Ex skin protective effects against UVB irradiation-induced photoaging were examined by determining the levels of skin hydration factors.ResultsOc.Ex improved epidermal barrier dysfunctions such as increased transepidermal water loss (TEWL) and capacitance reduction in UVB-irradiated mice. It upregulated skin hydration-related markers, including hyaluronic acid (HA), transforming growth factor (TGF)-β, and pro-collagen, in UVB-irradiated mice, compared with the vehicle control group. It also reduced UVB-induced wrinkle formation, collagen degradation, and epidermal thickness. Additionally, it remarkably suppressed the increased expression of matrix metalloproteinases (MMPs), and restored the activity of SOD and CAT in UVB-irradiated mice, compared with the vehicle control group. Furthermore, Oc. Ex treatment downregulated the production of inflammatory cytokines and phosphorylation of the mitogen-activated protein kinases (MAPKs) signaling pathway activated by UVB irradiation.ConclusionThis study revealed that Oc. Ex reduced skin thickness and the degradation of collagen fibers by increasing hydration markers and collagen-regulating factors in the skin of UVB-irradiated mice. It also inhibited UVB-induced antioxidant enzyme activity and inflammatory cytokine expression via MAPK signaling downregulation, suggesting that it prevents UVB-induced skin damage and photoaging, and has potential for clinical development in skin disease treatment.

Red Raspberry Extract Protects the Skin against UVB-Induced Damage with Antioxidative and Anti-inflammatory Properties

Extensive exposure to UVB (280–320 nm) is the major risk responsible for various skin injuries. Numerous reports have shown that natural products could demonstrate photochemopreventive efficacy against UVB damage. We investigated the preventive effects and associated molecular mechanisms of red raspberry extract upon UVB-caused damage in human epidermal keratinocytes and a nude mouse model. The protein profiles and immunohistological study on a nude mouse skin indicated that red raspberry extract could prevent UVB-caused cell death and protect the skin against UVB-exposed injury manifested by wrinkling, scaling, tanning, and water loss as well as epidermal thickening. In addition, red raspberry extract application effectively abolished oxidative damage in DNA and attenuated the carbonylation level of proteins, which attributed to the activation of SOD, Nrf2 and its target genes, and HO-1. Red raspberry extract also altered the cells' apoptotic signaling pathways including caspase-3 as well as the inflammatory cascade such as c-jun and attenuated UVB-induced activation of NF-κB and COX-2. Red raspberry extract could alleviate direct photodamage to the skin caused by UVB exposure through the ROS scavenger and protection against inflammatory responses, which may allow the development of novel strategies in protecting the skin subjected to UVB radiation.

Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

Ultraviolet radiation is markedly increased because of pollution and the depletion of the stratospheric ozone layer. Excessive exposure to sunlight can negatively affect the skin, resulting in sunburn, photo-aging, or skin cancer. In this study, we first determined the photoprotective effect of sanshool, a major component in Zanthoxylum bungeanum, on UVB-irradiated responses in human dermal fibroblasts (HDFs) and nude mouse. We found that sanshool treatment can protect cells against the effects of UVB irradiation by (i) increasing cell viability, (ii) inhibiting MMP expression, and (iii) inducing autophagy. We also used the recombinant CSF2 or anti-CSF2 antibody co-cultured with human dermal fibroblasts (HDFs) and found that CSF2 contributes to sanshool-induced autophagy. Sanshool hindered the UVB-induced activation of JAK2-STAT3 signaling in HDFs, thereby inhibiting the expression of MMPs and activation of autophagic flux. Exposure of the dorsal skin of hairless mice to UVB radiation and subsequent topical application of sanshool delayed the progression of skin inflammation, leading to autophagy and inhibiting the activation of JAK2-STAT3 signaling. These results provide a basis for the study of the photoprotective effect of sanshool and suggest that it can be potentially used as an agent against UVB-induced skin damage in humans.

Rubus idaeus L. (red raspberry) blocks UVB-induced MMP production and promotes type I procollagen synthesis via inhibition of MAPK/AP-1, NF-κβ and stimulation of TGF-β/Smad, Nrf2 in normal human dermal fibroblasts

Chronic exposure to ultraviolet (UV) radiation causes photo-oxidation, which in turn results in the upregulation of matrix metalloproteinases (MMPs) and loss of collagen. Rubus idaeus L. (RI), also called red raspberry, is an important cash crop that contains abundant antioxidant compounds. Sanguiin H-6 and lambertianin C are the major ingredients presented in the extracts. Here, we studied the protective effect of RI on UVB-induced photoaging in normal human dermal fibroblasts (NHDFs). We found that RI notably reduced UVB-induced MMPs secretion and pro-inflammatory mediators production, and significantly suppressed UVB-induced activation of mitogen-activated protein kinase (MAPK), nuclear factor-κβ, as well as activator protein 1. Additionally, treatment of NHDFs with the ERK inhibitor (PD98059) and JNK inhibitor (SP600125) resulted in the reduction of UVB-induced MMP-1 and IL-6 expressions, which demonstrated that the inhibition of MMP-1 and IL-6 by RI is associated with the MAPK pathway. Furthermore, we also found that RI accelerated procollagen type I synthesis by activating the transforming growth factor-β/Smad pathway and enhanced the expression of cytoprotective antioxidants such as heme oxygenase-1 and NHD(P)H quinone oxidoreductase 1 by promoting nuclear factor E2-related factor 2 nuclear transfer. Overall, these findings demonstrated that RI was potentially effective in preventing UVB induced skin photoaging.

MORIN PREVENTS ULTRAVIOLET-B RADIATION-INDUCED PHOTOCARCINOGENESIS THROUGH ACTIVATING THROMBOSPONDIN-1 IN THE MOUSE SKIN

Objective: In this study, we investigated whether morin, a natural flavonoid, could able to inhibit ultraviolet B (UVB)-induced carcinogenesis in the skin of Swiss albino mice.Methods: The mice were exposed to UVB radiation (180 mJ/cm2) on weekly thrice for 30 weeks, and morin was administered intraperitoneal and topical application 1 h before UVB exposure. UVB radiation induces the overexpression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and Bcl-2 genes.Results: Morin significantly prevented UVB-induced activation of COX-2, iNOS, VEGF, TGF-β, and Bcl-2 expression in mouse skin. Thrombospondin-1 (TSP), a novel endogenous factor, inhibits angiogenesis and inflammation.Conclusion: The present study illustrates that the protective effect of morin against UVB-induced carcinogenesis may be modulated through activation of TSP-1 in UVB-exposed Swiss albino mice.

The Mechanisms of Carnosol in Chemoprevention of Ultraviolet B-Light-Induced Non-Melanoma Skin Cancer Formation

Carnosol is a natural compound extracted from rosemary and sage, which has been demonstrated to have anti-inflammatory, anti-oxidant, and anti-cancer properties. In this report, we evaluated the therapeutic potential and elucidated the potential mechanism of action of carnosol in chemoprevention of ultraviolet B-light (UVB) induced non-melanoma skin cancer formation. Our data indicated that carnosol could partially reduce UVB-induced reactive oxygen species (ROS) elevation and thus reduce DNA damage. It could also reduce UVB-induced formation of cyclobutane pyrimidine dimers (CDP) in keratinocytes possibly through its ability in absorbing UVB radiation. In addition, carnosol could inhibit the UVB-induced activation of NF-κB and also reduce UVB-induced transformation of keratinocytes. Taken together, the results indicate the role of carnosol as a potential chemopreventive agent upon UVB radiation.

PAL-12, a new anti-aging hexa-peptoid, inhibits UVB-induced photoaging in human dermal fibroblasts and 3D reconstructed human full skin model, Keraskin-FT™.

Peptoids are a class of peptidomimetics whose pharmacological activities are widely investigated owing to their remarkable biological stability. However, the utilities of peptoids as cosmetic functional ingredients have not been fully explored. Here, we investigated anti-aging effects of PAL-12, a new hexa-peptoid, on UVB-induced photoaging in human dermal fibroblasts (HDFs) and a 3D reconstituted human full skin model, Keraskin-FT™. PAL-12 suppressed matrix metalloproteinase-1 (MMP-1) expression induced by UVB irradiation along with the attenuation of MMP-1 secretion as determined by ELISA assay. Interestingly PAL-12 slightly enhanced the expression levels of collagen-1 and fibronectin-1 in HDFs or Keraskin-FT™. In addition, PAL-12 prevented the decrease of cell viability following UVB irradiation. However, PAL-12 failed to affect ROS generation, cell necrosis and apoptosis significantly. Instead, PAL-12 suppressed UVB-induced activation of epidermal growth factor receptors (EGFR), extracellular signal-regulated kinase (ERK) and c-Jun, which may resulted in the attenuation of AP-1-promoted MMP-1 expression. Collectively, these results suggest that PAL-12 might be a novel cosmetic ingredient effective against UVB-induced skin photoaging.

Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells.

Ultraviolet-B radiation (285–320 nm) elicits a number of cellular signaling elements. We investigated the preventive effect of linalool, a natural monoterpene, against UVB-induced oxidative imbalance, activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling in HDFa cells. We observed that linalool treatment (30 μM) prevented acute UVB-irradiation (20 mJ/cm2) mediated loss of activities of antioxidant enzymes in HDFa cells. The comet assay results illustrate that linalool significantly prevents UVB-mediated 8-deoxy guanosine formation (oxidative DNA damage) rather than UVB-induced cyclobutane pyrimidine (CPD) formation. This might be due to its ability to prevent UVB-induced ROS formation and to restore the oxidative imbalance of cells. This has been reflected in UVB-induced overexpression of MAPK and NF-κB signaling. We observed that linalool inhibited UVB-induced phosphorylation of ERK1, JNK and p38 proteins of MAPK family. Linalool inhibited UVB-induced activation of NF-κB/p65 by activating IκBa. We further observed that UVB-induced expression of TNF-α, IL6, IL-10, MMP-2 and MMP-9 was modulated by linalool treatment in HDFa cells. Thus, linalool protects the human skin cells from the oxidative damages of UVB radiation and modulates MAPK and NF-κB signaling in HDFa cells. The present findings substantiate that linalool may act as a photoprotective agent against UVB-induced skin damages.

Extract from Periostracum cicadae Inhibits Oxidative Stress and Inflammation Induced by Ultraviolet B Irradiation on HaCaT Keratinocytes.

Periostracum cicadae is widely used for the treatment of skin diseases such as eczema, pruritus, and itching. The current study sought to evaluate the effect of P. cicadae extract on ultraviolet B (UVB) irradiation and identify the mechanisms involved. Photodamage-protective activity of P. cicadae extracts against oxidative challenge was screened using HaCaT keratinocytes. P. cicadae extracts did not affect cell viability but decreased reactive oxygen species (ROS) production. The extract attenuates the expression of interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and MMP-9 in UVB-treated HaCaT cells. Also, P. cicadae abrogated UVB-induced activation of NF-κB, p53, and activator protein-1 (AP-1). The downmodulation of IL-6 by P. cicadae was inhibited by the p38 inhibitor (SB203580) or JNK inhibitor (SP600125). Moreover, the extract attenuated the expression of NF-κB and induced thrombomodulin in keratinocytes and thereby effectively downregulated inflammatory responses in the skin. The nuclear accumulation and expression of NF-E2-related factor (Nrf2) were increased by P. cicadae treatment. Furthermore, treatment with P. cicadae remarkably ameliorated the skin's structural damage induced by irradiation. This study demonstrates that P. cicadae may protect skin cells against oxidative insult by modulating ROS concentration, IL-6, MMPs generation, antioxidant enzymes activity, and cell signaling pathways.

Inhibition of the MAPK Signaling Pathway by Red Rice Extract in UVB-irradiated Human Skin Fibroblasts

Red rice has demonstrated several biological properties including anti-oxidant and anti-inflammation properties. However, the anti-photoaging activity has not yet been investigated; The aim of this study relates to the photo-protective effects of red rice extract (RRE) on UVB-induced skin aging. RRE was prepared and the active compounds and anti-oxidant activity were determined. The cytotoxicity of fibroblasts and secretions of IL-6 and IL-8 were evaluated. The effects of RRE on collagen and hyaluronic acid (HA) synthesis from fibroblasts were evaluated. Then, the collagenase and MMP-2 activity was determined. The effect of RRE on UV-induced MMP-1, nuclear factor kappa B (NF-κB), activator protein-I (AP-1) and phosphorylation of MAPK protein expression was determined by western blot analysis. The RRE exerted a free radical scavenging property. RRE significantly increased collagen and HA synthesis in UVB-irradiated human fibroblasts. Moreover, RRE significantly inhibited UVB induced MMP- 1 expression, MMP-2 and collagenase activity. Upon UVB irradiation, mitogen activated protein kinases (MAPKs) is activated and this pathway stimulates the expression of interleukin-6 and-8 (IL-6 and-8). Our results show that RRE decreases UVB-induced IL-6 and -8 production and the phosphorylation of c-Jun NH2- terminal kinase (JNK) and the p38 MAPK signaling process. In addition, RRE reduced UVB-induced activation of NF-icB and AP-I. RRE could suppress UV-induced inflammation and skin aging via the inhibition of the MAPK signaling pathway leading to the decrease of NF-cB and AP- 1 activation resulting in a decrease in ECM degradation and an increase in ECM synthesis.

TNF-R1 and FADD mediate UVB-Induced activation of K+ channels in corneal epithelial cells

The goal of this study was to elucidate the role of Fas, TNF-R1, FADD and cytochrome c in UVB-induced K+ channel activation, an early step in UVB-induced apoptosis, in human corneal limbal epithelial (HCLE) cells. HCLE cells were treated with Fas, TNF-R1 or FADD siRNA and exposed to 80 or 150 mJ/cm2 UVB. K+ channel activation and loss of intracellular K+ were measured using whole-cell patch-clamp recording and ion chromatography, respectively. Cytochrome c was measured with an ELISA kit. Cells in which Fas was knocked down exhibited identical UVB-induced K+ channel activation and loss of intracellular K+ to control cells. Cells in which TNF-R1 or FADD were knocked down demonstrated reduced K+ channel activation and decreased loss of intracellular K+ following UVB, relative to control cells. Application of TNF-α, the natural ligand of TNF-R1, to HCLE cells induced K+ channel activation and loss of intracellular K+. Cytochrome c was translocated to the cytosol by 2 h after exposure to 150 mJ/cm2 UVB. However, there was no release by 10 min post-UVB. The data suggest that UVB activates TNF-R1, which in turn may activate K+ channels via FADD. This conclusion is supported by the observation that TNF-α also causes loss of intracellular K+. This signaling pathway appears to be integral to UVB-induced K+ efflux, since knockdown of TNF-R1 or FADD inhibits the UVB-induced K+ efflux. The lack of rapid cytochrome c translocation indicates cytochrome c does not play a role in UVB-induced K+ channel activation.