Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.

Clinical Evaluation of a Topical Unani Polyherbal Formulation in the Management of Photodamaged Facial skin: An open-label Standard Controlled Trial.

Introduction: Ageing is a natural process of life. With increasing age, the skin suffers progressive morphological and physiological decrement. Hyperpigmentation, Wrinkles, and roughness of skin are some of the symptoms of aged skin. Exposure to sunlight, pollution, stress, nicotine, etc aggravates Skin aging. This study aimed to determine the efficacy and safety of polyherbal formulation and compare its efficacy with the standard drug tretinoin in subjects of moderate to advanced Photoaged facial skin. Ingredients of polyherbal formulation are Aarade baqla (Vicia faba), Jau (Hordeum vulgare), Nakhud (Cicer arietinum),Masoor (Lens esculenta), Tukhm e turb (Raphanus sativus), Khardal (Brassica nigra), Haldi (Curcuma longa), Kateera (Cochlospermum religiosum). Methods: This was a randomized open-label standard controlled study. 82 eligible subjects were allocated equally into test and control groups by computer-generated random numbers. In the test group, a paste of 15 gm polyherbal formulation in milk, and the control group, 0.025% Tretinoin 1 gram was used topically on the face once a day for two months. The response was assessed by theclinician using following different scales for different parameters. Assessment of Skin hyperpigmentation: It was assessed by the Skin Hyperpigmentation Index online calculator (SHI). It describes the ratio of two scores, namely the hyperpigmented skin of the affected area and normal sun-protected skin from the same patient. The image was recorded with a Digital microscope-Win7 from a hyperpigmented area and normal sun-protected area. Both the images were uploaded on https://shi.skinimageanalysis.com/ and calculated the mean value of hyperpigmentation. SHI ranges from 1 (no hyperpigmentation) to 4 (maximum hyperpigmentation) where scores between 1 and 2 showed as light hyperpigmentation, 2-3 as medium hyperpigmentation, and scores between 3 and 4 as severe hyperpigmentation. Assessment of Fine wrinkles: Fine wrinkles number was determined by digital photography. The photographs were taken through Canon EOS 1500D DSLR Camera with an 18-55 mm Lens. Three images were taken of each subject's face (right, left, and center full face) on Baseline and Day 15th, 30th, 45th, and 60th to assess visible changes/improvement in their fine wrinkles score. Assessment of Nasolabial Fold: Modified Fitzpatrick Wrinkle Scale (MFWS) was used to assess Nasolabial folds. The scale comprised four main classes of Nasolabial wrinkling: 0, 1, 2, and 3 representing absent, fine, moderate, and deep wrinkles, respectively, and three inter classes i.e., 0.5, 1.5, and 2.5 to estimate wrinkle depth. The definitions of the entire classes of the scale are as follows: Class 0 = No wrinkle. No visible wrinkle; continuous skin line; Class 0.5 = Very shallow yet visible wrinkle; Class 1= Fine wrinkle. Visible wrinkle and slight indentation; Class 1.5= Visible wrinkle and clear indentation. <1-mm wrinkle depth; Class 2= Moderate wrinkle. Visible wrinkle, 1- to 2-mm wrinkle depth; Class 2.5= Prominent and visible wrinkle. More than 2-mm and less than 3-mm wrinkle depth; Class 3=Deep wrinkle. Deep and furrow wrinkle; more than 3-mm wrinkle depth. Assessment of Forehead lines score: Forehead lines were assessed (number and depth) by a Validated Grading Scale for Forehead Lines. The Forehead Lines Grading Scale is a 5- point photonumeric rating scale that was developed to objectively quantify resting (static) and hyperkinetic (dynamic) forehead lines. The scale ratings are 0 for no wrinkles, 1 for no wrinkles present at rest but fine lines with facial expression, 2 for fine wrinkles present at rest and deep lines with facial expression, 3 for fine wrinkles present at rest and deeper lines with facial expression, and 4 for deeper wrinkles at rest and deeper furrows with facial expression. Assessment of lateral canthal lines: The number of lateral canthal lines was determined by a Validated Grading Scale for Crow's Feet. The Crow's Feet Grading Scale is a 5- point photonumeric rating scale developed to objectively quantify the severity of crow's feet. This scale was applied to two separate evaluations of crow's feet: at rest (static) and with expression (dynamic). The scale ratings are 0 for no wrinkles, 1 for very fine wrinkles, 2 for fine wrinkles, 3 for moderate wrinkles, and 4 for severe wrinkles. Assessment of Facial Skin Roughness: The Allergan Skin Roughness Scale was used for facial skin roughness assessment. The area of assessment for the Allergan Skin roughness Scale is the area between the nasolabial fold to the preauricular cheek and from the inferior orbital rim to the mandible. The Allergan Skin Roughness Scale assigns a grade from none (0) to extreme (4) that describes the severity of skin coarseness, crosshatching, and elastosis in the midface area. The scale grading are 0 (None) Smooth visual skin texture, 1 (Minimal) Slightly coarse and uneven visual skin texture, 2 (Moderate) Moderately coarse and uneven visual skin texture; may have early elastosis, 3 (Severe) Severely coarse visual skin texture, cross-hatched fine lines; may have some elastosis, and 4 (Extreme) Extremely coarse visual skin texture, cross Hatched deep creases; extreme elastosis. Assessment of Facial Dullness: Dullness was assessed on a clinical basis with an arbitrary scoring ranging from 0 to 9 where 0-3=mild, 3.5-6=moderate, and 6.5-9=severe facial skin dullness. Assessment of quality of life: Subjects' life quality was assessed by the Dermatology Life Quality Index questionnaire. It consists of 10 questions. Each question is scored on a four-point Likert scale: Very much = 3, A lot = 2, A little = 1, Not at all = 0, Not relevant = 0 and Question unanswered = 0. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. Where, 0-1= no effect at all on patient's life, 2-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life. Results: Both groups showed a significant improvement in Fine Wrinkles, Forehead Lines, Crow's Feet, Roughness, Dullness, Nasolabial Fold, Hyperpigmentation, and Quality of Life parameters. (P < .001) A large number of subjects in the control group reported mild to moderate redness, itching, dryness, and blackening of the skin, while in the test group, absolutely no side effects were reported during treatment. Conclusion: The effects in both groups were substantial, but the polyherbal formulation is safe and effective for use in photoaged facial skin. It may be a more feasible easily accessible cheap and safe formulation to prevent skin aging and restore skin elasticity and make skin brighter. Further studies to evaluate the efficacy of formulation on objective parameters using standard instruments should be done for appropriate measurements of parameters.

Dendrobium officinale flowers' topical extracts improve skin oxidative stress and aging.

BACKGROUND: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. OBJECTIVE: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model. METHODS: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. RESULTS: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC50 is 0.2090 µg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. CONCLUSION: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.

An upcycled fraction of Melaleuca alternifolia essential oil regenerates the skin through the skin melatonin pathway and improves sleep quality.

BACKGROUND: Sleep is one of the most important factors affecting overall health. During the night, the skin repairs damage caused by daily stresses. Melatonin plays a key role in this process. Toxins are removed, and cellular repair and growth hormone production are increased. Inter alia, this also decreases signs of intrinsic aging. AIMS: The current study was intended to demonstrate the impact of a unique fraction of Melaleuca alternifolia (FMA) essential oil, on sleep and skin quality. METHODS: The effect of FMA was investigated in vitro on skin cells, evaluating its antioxidant and anti-inflammatory properties, and in an ex-vivo study on human skin biopsies treated with FMA following stress induction. In addition, two clinical studies were performed on volunteers with life-style-related sleep complaints. In one study, sleep was measured using a noncontact monitoring device (SleepScore Labs, Max). A second study was conducted to assess skin anti-aging effects. RESULTS: In vitro application of FMA reduced IL-8 and reactive oxygen species (ROS) generation in skin cells. This was confirmed ex vivo through a decrease in inflammatory markers and an increase in antioxidant enzymes after stress induction. Interestingly, FMA also upregulated melatonin-associated genes. Real-world sleep tracking revealed that FMA significantly improved sleep quality, relative to unscented control. In vivo applications also showed a reduction in signs of aging. CONCLUSION: These results provide initial data to suggest that this unique FMA delivers skin anti-aging benefits via a two-pronged mode of action, improving sleep quality, and reducing skin inflammatory and oxidative stress.

The effects of Jawoongo soap on skin improvement.

BACKGROUND: Jawoongo is used to treat and prevent skin issues such as dry and keratinization disorders, burns, trauma, pigmentation, scarring, and inflammatory skin conditions. In this study, the efficacy and safety of 0.47% Jawoongo extract-containing soap (JAUN-CS) were assessed in terms of skin improvement effects such as cleansing, moisturizing, sebum secretion management, and skin elasticity enhancement. METHODS: Twenty healthy adult men and women aged 20-60 years old took part in the study. Before and after using JAUN-CS, the participants were divided into groups, and various skin improvement effects were measured utilizing machines such as the Corneometer, Tewameter TM 300, and Visioscan. A dermatologist analyzed the product's safety in accordance with Frosch & Kligman and the Cosmetic, Toiletry, and Fragrance Association (CTFA) rules. RESULTS: Using JAUN reduced the amount of base and point makeup by 25.7% and 76.7%, respectively. Also, JAUN showed a great facial exfoliation effect by removing the old and lifted skin keratins by 84.7% and 20.3%, respectively. Impurities in facial pores decreased by 58%, too. Furthermore, JAUN increased the moisture content of deep skin and skin surface by 3.5% and 74.0%, and skin elasticity by 2.8%. Skin tone, skin texture, skin radiance, and skin barrier all showed improvements of 3.3%, 20.0%, 15.0%, and 115.2%, respectively. Lastly, cleansing with JAUN successfully enhanced the condition of the youth triangle by 7.6%, while TEWL significantly decreased by 52.7%. Neither the JAUN nor the control group soap showed any adverse reactions, such as erythema or allergies, during the testing period. CONCLUSIONS: The results of this study demonstrated that JAUN is safe for human use and has various skin-improving properties, making Jawoongo a promising natural material for the development of functional cosmetics in the future.

Oroxylin A ameliorates ultraviolet radiation-induced premature skin aging by regulating oxidative stress via the Sirt1 pathway.

Skin is susceptible to premature aging in response to ultraviolet (UV) radiation-induced oxidative stress, which can ultimately result in aberrant aging or age-related disorders. Accordingly, strategies that can be adopted to mitigate oxidative stress may contribute to protecting skin from induced aging-related damage, thereby offering promising approaches for the treatment of skin diseases and disorders. In this regard, oroxylin A (OA), a natural flavonoid isolated from certain plants used in traditional Chinese medicine, is considered to have notable antioxidant, anti-inflammatory, and anti-apoptotic properties, and is often used to treat certain inflammatory diseases. To date, however, there has been comparatively little research on the effects of OA with respect skin aging. In this study, we utilized UV radiation-induced mouse and cellular models of aging to assess the efficacy of OA in protecting against skin aging. Subsequently, to elucidate the potential mechanisms underlying the protective effect of OA on skin aging, we performed molecular docking analysis to investigate the involvement of the anti-aging gene Sirt1, which was further confirmed on the basis of Sirt1 gene silencing. We accordingly demonstrated that by promoting an increase in the expression of Sirt1, OA can contribute to suppressing UV-induced skin photo-aging in cells/mice by reducing oxidative stress. Furthermore, we established that by activating Sirt1, OA can also promote the dissociation of Nrf2 from Keap1 and its subsequent nuclear translocation. Collectively, our findings in this study reveal OA to be an effective natural compound that can be administered to delay the aging of skin triggered by UV, both in vivo and in vitro, by binding to Sirt1 to promote the deacetylation and nuclear translocation of Nrf2, thereby contributing to a reduction in oxidative stress. These findings may this provide a therapeutic target for the prevention of skin aging or aging-induced skin diseases.

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Characterization and anti-aging effects of Opuntia ficus-indica (L.) Miller extracts in a D-galactose-induced skin aging model.

Opuntia ficus-indica (L.) Miller (OFI), belonging to the family Cactaceae, is widely cultivated not only for its delicious fruits but also for its health-promoting effects, which enhance the role of OFI as a potential functional food. In this study, the in vitro collagenase and elastase enzyme inhibitory effects of extracts from different parts of OFI were evaluated. The most promising extracts were formulated as creams at two concentrations (3 and 5%) to investigate their effects on a D-galactose (D-gal)-induced skin-aging mouse model. The ethanolic extracts of the peel and cladodes exhibited the highest enzyme inhibitory effects. Cream made from the extract of OFI peel (OP) (5%) and cream from OFI cladodes extract (OC) (5%) significantly decreased the macroscopic aging of skin scores. Only a higher concentration (5%) of OC showed the normalization of superoxide dismutase (SOD) and malondialdehyde (MDA) skin levels and achieved significant improvements as compared to the vitamin E group. Both OC and OP (5%) showed complete restoration of the normal skin structure and nearly normal collagen fibres upon histopathological examination. The Ultra-Performance Liquid Chromatography High Resolution Mass Spectrometry (UHPLC-ESI-TOF-MS) metabolite profiles revealed the presence of organic acids, phenolic acids, flavonoids, betalains, and fatty acids. Flavonoids were the predominant phytochemical class (23 and 22 compounds), followed by phenolic acids (14 and 17 compounds) in the ethanolic extracts from the peel and cladodes, respectively. The anti-skin-aging effects could be attributed to the synergism of different phytochemicals in both extracts. From these findings, the OFI peel and cladodes as agro-waste products are good candidates for anti-skin-aging phytocosmetics.

Uso de hidroxiapatita de cálcio no tratamento da dermatoporose / Use of calcium hydroxyapatite in the treatment of dermatoporosis

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.

Rosa davurica inhibits skin photoaging via regulating MAPK/AP-1, NF-κB, and Nrf2/HO-1 signaling in UVB-irradiated HaCaTs.

Rosa davurica is widely used to treat various kinds of diseases because of its high antioxidant, antiviral and anti-inflammatory activities. This use of plant-based materials as medicine is called phytomedicine and has been widely practiced since time immemorial. However, the pharmacological mechanism of R. davurica in skin photoaging is not yet fully understood. Therefore, this study was carried out to evaluate the recovery effects of R. davurica leaf extracts (RDE) in UVB-irradiated human skin keratinocytes (HaCaTs) and investigate whether RDE is a potential therapeutic agent against skin photoaging. The expression of aging-related markers including mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1), nuclear factor-κB (NF-κB), and nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was evaluated using Western blot analysis. The reactive oxygen species (ROS) was also used by FACS in HaCaTs. Findings indicated that RDE is efficient in scavenging free radicals and dose-dependently reducing ROS generation. Furthermore, RDE notably decreased UVB-induced matrix metalloproteinase-1 (MMP-1) expression through inhibition of MAPK/AP-1 and NF-κB signaling pathways as well as induced blocking of extracellular matrix (ECM) degradation in UVB-irradiated HaCaTs. In addition, RDE improved Nrf2/HO-1 signaling that increases oxidative defense capacity and enhances transforming growth factor-beta (TGF-ß) signaling activation to promote procollagen type I synthesis, relieving UVB-induced skin cell damage. In conclusion, the protective effects of RDE on skin cellular components suggest that it has a high biological potential for skin protection from UVB-induced skin photoaging and is a good candidate for drug and cosmetic application.

Umbilicaria esculenta Extract Exhibits Antiwrinkle Activity by Suppressing ErbB2 Phosphorylation.

Umbilicaria esculenta (UE), an edible lichen, is widespread in northeast Asian countries, including China, Japan, and Korea. In the present study, we examined the antiwrinkle activity of UE. We observed that the UE extract (UEE) suppressed ultraviolet (UV)-induced matrix metalloprotein-1 (MMP-1) expression and reactive oxygen species (ROS) generation in a human keratinocyte cell line (HaCaT) and human skin tissue. In addition, UEE reversed the UV-induced decrease in collagen in the human skin tissue. Excessive and chronic UV exposure is a key factor underlying skin wrinkle formation via MMP-1 expression. As treatment with UEE disrupted the UV-activated mitogen-activated protein kinase (MAPK) signaling pathway, we applied an antibody array to unveil the underlying mechanism of UEE. Interestingly, UEE treatment inhibited ErbB2 phosphorylation, but not epidermal growth factor receptor phosphorylation, a heterodimerization partner with ErbB2. Furthermore, UEE treatment enhanced UV-suppressed phosphatase activity via ROS suppression. Collectively, our findings indicate that UEE enhances ErbB2 dephosphorylation to suppress UV-induced MMP-1 expression.

Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via Nrf2 pathway.

Excessive exposure to ultraviolet B (UVB) irradiation is one of the major risk factors for skin photoaging. The aim of this study was to investigate the protective effect of Premna microphylla Turcz pectin (PMTP) against UVB-induced skin aging in BALB/c-nu mice. PMTP was characteristic of a low methoxyl RG-I pectin with Mw was 26.60 kDa, mainly composed of galacturonic acid. PMTP-containing cream efficiently inhibited the water loss, epidermal hyperplasia, matrix metalloproteinases-1 (MMP-1), and collagen destruction in UVB-induced skin injury mice. Additionally, topical administration of PMTP-containing cream significantly increased protein levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), macrophage-activating factor (Maf), and heme oxygenase 1 (HO-1), and the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In contrast, application of PMTP-containing cream on mice skin decreased the protein levels of nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase ß (IKKß), and cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines. Taken togethmier, these findings suggest that PMTP might protect UVB-induced skin aging via activating Nrf2 pathway and suppressing NF-κB pathway.

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.

Dual Skin-Whitening and Anti-wrinkle Function of Low-Molecular-Weight Fish Collagen.

In this study, we investigated the protective effects of low-molecular-weight fish collagen from tilapia against melanogenesis in melanocytes, ultraviolet B (UVB)-irradiated Hs27 skin fibroblasts, and hairless mice. We observed collagen production-related pathways in UVB-irradiated Hs27 skin fibroblasts and hairless mice, and the melanogenesis-related pathways in melanocyte and UVB-irradiated hairless mice. The collagen production-related pathways were activated in the UVB-irradiated Hs27 skin fibroblasts and hairless mice. In addition, UVB exposure stimulated the melanogenesis-related pathways in melanocytes and hairless mice. However, treatment with low-molecular-weight fish collagen significantly increased the messenger RNA expressions of collagen production-related factors and significantly decreased the production of cytokines. Furthermore, treatment with low-molecular-weight fish collagen suppressed melanogenesis by inhibiting glutathione synthesis and downregulating melanocyte-inducing transcription factor expression through the suppression of cyclic AMP/protein kinase A/cAMP-responsive binding protein signaling and nitric oxide production. Low-molecular-weight fish collagen exerts protective effects against UVB-induced photoaging, through anti-inflammatory, antioxidant, and anti-melanogenesis activities and could be used for developing effective natural anti-photoaging products.

Bioactive-Based Cosmeceuticals: An Update on Emerging Trends.

Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.

Validation of a High-Performance Liquid Chromatography with Photodiode Array Detection Method for the Separation and Quantification of Antioxidant and Skin Anti-Aging Flavonoids from Nelumbo nucifera Gaertn. Stamen Extract.

Nelumbo nucifera Gaertn., or the so-called sacred lotus, is a useful aquatic plant in the Nelumbonaceae family that has long been used to prepare teas, traditional medicines as well as foods. Many studies reported on the phytochemicals and biological activities of its leaves and seeds. However, to date, only few studies were conducted on its stamen, which is the most important ingredient for herbal medicines, teas and other phytopharmaceutical products. Thus, this present study focuses on the following: (1) the application of high-performance liquid chromatography with photodiode array detection for a validated separation and quantification of flavonoids from stamen; (2) the Nelumbo nucifera stamen's in vitro and in cellulo antioxidant activities; as well as (3) its potential regarding the inhibition of skin aging enzymes for cosmetic applications. The optimal separation of the main flavonoids from the stamen ethanolic extract was effectively achieved using a core-shell column. The results indicated that stamen ethanolic extract has higher concentration of in vitro and in cellulo antioxidant flavonoids than other floral components. Stamen ethanolic extract showed the highest protective effect against reactive oxygen/nitrogen species formation, as confirmed by cellular antioxidant assay using a yeast model. The evaluation of potential skin anti-aging action showed that the stamen extract has higher potential to inhibit tyrosinase and collagenase compared with its whole flower. These current findings are the first report to suggest the possibility to employ N. nucifera stamen ethanolic extract as a tyrosinase and collagenase inhibitor in cosmetic applications, as well as the utility of the current separation method.

Trehangelins ameliorate inflammation-induced skin senescence by suppressing the epidermal YAP-CCN1 axis.

Trehangelins (THG) are newly identified trehalose compounds derived from broth cultures of an endophytic actinomycete, Polymorphospora rubra. THG are known to suppress Cellular Communication Network factor 1 (CCN1), which regulates collagen homeostasis in the dermis. Although the physical properties of THG suggest a high penetration of the stratum corneum, the effect of THG on the epidermis has not been reported. Here we describe a possible mechanism involved in skin aging focusing on the effect of THG on epidermal CCN1. This study shows that: (1) THG suppress epidermal CCN1 expression by inhibiting the translocation of Yes-Associated Protein (YAP) to nuclei. (2) Epidermal CCN1, localized at the basement membrane, regulates the balance between the growth and differentiation of keratinocytes. (3) Keratinocytes secrete more CCN1 than fibroblasts, which leads to disruption of the basement membrane and extracellular matrix components. (4) The secretion of CCN1 from keratinocytes is increased by ultraviolet B exposure, especially in aged keratinocytes, and deteriorates the elastic fiber structures in the underlying dermis. (5) Topical application of THG ameliorates the structure of the basement membrane in ex vivo human skin explants. Taken together, THG might be a promising treatment for aged skin by suppressing the aberrant YAP-CCN1 axis.

Evaluation and enzyme-aided enhancement of anti-photoaging properties of Camellia japonica in UVA-irradiated keratinocytes.

Exposure to ultraviolet (UV) radiation is the main reason behind extrinsic skin aging. Changes due to chronic UV exposure are called photoaging. Natural products are effective ingredients against UV-mediated skin damage. Present study investigated the anti-photoaging properties of Camellia japonica flowers which possess various bioactivities. To enrich the extracts of C. japonica flowers, pectinase and beta-glucosidase treatment was employed. Anti-photoaging effect was screened using the changes in MMP-1 and collagen levels in UVA-irradiated human HaCaT keratinocytes. The crude extract of C. japonica flowers (CE) was shown to decrease the UVA-induced MMP-1 secretion while attenuating the collagen levels. Pectinase and beta-glucosidase treated CE (ECE) showed increased anti-photoaging effects against UVA-induced changes in MMP-1 and collagen production. Camellenodiol (CMD), a known triterpenoid from C. japonica, isolated as the active ingredient of ECE and its anti-photoaging effect was screened. Results showed that CMD ameliorated the UVA-induced deterioration in collagen levels by suppressing MMP-1 production in transcriptional level. CMD treatment downregulated the phosphorylation of p38, ERK, and JNK MAPKs along their downstream effectors, c-Fos, and c-Jun. In conclusion, enzyme-assisted extraction of C. japonica flowers was suggested to enhance the anti-photoaging properties suggestively through high bioactive content such as CMD.

Comparison of chemical profiles, antioxidation, inhibition of skin extracellular matrix degradation, and anti-tyrosinase activity between mycelium and fruiting body of Cordyceps militaris and Isaria tenuipes.

CONTEXT: Cordyceps militaris and Isaria tenuipes (Cordycipitaceae) are high-value fungi that are used for health-promoting food supplements. Since laboratory cultivation has begun for these fungi, increased output has been achieved. OBJECTIVE: This study compared the chemical profiles, antioxidant, anti-tyrosinase, and skin extracellular matrix degradation inhibition between mycelium and fruiting body of C. militaris and I. tenuipes. MATERIALS AND METHODS: The antioxidative potential of 10% v/v aqueous infused extract from each fungus was separately investigated using 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant ability, and ferric thiocyanate methods. The inhibition against MMP-1, elastase, and hyaluronidase were determined to reveal their anti-wrinkle potential. Anti-tyrosinase activities were determined. RESULTS: C. militaris and I. tenuipes extracts were found to contain a wide range of bioactive compounds, including phenolics, flavonoids, and adenosine. A correlation was discovered between the chemical compositions and their biological activities. The extract from I. tenuipes fruiting body (IF) was highlighted as an extraordinary elastase inhibitor (IC50 = 0.006 ± 0.004 mg/mL), hyaluronidase inhibitor (IC50: 30.3 ± 3.2 mg/mL), and antioxidant via radical scavenging (ABTS IC50: 0.22 ± 0.02 mg/mL; DPPH IC50: 0.05 ± 0.02 mg/mL), thereby reducing ability (EC1: 95.3 ± 4.8 mM FeSO4/g extract) and lipid peroxidation prevention (IC50: 0.40 ± 0.11 mg/mL). IF had a three-times higher EC1 value than ascorbic acid and significantly higher elastase inhibition than epigallocatechin gallate. DISCUSSION AND CONCLUSIONS: IF is proposed as a powerful natural extract with antioxidant and anti-wrinkle properties; therefore, it is suggested for further use in pharmaceutical, cosmeceutical, and nutraceutical industries.