UVB-induced MMP-1 Expression Research Articles

Suppression of UVB-Induced MMP-1 Expression in Human Skin Fibroblasts Using Lysate of Lactobacillus iners Derived from Korean Women's Skin in Their Twenties.

The process of skin aging is intricate, involving intrinsic aging, influenced by internal factors, and extrinsic aging, mainly caused by exposure to UV radiation, resulting in photoaging. Photoaging manifests as skin issues such as wrinkles and discoloration. The skin microbiome, a diverse community of microorganisms on the skin's surface, plays a crucial role in skin protection and can be affected by factors like humidity and pH. Probiotics, beneficial microorganisms, have been investigated for their potential to enhance skin health by regulating the skin microbiome. This can be accomplished through oral probiotics, impacting the gut-skin axis, or topical applications introducing live bacteria to the skin. Probiotics mitigate oxidative stress, suppress inflammation, and maintain the skin's extracellular matrix, ultimately averting skin aging. However, research on probiotics derived from human skin is limited, and there is no established product for preventing photoaging. The mechanism by which probiotics shield the skin microbiome and skin layers from UV radiation remains unclear. Recently, researchers have discovered Lactobacillus in the skin, with reports indicating a decrease in this microorganism with age. In a recent study, scientists isolated Lactobacillus iners KOLBM20 from the skin of individuals in their twenties and confirmed its effectiveness. A comparative analysis of genetic sequences revealed that strain KOLBM20 belongs to the Lactobacillus genus and closely relates to L. iners DSM13335(T) with a 99.20% similarity. Importantly, Lactobacillus iners KOLBM20 displayed anti-wrinkle properties by inhibiting MMP-1. This investigation demonstrated the inhibitory effect of KOLBM20 strain lysate on MMP-1 expression. Moreover, the data suggest that KOLBM20 strain lysate may prevent UVB-induced MMP-1 expression by inhibiting the activation of the ERK, JNK, and p38 signaling pathways induced by UVB. Consequently, KOLBM20 strain lysate holds promise as a potential therapeutic agent for preventing and treating skin photoaging.

Oral intake of collagen hydrolysate from mackerel scad (Decapterus macarellus) attenuates skin photoaging by suppressing the UVB-induced expression of MMP-1 and IL-6.

Excessive skin exposure to UVB radiation can induce photoaging caused by an imbalance in oxidative stress and inflammatory responses, damaging the skin's structure and surface layer. A previous study revealed that collagen hydrolisate extracted from the skin of mackarel scads (Decapterus macarellus) had antiaging properties thatwere tested invitro, which serves as a foundation for asubsequent study of its use invivo. This study aimed at investigating the repair effect of the mackerel scad's skin collagen hydrolysate (MSS-CH) in photoaging conditions in amouse model. MSS-CH was given orally in mice model of skin photoaging under chronic exposure to UVB irradiation for12weeks. Morphological and histological changes on the skin were evaluated using SEM and HE staining, along withthe measurement of the expression of matrix metalloproteinases (MMP-1) and cytokine pro-inflammatory interleukin 6 (IL-6) using ELISA. MSS-CH inhibits the occurrence of epidermal thickening and damage to the dermal layer of the skin. As aresult, it restores the epidermis' barrier function and reduces surface damage caused by photoaging. The skin ofthe MSS-CH treated group exhibited improved physical appearance with reduced fine lines, wrinkles, and enhanced smoothness. Additionally, administering MSS-CH to the mice groups reduced the expression of MMP-1 and IL-6 in UVB-exposed skin. Altogether, this invivo study demonstrates thephotoaging-protective properties of CH-MSS, aligning with previous invitro data. Thus, MSS-CH emerges as a strong candidate for use as an ingredient in nutraceuticals and biocosmetics.

Amentoflavone-Enriched Selaginella rossii Protects against Ultraviolet- and Oxidative Stress-Induced Aging in Skin Cells.

Selaginellaceae plants are used in cosmetics to limit skin aging. This study is the first to investigate the anti-aging effects of Selaginella rossii (SR) on ultraviolet B (UVB)- and oxidative stress-induced skin cells. The 95% ethanol extract of Selaginella rossii (SR95E) contained much higher amounts of amentoflavone (AMF), an active compound, than other Selaginellaceae plants and was more effective in inhibiting matrix metalloproteinase (MMP)-1 expression in CCD-986sk fibroblasts. SR95E significantly decreased UVB-induced MMP-1, MMP-2, MMP-3 and MMP-9 expression and enhanced procollagen type I C-peptide content and mRNA expression of collagen type I alpha (COL1A)1 and COL1A2 in CCD-986sk fibroblasts. In HaCaT keratinocytes, SR95E treatment also dose-dependently decreased UVB-induced MMP-1 concentration and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA expression. Moreover, SR95E treatment markedly inhibited UVB-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling and nuclear factor kappa-B signaling in HaCaT cells. Furthermore, SR95E and AMF markedly regulated the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced expression of cellular senescence-related markers, including p16, p21 and LMNB1, in HaCaT cells. Overall, this study indicates that SR may have potential as a functional material on preventing UVB- and AAPH-induced skin aging and wrinkles.

Protective effects of Evodiae Fructus extract against ultraviolet-induced MMP-1 and MMP-3 expression in human dermal fibroblasts

Evodiae Fructus (EF) has been used as a traditional medicine for abdominal pain, headache, bleeding, and menorrhea in Asian countries. However, the effect of EF extract (EFE) on ultraviolet (UV)B-induced photoaging remains unknown. This study aimed to investigate the effects and molecular mechanisms of UVB-induced matrix metalloproteinase (MMP)−1 and MMP-3 expression in primary human dermal fibroblasts (HDFs). In HDFs, the expression of MMP-1, MMP-3 and pro-collagenA2 were analyzed using western blotting and real-time polymerase chain reaction. The phosphorylation levels of mitogen-activated protein kinase (MAPK) and activation of nuclear factor (NF)-κB and activator protein (AP)−1 were assessed using western blotting. Results showed that EFE reduced UVB-induced MMP-1 and MMP-3 expression, and this effect was mediated by the inhibition of MAPK/NF-κB and AP-1 activation. Moreover, EFE prevented UVB-induced inhibition of collagen synthesis. Taken together, these results suggest that EFE may have a preventive potential against photoaging.

Transglutaminase 2 mediates UVB-induced matrix metalloproteinase-1 expression by inhibiting nuclear p65 degradation in dermal fibroblasts.

Matrix metalloproteinases (MMPs) play a key role in tissue remodelling by cleaving extracellular matrix (ECM) components. In the skin, UV irradiation increases expression of MMPs that causes dysregulation of ECM homeostasis in dermis, leading to acceleration of skin aging. However, the mediator(s) that links UV irradiation to the upregulation of MMPs have not been fully defined. Previously, we showed that UVB irradiation activated transglutaminase 2 (TG2) in keratinocytes, eliciting an inflammatory response by activating NF-κB signalling. In this study, we reported the role of TG2 in mediating the UVB-induced expression of MMP-1. In human dermal fibroblasts, UVB irradiation enhanced the expression and activity of TG2, which in turn promotes the expression of MMP-1. Analyses of MMP-1 promoter showed that activation of the NF-κB signalling pathway, rather than AP-1, was responsible for the TG2-mediated upregulation of MMP-1. Moreover, Western blot analysis revealed that TG2 increased the activity of NF-κB by inhibiting degradation of p65 in the nucleus. Furthermore, ex vivo skin from TG2-knockout mice exhibited significantly reduced levels of MMP-1 compared to that from wild-type mice. These results indicate that TG2 functions as a mediator for the UVB-induced expression of MMP-1 in dermal fibroblasts, providing a new target for preventing skin photodamage.

Acetylated Resveratrol and Oxyresveratrol Suppress UVB-Induced MMP-1 Expression in Human Dermal Fibroblasts.

Resveratrol (RES) and oxyresveratrol (OXYRES) are considered and utilized as active ingredients of anti-aging skin cosmetics. However, these compounds are susceptible to oxidative discoloration and unpleasant odor in solutions, limiting their use in cosmetics. Accordingly, RES and OXYRES were chemically modified to acetylated derivatives with enhanced stability, and their anti-aging effect on the skin and detailed molecular mechanism of their acetylated derivatives were investigated. Acetylated RES and OXYRES lost their acetyl group and exerted an inhibitory effect on H2O2-induced ROS levels in human dermal fibroblast (HDF) cells. In addition, RES, OXYRES, and their acetylated derivatives suppressed UVB-induced matrix metalloproteinase (MMP)-1 expression via inhibition of mitogen-activated protein kinases (MAPKs) and Akt/mTOR signaling pathways. Furthermore, RES, OXYRES, and their acetylated derivatives suppressed type I collagen in TPA-treated HDF cells. Collectively, these results suggest the beneficial effects and underlying molecular mechanisms of RES, OXYRES, and their acetylated derivatives for anti- skin aging applications.

PARP-1 involves in UVB-induced inflammatory response in keratinocytes and skin injury via regulation of ROS-dependent EGFR transactivation and p38 signaling.

UV irradiation can injure the epidermis, resulting in sunburn, inflammation, and cutaneous tissue disorders. Previous studies demonstrate that EGFR in keratinocytes can be activated by UVB and contributes to inflammation. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and plays an essential role in DNA repair under moderate stress. In this study, we set out to understand how PARP-1 regulates UVB irradiation-induced skin injury and interplays with EGFR to mediate the inflammation response. We found that PARP-1 deficiency exacerbated the UVB-induced inflammation, water loss, and back skin damage in mice. In human primary keratinocytes, UVB can activate PARP-1 and enhance DNA damage upon PARP-1 gene silencing. Moreover, PARP-1 silencing and PARP inhibitor olaparib can suppress UVB-induced COX-2 and MMP-1 expression, but enhance TNF-α and IL-8 expression. In addition, EGFR silencing or EGFR inhibition by gefitinib can decrease UVB-induced COX-2, TNF-α, and IL-8 expression, suggesting EGFR activation via paracrine action can mediate UVB-induced inflammation responses. Immunoblotting data revealed that PARP-1 inhibition decreases UVB-induced EGFR and p38 activation. Pharmacological inhibition of p38 also dramatically led to the attenuation of UVB-induced inflammatory gene expression. Of note, genetic ablation of PARP-1 or EGFR can attenuate UVB-induced ROS production, and antioxidant NAC can attenuate UVB-induced EGFR-p38 signaling axis and PARP-1 activation. These data suggest the regulatory loops among EGFR, PARP-1, and ROS upon UVB stress. PARP-1 not only serves DNA repair function but also orchestrates interactions to EGFR transactivation and ROS production, leading to p38 signaling for inflammatory gene expression in keratinocytes.

645 5-(3’, 4’-Dihydroxyphenyl-valerolactone) regulates DNA methylation in UVB-irradiated keratinocytes

5-(3’,4’-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a colonic microbial metabolite derived from cacao. In the previous study, we found that cacao powder modulates DNA methylation and inhibits UVB-induced AP-1 activation and MMP-1 expression. To further investigate whether major metabolite of cacao, DHPV, has UV protective effect as cacao, we evaluated the regulatory role of DHPV on DNA methylation in keratinocytes after UVB irradiation. In this study, we found that UVB irradiation altered methylation profiles in HaCaT cells and these changes were ameliorated by DHPV.

Ginsenoside C-Mx Isolated from Notoginseng Stem-leaf Ginsenosides Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create a reaction with the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1 and IL-6 expression while accelerating TGF-β and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-β/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, application of ginsenoside C-Mx treatment (1, 10, 20μm) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage.

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam (Limnanthes alba) Against UVB Irradiation in Human Skin Equivalent.

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam (Limnanthes alba) glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure. To that end, we have exposed human primary epidermal keratinocytes (HPEKs) and 3D human skin reconstructed in vitro (EpiDermTM FT-400) to UVB insult and investigated whether MBITC and MPACN treatment ameliorated the harmful effects of UVB damage. Activity was determined by the compounds’ efficacy in counteracting UVB-induced DNA damage, matrix-metalloproteinase (MMP) expression, and proliferation. We found that in monolayer cultures of HPEK, MBITC and MPACN did not protect against a UVB-induced loss in proliferation and MBITC itself inhibited cell proliferation. However, in human reconstructed skin-equivalents, MBITC and MPACN decrease epidermal cyclobutane pyrimidine dimers (CPDs) and significantly reduce total phosphorylated γH2A.X levels. Both MBITC and MPACN inhibit UVB-induced MMP-1 and MMP-3 expression indicating their role to prevent photoaging. Both compounds, and MPACN in particular, showed activity against UVB-induced proliferation as indicated by fewer epidermal PCNA+ cells and prevented UVB-induced hyperplasia as determined by a reduction in reconstructed skin epidermal thickness (ET). These data demonstrate that MBITC and MPACN exhibit promising anti-photocarcinogenic and anti-photoaging properties in the skin microenvironment and could be used for therapeutic interventions.

Preventive effect of Ephedra sinica extract on UVB-induced COX-2 and MMP-1 expression.

Ultraviolet B (UVB)-induced cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-1 are representative markers for skin inflammation and photoaging, respectively. To evaluate compounds that may counteract the effects of UVB-induced skin damage, we developed an immortalized human keratinocyte (HaCaT) cell line with an MMP-1 reporter construct. Among the 30 botanical extracts screened, we selected Ephedra sinica extract (ESE) as a promising candidate and confirmed that ESE significantly suppresses UVB-induced COX-2 and MMP-1 expression in HaCaT cells. Treatment with ESE also potently suppressed UVB-induced ERK1/2 phosphorylation, as well as UVB-induced MEK1/2 and Raf phosphorylation in HaCaT cells. These findings suggest that our MMP-1 reporter system can be used to evaluate compounds with anti-inflammatory and anti-photoaging effects. We also report that ESE has potent suppressive effects against COX-2 and MMP-1 expression, which occurs via downregulation of Raf/MEK1/2/ERK1/2 phosphorylation.

Suppression of Ultraviolet B-mediated Matrix Metalloproteinase Generation by Sorbus commixta Twig Extract in Human Dermal Fibroblasts.

Sorbus commixta is a traditional oriental medicinal plant that grows in East Asian countries such as Korea, Japan and China. The twig of S.commixta has been considered valuable for centuries to treat diseases including asthma, cough and other bronchial disorders. However, the effect of S.commixta twig extract on human skin has not been investigated well. The present study aimed at assessing the antiphotoaging effect of S.commixta twig ethanol extract (STE) on ultraviolet B (UVB)-induced matrix metalloproteinase (MMP) levels and its underlying mechanism in human dermal fibroblasts. In this study, we found that STE (12.5-50μgmL-1 ) treatment significantly inhibited UVB-induced MMP-1, MMP-2 and MMP-3 expression, concomitant with a downregulation of intracellular ROS generation. These effects might be associated with a STE-induced inhibition of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, STE also downregulated UVB-induced c-Fos expression in a concentration-dependent manner, but had no inhibitory effect on c-Jun phosphorylation. Taken together, these results indicate that STE may be an antiphotoaging agent and that its effect may occur via its inhibition of MMPs expression and MAPK pathway activation.

Guaiane Sesquiterpenes from the Rhizome of Curcuma xanthorrhiza and Their Inhibitory Effects on UVB-induced MMP-1 Expression in Human Keratinocytes

A new guaiane sesquiterpene, (1 R,4 S,5 S,10 R)-10-methyl guaianediol (1), along with five known compounds, 10-methylalismoxide (2), (+)-alismoxide (3), isozedoarondiol (4), zedoarondiol (5), and zedoalactone B (6), were isolated from the rhizomes of Curcuma xanthorrhiza Roxb. Compounds 1-6 were isolated from this plant for the first time. Chemical structures were determined using nuclear magnetic resonance (NMR), electron ionization mass spectrometry (EI/MS), polarimetry, circular dichroism (CD), and infrared spectroscopy (IR). Compounds 3 and 4 decreased MMP-1 expression in UVB-treated human keratinocytes by about 8.9-fold and 7.6-fold at the mRNA level, and by about 9.2-fold and 6.6-fold at the protein level, respectively. Results indicate that the isolated compounds have anti-aging effects by inhibiting MMP-1 expression in skin cells.

Protective effect of polysaccharides from Sargassum fusiforme against UVB-induced oxidative stress in HaCaT human keratinocytes

In this study, Sargassum fusiforme polysaccharide was purified using a DEAE-Sepharose fast-flow column to obtain Sargassum fusiforme polysaccharides fraction (SFP-P1). As expected, the SFP-P1 contains mainly carbohydrates (87%) with less than 1% protein. Within the carbohydrate, it contains about 10% sulfate and 18% uronic acids. SFP-P1 consisted of l-fucose (13.17%), galactose (4.28%), glucose (1.95%), xylose (5.50%), and mannose (75.10%) with an average molecular weight of 113kDa. Mannose and l-fucose were two predominant monosaccharides. In addition, (1→)-linked or (1→6)-linked, (1→2)-linked or (1→4)-linked and (1→3)-linked glycosyl linkages accounted for 1.62%, 60.69% and 37.69% of all linkages in the molecule, respectively. The glycosidic linkage types of SFP-P1 were proven to be→3,6)-α-d-Manp(1→,→4)-α-d-GalAp(1→,→4)-β-d-Xylp(1→and→3,4)-α-d-GlcAp(1→. The results indicated the SFP-P1 had cytoprotective activity against UVB-induced oxidative stress in HaCaT cells through stimulation of SOD, GSH-PX enzymes activities and ROS. Also SFP-P1 suppressed the UVB-induced expression of MMP-1 & MMP-9.

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.

Preventive effect of Rhus javanica extract on UVB-induced skin inflammation and photoaging

Rhus javanica has long been used in traditional medicines, and found to possess bioactive properties. In this study, we sought to investigate whether Rhus javanica extract (RJE) has preventive effects against UVB-induced inflammation and photoaging. RJE was identified as a promising candidate based on an MMP-1 promoter assay, and we confirmed suppressive effects on UVB-induced COX-2 and MMP-1 expression (67.6% and 80.9%, respectively) in immortalized human keratinocyte HaCaT cells. RJE suppressed both UVB-induced mitogen activated protein kinase (MAPK) and Akt signalling pathways as well as EGFR activity. RJE significantly suppressed repetitive UVB-induced wrinkle formation and COX-2 and MMP-13 expression in vivo. Among the compounds identified, syringic acid was found to exhibit the strongest inhibitory effect on UVB-induced MMP-1 promoter activity (45.2%). These results demonstrate that RJE has potent preventive activity for skin inflammation and photoaging which occurs via suppression of pathways related to EGFR.

A polymethoxyflavone mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1.

Ultraviolet (UV) B is the main cause of skin photoageing, which has characteristic features such as deep wrinkles. UVB increases the expression of matrix metalloproteinases (MMPs) in the skin and can cause wrinkles by disrupting components of the extracellular matrix, such as collagen fibres. We now report that a polymethoxyflavone (PMF) mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1 that involves the inhibition of c-jun N-terminal kinase (JNK) activity. Furthermore, the PMF mixture also inhibits the UVB-induced phosphorylation of JNK. Therefore, the results suggest that the PMF mixture suppresses the UVB-induced expression of MMP-1 through the inhibition of JNK phosphorylation and should be useful as an antiphotoageing agent.

Ethanol extract of Terminalia chebula fruit protects against UVB-induced skin damage

Context: The fruit of Terminalia chebula Retz. (Combretaceae) has been used for several therapeutic purposes in Thai folk medicines. Currently, the ethanol extracts containing antioxidant compounds have shown the ability to promote collagen synthesis.Objective: This purpose of this work was to study the effects of the ethanol extract from T. chebula fruit on the inhibition of cutaneous photodamage.Materials and methods: The viability of human skin fibroblasts after incubation with T. chebula at concentration 0.5–50 μg/mL for 24, 48 and 72 h was assessed by using sodium 3′-[(phenyl-amino)-carbonyl]-3,4,tetrazolium-bis(4-methoxy-6-notro)benzene-sulphonic acid hydrate (XTT). The levels of type I procollagen and matrix metalloproteinases (MMP)-1 and MMP-13 produced by UVB-irradiated fibroblasts were determined by ELISA. Skin thickness and collagen content caused by long-term UVB irradiation in male ICR mice were determined from haematoxylin and eosin stained tissue sections and spectrophotometric measurement of hydroxyproline.Results: The extract (0.5–50 μg/mL) had no effect on cell viability or morphology of the human fibroblasts. In vitro studies showed that the T. chebula extract reduced the UVB-induced MMP-1 and MMP-13 expression, whereas an increased production of type I procollagen was observed. In a UVB-irradiated animal model, male ICR mice with hair shaved were chronically exposed to UVB which lead to epidermal thickness and loss of hydroxyproline. However, these effects were fully prevented by the topical application of the T. chebula ethanol extract.Discussion and conclusion: These data suggested that the T. chebula ethanol fruit extract is an efficacious pharmaceutical protectant of skin against photodamage.

Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging

While skin aging is a naturally occurring process by senescence, exposure to ultraviolet (UV) radiation accelerates wrinkle formation and sagging of skin. UV induces skin aging by degrading collagen via activating matrix metalloproteinases (MMPs). In this study, we show that coumestrol, a metabolite of the soybean isoflavone daidzein, has a preventive effect on skin photoaging in three-dimensional human skin equivalent model. Coumestrol inhibited UVB-induced MMP-1 expression and activity. Whole human kinase profiling assay identified FLT3 kinase as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70 ribosomal S6 kinase pathway. This suppresses AP-1 activity and in turn, diminishes MMP-1 gene transcription. Using X-ray crystallography, the binding of coumestrol to FLT3 was defined and implied ATP-competitive inhibition. Residues Lys644 and Phe830 showed local changes to accommodate coumestrol in the ATP-binding pocket. 4-APIA, a pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced signal transduction changes similar to coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. These findings suggest that coumestrol is a novel dietary compound with potential application in preventing and improving UVB-associated skin aging.

Abietic acid inhibits UVB-induced MMP-1 expression in human dermal fibroblast cells through PPARα/γ dual activation.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and consist of three isotypes: PPARα, PPARβ/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato-endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin. Intensive studies have revealed that PPARα/γ functions in photoageing and age-related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB-induced MMP-1 expression by downregulating UVB-induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB-induced MMP-1 expression and inflammatory signalling pathway activation. Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB-induced MMP-1 expression and age-related inflammation by suppressing NF-κB and the MAPK/AP-1 pathway and can be a useful agent for improving skin photoageing.