Effects of phenylethanol glycosides from Orobanche cernua Loefling on UVB-Induced skin photodamage: a comparative study.

Previous study has found that Orobanche cernua Loefling(OC) and its main ingredient, acteoside, possess excellently anti-photo-aging effect. In addition to acteoside, crenatoside, isoacteoside and 2'-acetylacteoside were also identified as the main phenylethanol glycosides (PhGs) in OC. To screen optimum effective substance and further clarify the photoprotective ingredients of OC, the effects of four major PhGs in OC were compared using UVB-irradiated HaCaT cells. Results indicated that acteoside, isoacteoside and 2'-acetylacteoside effectively decreased UVB-induced MMP-1 expression and stimulated type I procollagen synthesis through inhibition of MAPK/AP-1 and activation of TGF-ß/Smad pathway. Moreover, acteoside and 2'-acetylacteoside significantly reduced UVB-induced ROS and TARC secretion, which is involved in the inhibition of NF-κß/Iκßα and stimulation of Nrf2 antioxidant defense system. However, crenatoside did not show any effect on the regulation of signal cascades mentioned above. Together, our results suggested that 2'-acetylacteoside and isoacteoside also served as efficient agents against UV radiation-induced skin damage. Among them, acteoside and 2'-acetylacteoside showed a higher efficiency than that of isoacteoside, which possessed great potential in treating skin photo-damage.

Crataegus laevigata Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways.

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment.

Mixture of enzyme-processed Panax ginseng and Gastrodia elata extract prevents UVB-induced decrease of procollagen type 1 and increase of MMP-1 and IL-6 in human dermal fibroblasts.

According to the previously described anti-photoaging effect of the enzyme-processed Panax ginseng extract and Gastrodia elata extract, we hypothesized that the combination of the two extracts would have superior effect to protect human skin from UVB radiation. Besides, the mixture of active components isolated from herbal extracts, ginsenoside F2, and α-gastrodin was investigated on the photo-protective capability. The expression of aging-related markers including matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and procollagen type 1 was evaluated using ELISA kits. It was reported that the herbal extract at a Panax ginseng extract to Gastrodia elata extract ratio of 1:10 (w/w) and the compound mixture with equal proportion of ginsenoside F2 and α-gastrodin exhibited significant inhibition of MMP-1 and IL-6 production, and marked upregulation of procollagen type 1 formation. Thus, the combination of either the enzyme-processed herbal extracts or their active components would enhance the properties of prevention and treatment of UVB-induced skin damage.

Helianthus annuus L. flower prevents UVB-induced photodamage in human dermal fibroblasts by regulating the MAPK/AP-1, NFAT, and Nrf2 signaling pathways.

BACKGROUND: Excessive ultraviolet radiation usually causes skin photoaging, inflammation, and even photocarcinogenesis. UV radiation-generated reactive oxygen species (ROS) are a major contributing factor to photodamage. The flowers of Helianthus annuus L. have been reported to possess strong anti-inflammatory and antioxidant activity. However, there are few reports on the use of H. annuus L. to relieve UVB-induced photoaging. PURPOSE: In this study, we evaluated the protective effect of a 50% ethanol extract of H. annuus L. flower (HAF) against UVB-induced photodamage using normal human dermal fibroblasts. METHODS: The secretion of ROS, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), procollagen type I, and transforming growth factor-ß1 (TGF-ß1) was measured with kits. The messenger RNA levels of COX-2, iNOS, and TGF-α were measured by RT-PCR. The AP-1, MAPK, NFAT, and Nrf2 pathways were investigated by Western blot analysis. RESULTS: HAF extract significantly blocked UVB-induced ROS and MMP (MMP-1 and MMP-3) production and procollagen type I reduction. Further study demonstrated that the photoaging inhibitory actions were related to promotion of Nrf2 nuclear translocation, upregulation of TGF-ß1 level, and downregulation of AP-1 and MAPK phosphorylation. Importantly, HAF effectively inhibited UVB-induced VEGF and inflammatory cytokines such as IL-6, COX-2, iNOS, and TNF-α secretion, which might be involved in the regulation of the NFAT signaling pathway. CONCLUSION: Our results indicate that HAF is a useful botanical source protecting against UVB-mediated skin photodamage.

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.

Correction: Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes.

Correction for 'Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes' by Eunson Hwang et al., Photochem. Photobiol. Sci., 2018, 17, 1396-1408.

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

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

Eucalyptus globulus extract protects against UVB-induced photoaging by enhancing collagen synthesis via regulation of TGF-ß/Smad signals and attenuation of AP-1.

UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 µg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-ß1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-ß/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-ß1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products.

Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and reducing AP-1 and NF-κB signaling pathways: a comparative study on UVB-irradiated human keratinocytes.

Icariin (ICA) and icaritin (ICT) exhibit many pharmacological functions including anti-osteoporosis, anti-cardiovascular, and anti-cancer activities; however, there are few comprehensive studies that track the detailed effects on UVB-induced photoaging. The recovery effects of ICA and ICT were investigated in UVB-irradiated human keratinocytes (HaCaTs). The results indicated that ICT and ICA showed strong radical scavenging activity, and the reactive oxygen species (ROS) scavenging activity of ICT was superior. UVB-induced matrix metalloproteinase-1 (MMP-1) expression was blocked by ICA via the inhibition of mitogen-activated protein kinase/activator protein 1 (MAPK/AP-1), which directly reduced extracellular matrix (ECM) degradation. ICT activated nuclear factor erythroid 2 related factor 2 (Nrf2) to improve the anti-oxidative stress capacity and suppress nuclear factor-κB (NF-κB) activation, decreasing vascular endothelial growth factor (VEGF) protein, and inflammatory cytokines induced ECM degrading enzyme secretion. Moreover, ICT was more advantageous to improve transforming growth factor beta 1 (TGF-ß1) and procollagen type I expression than ICA, promoting the synthesis of collagen. Therefore, ICA and ICT have potential to treat UVB-induced oxidative stress, inflammation and photoaging, and will be posited as a novel strategy to alleviate photodamage.

Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB-induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP-1 pathway.

Paeonia suffruticosa Andr. (PS) has been used in traditional Chinese medicine for a long time. However, there are no studies that investigate the preventive effects of PS on ultraviolet B (UVB)-induced photoaging. In this study, paeonol (PA) was detected the main compound in PS root. In vitro, PS and PA significantly inhibited UVB-induced phosphorylation of mitogen-activated protein kinase and activator protein 1 in keratinocytes, which consequently led to degradation of procollagen type I. On the other hand, PS and PA increased NAD(P)H:quinone oxidoreductase 1 and heme oxygenase-1 expression, confirmed by greater nuclear accumulation of nuclear factor E2-releated factor 2 (Nrf2). Furthermore, this study proved that the endogenous antioxidant system Nrf2/antioxidant response element was regulated by dihydrolipoamide dehydrogenase, a tricarboxylic acid (TCA) cycle-associated protein whose level was decreased after UVB exposure. PS and PA promoted the production of dihydrolipoamide dehydrogenase, as well as the activation of Nrf2 and antioxidant response element, resulting in preventing procollagen type I ruined caused by UVB. In vivo, topical application of PS and PA attenuated UVB-induced matrix metalloproteinase-1 production and promoted procollagen type I in hairless mice. These results suggested PA a promising botanical in protecting skin from UVB-induced photoaging.

Protective Effects of Euphrasia officinalis Extract against Ultraviolet B-Induced Photoaging in Normal Human Dermal Fibroblasts.

Ultraviolet (UV) radiation induces skin photoaging, which is associated with the elevation of matrix metalloproteinases (MMPs) and the impairment of collagen. The Euphrasia species play a well-known role in the treatment of certain eye disorders through their anti-oxidative and anti-inflammatory activities. However, their protective activity toward UVB-induced damage remains unclear. In the present study, we investigated the protective effect of Euphrasia officinalis (95% ethanol extract) on UVB-irradiated photoaging in normal human dermal fibroblasts (NHDFs). Our results show that Euphrasia officinalis extract exhibited obvious reactive oxygen species (ROS) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, enhanced NHDF cell migration, and reduced UVB-induced apoptosis. The UVB-induced increases in MMP-1 and MMP-3 and decrease in type I procollagen were ameliorated by Euphrasia officinalis treatment, which worked by suppressing the mitogen-activated protein kinase (MAPK) and nuclear transcription factor activator protein 1 (AP-1) signaling pathways. Taken together, our data strongly suggest that Euphrasia officinalis ethanol extract could reduce UVB-induced photoaging by alleviating oxidative stress, proinflammatory activity, and cell apoptosis.

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.

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 © 2016 John Wiley & Sons, Ltd.

The Androgenic Alopecia Protective Effects of Forsythiaside-A and the Molecular Regulation in a Mouse Model.

This study examined the inhibitory effect of forsythiaside-A, a natural substance derived from Forsythia suspensa (F. suspensa), on entry into catagen induced by dihydrotestosterone (DHT) in an androgenic alopecia mouse model. In vitro experiment comparing finasteride with forsythiaside-A showed that forsythiaside-A treatment resulted in a 30% greater inhibition of DHT-induced apoptosis in human hair dermal papilla cell (HHDPCs) and human keratinocytes (HaCaTs). In vivo experiment showed that mouse hair density and thickness were increased by 50% and 30%, respectively, in the forsythiaside-A-treated group when compared to a DHT group. Tissue histological results revealed that the forsythiaside-A-treated group had an increase in size and shape of the hair follicles and a 1.5 times increase in the follicle anagen/telogen ratio when compared to the finasteride group. Western blot examination of TGF-ß2 expression related to apoptosis signaling in mouse skin verified that forsythiaside-A reduced the expression of TGF-ß2 by 75% and suppressed apoptosis by reducing the expression of caspase-9 by 40%, and caspase-3 by 53%, which play an roles up-regulator in the apoptosis signal. The forsythiaside-A group also showed a 60% increase in the Bcl-2/Bax ratio, which is a factor related to mitochondrial apoptosis. Our results indicated that forsythiaside-A prevents apoptosis by similar mechanism with finasteride, but forsythiaside-A is more effective than finasteride. In summary, forsythiaside-A controlled the apoptosis of hair cells and retarded the entry into the catagen phase and therefore represents a natural product with much potential for use as a treatment for androgenic alopecia.

Nocatriones A and B, photoprotective tetracenediones from a marine-derived Nocardiopsis sp.

Two new tetracenedione derivatives, nocatriones A (1) and B (2), were discovered from the culture broth of a marine actinomycete, Nocardiopsis sp. KMF-002, which was isolated from the tissue of an unidentified dark purple marine sponge. The structures of 1 and 2, which are tetracenediones containing α-pyrone substituents, were determined to be 3,8,10,11-tetrahydroxy-2-(4-hydroxy-2-oxo-2H-pyran-6-yl)-1-methyltetracene-5,12-dione (1) and 3,8,10,12-tetrahydroxy-2-(4-hydroxy-2-oxo-2H-pyran-6-yl)-1-methyltetracene-6,11-dione (2). Ultraviolet B (UVB)-irradiated cells treated with 10 µM nocatrione A (1) significantly decreased the level of MMP-1, a protein that degrades collagen and other extracelluar matrix components that comprise dermal tissue, when compared to untreated cells. These results support that nocatriones A (1) and B (2) may show antiphotoaging activity in UVB-irradiated models.

Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-ß pathways in a dihydrotestosterone-induced mouse model.

This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-ß) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-ß2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-ß2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

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-ß1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging.

A comparative study of baby immature and adult shoots of Aloe vera on UVB-induced skin photoaging in vitro.

Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-ß1 (TGF-ß1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-ß1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-ß1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE.

The Protective Effect of Edible Bird's Nest against the Immune-senescence Process of UVB-irradiated Hairless Mice.

Edible bird's nest (EBN) is a nutritious food with many beneficial effects, including protecting cells against oxidation and infection due to wounds, bacteria or viruses. EBN has shown antiaging, anti-inflammatory and wound-healing properties in skin cells. Here, we investigated whether EBN has protective effects against photoaging, inflammation and immune-senescence in hairless mice treated with UVB irradiation. The skin thickness was lower in mice on an EBN diet than in mice treated with UVB alone. The level of hydration was significantly increased, while the index of transepidermal water loss decreased, in groups on the EBN diet. EBN also reduced erythema index in UVB-irradiated mice. At the molecular level, skin elasticity and antiaging are associated with high expression of elastin, collagen and filaggrin and low expression of the membrane metalloproteinases, MMP-1 and MMP-2. Inflammatory markers such as interleukins, IL-1ß and IL-6, and TNF-α decreased significantly in the EBN groups. Caspase-3, an important factor in the apoptotic pathway and in congenital and adaptive immune responses, decreased in the EBN groups. Moreover, EBN diminished the overexpression of immunoglobulin E and elevated mast cell counts in UVB-irradiated mice. Overall, these findings suggest that EBN protects skin against aging and alleviates inflammation in UVB-irradiated hairless mice.

Chemical Distance Measurement and System Pharmacology Approach Uncover the Novel Protective Effects of Biotransformed Ginsenoside C-Mc against UVB-Irradiated Photoaging.

Long-term exposure to ultraviolet light induces photoaging and may eventually increase the risk of skin carcinogenesis. Rare minor ginsenosides isolating from traditional medicine Panax (ginseng) have shown biomedical efficacy as antioxidation and antiphotodamage agents. However, due to the difficulty of component extraction and wide variety of ginsenoside, the identification of active antiphotoaging ginsenoside remains a huge challenge. In this study, we proposed a novel in silico approach to identify potential compound against photoaging from 82 ginsenosides. Specifically, we calculated the shortest distance between unknown and known antiphotoaging ginsenoside set in the chemical space and applied chemical structure similarity assessment, drug-likeness screening, and ADMET evaluation for the candidates. We highlighted three rare minor ginsenosides (C-Mc, Mx, and F2) that possess high potential as antiphotoaging agents. Among them, C-Mc deriving from American ginseng (Panax quinquefolius L.) was validated by wet-lab experimental assays and showed significant antioxidant and cytoprotective activity against UVB-induced photodamage in human dermal fibroblasts. Furthermore, system pharmacology analysis was conducted to explore the therapeutic targets and molecular mechanisms through integrating global drug-target network, high quality photoaging-related gene profile from multiomics data, and skin tissue-specific expression protein network. In combination with in vitro assays, we found that C-Mc suppressed MMP production through regulating the MAPK/AP-1/NF-κB pathway and expedited collagen synthesis via the TGF-ß/Smad pathway, as well as enhanced the expression of Nrf2/ARE to hold a balance of endogenous oxidation. Overall, this study offers an effective drug discovery framework combining in silico prediction and in vitro validation, uncovering that ginsenoside C-Mc has potential antiphotoaging properties and might be a novel natural agent for use in oral drug, skincare products, or functional food.