Oroxylin A ameliorates ultraviolet radiation-induced premature skin aging by regulating oxidative stress via the Sirt1 pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
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.
10.1016/j.biopha.2023.116110
The combined effect of commercial tilapia collagen peptides and antioxidants against UV-induced skin photoaging in mice.
Food & function
Chronic over-exposure to UV radiation leads to the damage of skin tissue. The aim of this study was to investigate the effects of collagen peptide (CP) and antioxidant (astaxanthin, vitamin C (Vc), and vitamin E (Ve)) combinations on skin photoaging. Forty male UV-induced BALB/c mice were randomized and fed saline or CP and antioxidants for 7 weeks using gavage feeding. The results showed that oral administration of CP, CP combined with Vc and Ve (VCE) or extract (HPE) significantly ( < 0.05) reduced a* of mouse skin and increased the content of Hyp and type I collagen to varying degrees, thereby improving skin integrity. Furthermore, the combination of CP, HPE, and VCE showed increased upregulation of antioxidant enzyme expression, reduced serum ROS, and decreased inhibition of metalloproteinase expression compared to the other treatment groups. Thus, this combination showed better effects in inhibiting collagen degradation and maintaining the redox balance. The Nrf2/ARE and TGF-β/Smad transcription systems are likely involved in these effects. Therefore, the results suggest that a diet containing CP, astaxanthin, and vitamins might be recommended to improve skin health and appearance.
10.1039/d3fo01516e
Antiwrinkle and Antimelanogenesis Effects of Tyndallized KCCM12625P.
Lim Hye Yeon,Jeong Deok,Park Sang Hee,Shin Kon Kuk,Hong Yo Han,Kim Eunji,Yu Yeong-Gyeong,Kim Tae-Rahk,Kim Hun,Lee Jongsung,Cho Jae Youl
International journal of molecular sciences
UVB irradiation can induce generation of reactive oxygen species (ROS) that cause skin aging or pigmentation. is a well-known probiotic strain that regulates skin health through antimicrobial peptides and organic products produced by metabolism and through immune responses. In this study, we investigated the antioxidative, antiwrinkle, and antimelanogenesis effects of tyndallized KCCM12625P (AL). To analyze the effects of AL on UV irradiation-induced skin wrinkle formation in vitro, human keratinocytes and human dermal fibroblasts were exposed to UVB. Subsequent treatment with AL induced antiwrinkle effects by regulating wrinkle-related genes such as matrix metalloproteinases (MMPs), SIRT-1, and type 1 procollagen (COL1AL). In addition, Western blotting assays confirmed that regulation of MMPs by AL in keratinocytes was due to regulation of the AP-1 signaling pathway. Furthermore, we confirmed the ability of AL to regulate melanogenesis in B16F10 murine melanoma cells treated with α-melanocyte-stimulating hormone (-MSH). In particular, AL reduced the mRNA expression of melanogenesis-related genes such as tyrosinase, TYRP-1, and TYRP-2. Finally, we used Western blotting assays to confirm that the antimelanogenesis role of AL was due to its regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway. Collectively, these results indicate that AL has an antiwrinkle activity in damaged skin and can inhibit melanogenesis. Thus, AL should be considered an important substance for potential use in anti-aging drugs or cosmetics.
10.3390/ijms21051620
Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.
Kalyana Sundaram Induja,Sarangi Deepika Deeptirekha,Sundararajan Vignesh,George Shinomol,Sheik Mohideen Sahabudeen
BMC complementary and alternative medicine
BACKGROUND:Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. METHODS:The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. RESULT:It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. CONCLUSION:Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.
10.1186/s12906-018-2097-9
Prevention of UV-induced skin cancer in mice by gamma oryzanol-loaded nanoethosomes.
Zeinali Mahdi,Abbaspour-Ravasjani Soheil,Soltanfam Tannaz,Paiva-Santos Ana Cláudia,Babaei Hossein,Veiga Francisco,Hamishehkar Hamed
Life sciences
AIMS:Skin cancer is the most widespread cancer worldwide, mainly caused by exposure to ultraviolet radiation (UV) in sunlight. Utilizing topical preventive agents in routinely daily used cosmetics may prevent UV-related skin damages and skin cancers. γ-Oryzanol (GO) is a natural component derived from rice bran oil, with potential antioxidant and skin anti-aging properties. MAIN METHODS:We biologically thorough studied the antioxidant and anticancer effects of GO in vitro to found the effective signaling pathways, then evaluated the sun protection factor of prepared formulation, and finally investigated the long-term preventive effects of GO-loaded nanoethosomes (GO-NEs) against UVB-induced skin cancer in mice. KEY FINDINGS:GO-NEs could effectively prevent UVB-induced skin cancer. SIGNIFICANCE:Our results suggest that GO-NEs could be utilized as an innovative ingredient in cosmetics.
10.1016/j.lfs.2021.119759
Cosmeceutical effect on skin surface profiles and epidermis in UV-B-irradiated mice.
Bhattacharyya Tapan K,Pathria Mohini,Mathison Clyde,Vargas Maria,Thomas J Regan
JAMA facial plastic surgery
IMPORTANCE:These data may be useful for developing guidelines for clinicians and the general population related to the reversal of photoaging effects on the aging face damaged by solar radiation. OBJECTIVE:To investigate antiaging effects of 4 commercially available topical agents on the dorsal skin in photoaged hairless mice. DESIGN AND SETTING:Animal study at an academic medical center. Animals comprised 56 female Skh-1 hairless mice (6-8 weeks old). Skin samples were collected from nonirradiated intact mice (control), mice irradiated with UV-B for 8 weeks, mice irradiated with UV-B and then exposed to a topical cosmeceutical applied for 5 weeks, and UV-B-irradiated mice not exposed to cosmeceuticals and retained for 5 weeks until the end of the experiment. INTERVENTION:The mice were exposed to UV-B light 3 times a week for 2 months, followed by topical application of a peptide, antioxidant, estrogen, and retinoic acid agent for 5 weeks. MAIN OUTCOMES AND MEASURES:Surface features such as wrinkling were analyzed from replicas along with histomorphometric determination of epidermal thickness, sebocyte counts, and immunohistochemical study of proliferating cell nuclear antigen (PCNA). RESULTS:Exposure to UV-B induced significant wrinkle formation after 13 weeks, which was attenuated with treatments with a peptide cream, antioxidant mixture, and estrogen cream (mean [SD] Rz values: control [C], 60.7 [19.0]; irradiated [RAD], 51.8 [15.9] [P < .001]; irradiated-long [RAD-long], 86.0 [28.3] [P = .01]; antioxidant [AO], 45.2 [13.2]; peptide, 63.4 [18.8], estrogen, 64.6 [21.2]; retinoic acid [RA], 73.9 [28.5]; RAD-long vs C [P = .01], vs RAD [P < .001], vs estrogen [P = .04], vs peptide [P = .02], vs AO [P<.001], vs RA [P = .25]. There was a trend of reversal of irradiation-induced augmentation of epidermal thickness in animals treated with the peptide and AO (mean [SD] epidermal width: C, 21.0 [2.2] μm; RAD, 41.3 [7.0] μm [P < .001]; RAD-long, 39.1 [11.0] μm [P = .006]; AO, 37.3 [14] μm [P < .001]; peptide, 33.9 [3.8] μm [P = .01]; estrogen, 59.2 [9.2] μm [P = .003]; RA, 52.4 [8.7] μm [P < .001]). Retinoic acid augmented epidermal width and sebocyte counts (mean [SD] sebocyte data [number per gland]: C, 9.4 [2.0]; RAD, 11.69 [1.5] [P < .001]; RAD-long, 6.5 [1.3] [P = .73]; peptide, 7.2 [1.7] [P = .03]; estrogen, 4.1 [0.9] [P < .001]; AO, 7.2 [1.7] [P = .06]; RA, 11.0 [1.4] [P = .01]). Estrogen cream was effective in restoring surface features but enhanced thickness of epidermis in irradiated specimens. All groups had a higher PCNA index score except for peptide treatment, which brought it down to the control level (mean [SD] PCNA index values: C, 17.3 [1.5]; RAD, 32.4 [6.8] [P < .001]; RAD-long, 34.0 [6.1] [P < .001]; AO, 62.1 [3.5] [P = .01]; peptide, 20.1 [6.3] [P < .001]; estrogen, 56.8 [10.0] [P < .001]; RA, 35.2 [10.2] [P < .001]). CONCLUSIONS AND RELEVANCE:Of the 4 cosmeceuticals tested within this experimental period, peptide cream and antioxidant mixture were the most effective overall in reversing photoaging effects; retinoic acid was the least effective of these topical agents. LEVEL OF EVIDENCE:NA.
10.1001/jamafacial.2013.2582
Effects of irradiance on UVA-induced skin aging.
Lan Cheng-Che E,Hung Yu-Ting,Fang Ai-Hui,Ching-Shuang Wu
Journal of dermatological science
BACKGROUND:Ultraviolet A (UVA) radiation is the most relevant component of solar radiation-induced skin aging. Sunscreens were used to minimize the harmful effects of UV radiation on our skin by reducing UV irradiance. We previously found that at equivalent fluence, UVB radiation at low irradiance (LI) has higher photocarcinogenic potential as compared to its high irradiance (HI) counterpart. OBJECTIVES:To examine the effects of equivalent fluence of UVA radiation administered at different irradiance on photoaging. METHODS:Both the hairless mice (SKH-1) and human dermal fibroblasts were irradiated with high irradiance UVA (HIUVA) or low irradiance UVA (LIUVA; 50% irradiance of HIUVA) at equivalent fluence. Parameters related to skin photoaging were evaluated. RESULTS:For hairless mice receiving equivalent fluence of UVA radiation, LIUVA treated mice showed prominent skin aging as compared to its HIUVA treated counterpart. In addition, LIUVA radiation induced higher reactive oxygen species (ROS) production and c-Jun N-terminal kinases (JNK) phosphorylation as compared to their HIUVA treated counterparts. Pretreatment with N-acetylcysteine (NAC) abrogate the difference between HI and LIUVA radiation on fibroblasts in terms of intracellular ROS, JNK phosphorylation, MMP-1 expression and type I collagen expression. CONCLUSION:UVA radiation administered at LI (a scenario similar to sunscreen use) led to more severe aging process as compared to its HI counterpart. Unexpected negative effect may be imposed on the skin if sunscreen use is accompanied by longer duration spent under the sun.
10.1016/j.jdermsci.2019.03.005
Skin Biomechanics and miRNA Expression Following Chronic UVB Irradiation.
Blackstone Britani N,Wilgus Traci A,Roy Sashwati,Wulff Brian C,Powell Heather M
Advances in wound care
Exposure to ultraviolet (UV) light from the sun is known to accelerate the skin aging process and leads to significant alterations in skin biomechanics; however, the molecular mechanisms by which chronic UVB affects biomechanical properties of the skin have not been well described. A murine model for chronic UVB exposure was used to examine changes in epidermal barrier function, skin biomechanics, and miRNA expression as a result of UVB. UVB irradiation caused skin to be weaker, less elastic, stiffer, and less pliable. Notably, these changes were not reversed after a 5-week period of recovery. Following UVB exposure, dermal collagen fibrils were significantly smaller in diameter and expression of the miR-34 family was significantly increased. To our knowledge, this is the first study to concurrently examine alterations in skin function, miRNA expression, and tissue biomechanics in response to chronic UVB exposure. The data suggest that UVB alters miR-34 family expression in skin, in addition to dysregulating collagen structure with subsequent reductions in strength and elasticity. miRNAs may play a pivotal role in regulating extracellular matrix deposition and skin biomechanics following chronic UVB exposure, and thus may be a possible target for therapeutic development. However, additional studies are needed to directly probe the link between UVB exposure, miRNA production, and skin biomechanics.
10.1089/wound.2019.1034
Caviar Extract and Its Constituent DHA Inhibits UVB-Irradiated Skin Aging by Inducing Adiponectin Production.
Lee Kyung-Eun,Nho Youn-Hwa,Yun Seok Kyun,Park Sung-Min,Kang Seunghyun,Yeo Hyeonju
International journal of molecular sciences
In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid components of caviar extract, induces intracellular lipid accumulation and the expression of adiponectin in adipocytes. Although adipocytes are well known to be associated with the skin dermis by secreting various factors (e.g., adiponectin), the effects of caviar extract and DHA on the skin are not well studied. Here, we demonstrate the effects of caviar extract and DHA on adipocyte differentiation and adiponectin production, resulting in a preventive role in UV-irradiated skin aging. Caviar extract and DHA enhanced adipocyte differentiation and promoted the synthesis of transcription factors controlling adipocyte differentiation and adiponectin. In addition, the mRNA expression levels of matrix metalloproteinase-1 (MMP-1) were decreased in UVB-irradiated Hs68 fibroblasts that were cultured in conditioned medium from caviar extract or DHA-treated differentiated adipocytes. Taken together, these results indicate that caviar extract and DHA induce adipocyte differentiation and adiponectin production, thereby inhibiting UVB-induced premature skin aging via the suppression of MMP-1 production.
10.3390/ijms21093383
Preparation of Cod Skin Collagen Peptides/Chitosan-Based Temperature-Sensitive Gel and Its Anti-Photoaging Effect in Skin.
Drug design, development and therapy
Background:Photoaging decreases quality of life and increases the risk of skin cancer, underscoring the urgent need to explore natural, high-efficacy, anti-skin photoaging (SP) active substances. Methods:In this study, a gel (CS/CSCPs/β-GP gel) was prepared using chitosan (CS) and sodium β-glycerophosphate (β-GP) through crosslinking with small molecular CSCPs as the carried drug. We evaluated its structural characteristics and properties. The effect of CS/CSCPs/β-GP gel on the degree of ultraviolet (UV)-induced skin aging of mice was investigated through comparative analysis of skin damage, the integrity of collagen tissues and elastic fibers, levels of reactive oxygen species (ROS) and key inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1β, IL-6, and IL-10), and tissue expression of matrix metalloproteinase-3 (MMP-3) after repeated UV irradiation in a nude mice SP model. Results:The results showed that CS/CSCPs/β-GP gel was successfully prepared and had the desired characteristics. Compared with CSCPs alone, the CS/CSCPs/β-GP gel more evidently improved typical photoaging characteristics on mouse dorsal skin. It also increased the moisture content, causing the skin to become glossy and elastic. Pathological skin analysis revealed that this peptide-carrying gel can effectively inhibit epidermal thickening, reduce tissue inflammatory infiltration, suppress collagen fiber degradation, increase the collagen content, alleviate structural elastic fiber damage, and significantly inhibit abnormal MMP-3 expression. In addition, biochemical analysis showed that the CS/CSCPs/β-GP gel can effectively inhibit the elevated expressions of ROS and key proinflammatory factors (TNF-α, IL-1β, IL-6) in photoaging skin tissues and promote expression of the anti-inflammatory factor IL-10. Conclusion:SP can cause many clinical skin diseases, such as solar freckle-like nevus, solar keratosis, cutaneous melanoma, and squamous cell carcinoma. CSCPs are a high-efficacy anti-SP natural active substance and CS/CSCPs/β-GP gel can synergistically enhance the CSCPs' anti-SP effect. The mechanism is likely related to the inhibited activation of ROS/nuclear transcription factor-κB signaling and the expression of downstream inflammatory factors.
10.2147/DDDT.S391812
HucMSC exosome-delivered 14-3-3ζ alleviates ultraviolet radiation-induced photodamage via SIRT1 pathway modulation.
Wu Peipei,Zhang Bin,Han Xinye,Sun Yaoxiang,Sun Zixuan,Li Linli,Zhou Xinru,Jin Qian,Fu Peiwen,Xu Wenrong,Qian Hui
Aging
Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) are nano-sized membrane-bound vesicles that have been reported to facilitate skin regeneration and repair. However, the roles played by hucMSC-ex in ultraviolet (UV) radiation-induced skin photodamage and the underlying mechanisms remain unknown. To investigate the functions of hucMSC-ex in a rat model of acute skin photodamage, immunofluorescence and immunohistochemical staining, quantitative real-time-polymerase chain reaction (qRT-PCR), western blot, and gene silencing assays were performed. We found that the subcutaneous injection of hucMSC-ex elicited antioxidant and anti-inflammatory effects against UV radiation-induced DNA damage and apoptosis. Further studies showed that the sirtuin 1 (SIRT1) expression level in skin keratinocytes (HaCaT) decreased in a time- and dose-dependent manner under UV radiation induced-oxidative stress conditions, which could be reversed by treatment with hucMSC-ex. The activation of SIRT1 significantly attenuated UV- and HO-induced cytotoxic damage by inhibiting oxidative stress and promoting the activation of autophagy. Our study found that 14-3-3ζ protein, which was delivered by hucMSC-ex, exerted a cytoprotective function via the modulation of a SIRT1-dependent antioxidant pathway. Collectively, our findings indicated that hucMSC-ex might represent a new potential agent for preventing or treating UV radiation-induced skin photodamage and aging.
10.18632/aging.202851
Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice.
Molecules (Basel, Switzerland)
BACKGROUND:Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. METHODS:Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. RESULTS:Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFα, and decreased keratinocyte damage. CONCLUSION:Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.
10.3390/molecules28072929
Antioxidant cinnamaldehyde attenuates UVB-induced photoaging.
Tanaka Yuka,Uchi Hiroshi,Furue Masutaka
Journal of dermatological science
BACKGROUND:Ultraviolet (UV) irradiation disrupts skin through several deleterious actions, such as induction of reactive oxygen species (ROS), DNA damage, and collagen degradation. Cinnamaldehyde (CIN) is a major constituent of the cinnamon and it possesses potent antioxidative activity; however, it is unclear whether CIN is capable of inhibiting the adverse effects of UVB. OBJECTIVE:To investigate protective effects of CIN against UVB-induced photodamage. METHODS:HaCaT keratinocytes were pretreated with CIN, irradiated with UVB, and assessed for the ROS production by flow cytometry and for the DNA damage by ELISA. As in vivo mouse model, Hos:HR-1 hairless mice were treated with ointments containing DMSO or CIN and irradiated multiple times with UVB. After 10 weeks of irradiation, wrinkle formation, epidermal thickness, infiltrating cell number, malondialdehyde amount, collagen amount, MAP kinase signaling, and related gene expressions (Hmox1, Col1a1, Mmp1a, and Mmp13) were analyzed. RESULTS:CIN significantly reduced the ROS production and accelerated the repair of DNA damage pyrimidine(6-4)pyrimidone photoproducts in UVB-irradiated human keratinocytes in vitro. In the mouse model, topical application of CIN significantly inhibited wrinkle formation, epidermal hyperplasia, and dermal inflammatory cell infiltration. The antioxidative process was significantly promoted in the CIN-applied site, as evidenced by upregulation of the antioxidative enzyme Hmox1 as well as the reduced accumulation of malondialdehyde. In addition, topical application of CIN normalized the UVB-induced collagen/Col1a1 downregulation and the UVB-induced Mmp13 upregulation, implying the prevention of UVB-induced collagen degradation. CONCLUSIONS:CIN and CIN-containing herbal agents may exert potent protective effects against UVB exposure on skin.
10.1016/j.jdermsci.2019.11.001
Rosmarinic acid alleviates ultraviolet-mediated skin aging via attenuation of mitochondrial and ER stress responses.
Experimental dermatology
Chronic exposure to Ultraviolet B radiation (UV-B) evokes a myriad of toxic signalling events in the irradiated skin. One of such response is ER stress, which is known to exacerbate photodamage responses. Also, recent literature has highlighted the adverse impact of environmental toxicants on mitochondrial dynamics and mitophagy. Impaired mitochondrial dynamics escalates oxidative damage and causes apoptosis. There have been evidences that support crosstalk between ER stress and mitochondrial dysfunction. However, mechanistic clarification is still needed to verify the interactions between UPR responses and mitochondrial dynamics impairment in UV-B-induced photodamage models. Lastly, plant-based natural agents have garnered attention as therapeutic agents against skin photodamage. Thus, gaining mechanistic insights of plant-based natural agents is required for their application and feasibility in clinical settings. With this aim in view, this study was performed in primary human dermal fibroblasts (HDFs) and Balb/C mice. Different parameters regarding mitochondrial dynamics, ER stress, intracellular damage and histological damage were analyzed using western blot, rt-PCR and microscopy. We demonstrated that UV-B exposure leads to induction of UPR responses, upregulation of Drp-1 and inhibition of mitophagy. Further, 4-PBA treatment leads to reversal of these noxious stimuli in irradiated HDF cells, thereby, indicating an upstream role of UPR induction in mitophagy inhibition. Also, we explored the therapeutic effect of Rosmarinic acid (RA) against ER stress and impaired mitophagy in photodamage models. RA prevents intracellular damage via alleviation of ER stress and mitophagic responses in HDFs and irradiated Balb/C mice skin. The current study summarizes the mechanistic insights into UVB-mediated intracellular damage and role of natural plant-based agent (RA) in ameliorating these toxic responses.
10.1111/exd.14773
YAP1/Piezo1 involve in the dynamic changes of lymphatic vessels in UVR-induced photoaging progress to squamous cell carcinoma.
Journal of translational medicine
BACKGROUND:UV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymphatic-centered immune microenvironment are essential in transforming from photoaging to cSCC. Studying the mechanism will be beneficial for new targets exploration to the early prediction of cSCC. AIMS:To investigate the dynamic changes and mechanism of the lymphatic-centered immune microenvironment in transforming from photoaging to cSCC induced by ultraviolet irradiation (UVR). METHODS:TIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progressed into actinic keratosis and cSCC on SKH-1 hairless mice. The skin lymphatic-centered immune microenvironment was evaluated at the 0th, 8th, 12th, 16-18th, and 20-24th week of UVR. Skin phenotype was assessed using optical coherence tomography (OCT) and skin image. H&E and Masson's trichrome staining evaluated epidermis and dermis. The structure of lymphatic vessels (LVs), blood vessels, and different types of T cells were evaluated by immunohistochemistry staining. The expression of Piezo1 whose deletion in adult lymphatics led to substantial valve degeneration, VE-cadherin that maintained the permeability of LVs, and YAP1 were evaluated by immunohistochemistry staining as well. Besides, the drainage function of LVs was assessed by Evans Blue assay in vivo. RESULTS:The lymphatic function and immune cell infiltration underwent adaptive changes under continuous UVR. TIMER2.0 analysis indicated that VEGFC genes high expressed in HNSCC. YAP1 gene expression was positive correlated with VEGFC in HNSCC. LV density increased in human cSCC. More LVs in HNSCC were beneficial to prolong the survival time. VEGFC gene overexpression was positive correlated to CD8T cell infiltration. More CD8AT cells and CD8BT cell infiltration in HNSCC extended survival time. When YAP1 gene overexpression and high infiltration of endothelial cells took place simultaneously might prolong the survival time of HNSCC patients. And high infiltration of CD8T cells prolonged the survival time as well. In animal studies, UVR-induced eight weeks (photoaging) and 16-18 weeks (precancerous) were two turning points. The density of LVs in UV-8w was the least. When photoaged skin developed into AK lesions (UV-16-18w), LV slightly exceeded healthy skin and proliferated sharply in cSCC (UV-20-24w). YAP1 expression was almost consistent with LV but rose after the photoaging stage. The drainage of cSCC mice induced by UVR was better than that of photoaged skin and worse than that of health skin. The dynamic alterations of LVs number, Piezo1 expression, and collagen might be reasons for it. The expression of Piezo1 was in the highest point after 8 weeks of UVR, then gradually descended to the platform. The total T cells increased slowly, but the infiltration of CD4T cells increased, and CD8T cells decreased after eight weeks of UVR. The CD8T cells and CD4T cells increased sharply in UV-16-18w and UV-20-24w groups. CONCLUSION:The lymphatic-centered immune microenvironment underwent adaptive changes under continuous UVR via regulating YAP1/VEGFC and Piezo1. During the formation of cSCC, there are two turning points, eight weeks (photoaging) and 16-18 weeks (precancerous). YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes the process of cSCC can be identified in advance and intervene timely.
10.1186/s12967-023-04458-z
Alterations of the pigmentation system in the aging process.
Kang Hee Young,Lee Jin Wook,Papaccio Federica,Bellei Barbara,Picardo Mauro
Pigment cell & melanoma research
Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure. Aging affects nearly every aspect of cutaneous biology, including pigmentation. Clinically, the phenotype of age pigmented skin has a mottled, uneven color, primarily due to age spots, with or without hypopigmentation. Uneven pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment, and turnover. In addition to direct damage to pigment-producing cells, photodamage alters the physiological crosstalk between keratinocytes, fibroblasts, endothelial cells, and melanocytes responsible for natural pigmentation homeostasis. Interestingly, age-independent diffuse expression of senescence-associated markers in the dermal and epidermal compartment is also associated with vitiligo, suggesting that premature senescence plays an important role in the pathology.
10.1111/pcmr.12994
ErZhiFormula prevents UV-induced skin photoaging by Nrf2/HO-1/NQO1 signaling: An in vitro and in vivo studies.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:ErZhiFormula (EZF) is a classical traditional Chinese medicinal formulation. It can be used to treat liver and kidney yin deficiency, dizziness, lumbar debility, insomnia, nocturnal emission, lower extremity weakness, and other aging-related diseases. However, the protective effect of EZF in skin photoaging and its potential mechanism has not been clarified. AIM OF THE STUDY:This study aims to explore the role of EZF in the skin photoaging mechanism induced by UV radiation. MATERIALS AND METHODS:Ultra Performance Liquid Chromatography (UPLC) was used to identify the fingerprint of EZF. The mice were irradiated with UVA and UVB to establish the photoaging model in vivo. Human immortalized keratinocytes (HaCaT) were irradiated with UVB to establish the photoaging model in vitro. The activity of cells was detected by CCK-8 and LDH kits, the level of reactive oxygen species was detected by DCF fluorescent probe, and the apoptosis was detected by PE annexin V and 7-Amino-Actinomycin (7-AAD) staining. Comet assay was used to detect cell DNA damage. The antioxidant enzyme levels in cell and mouse serum were detected by antioxidant kit, and Western blot was used to detect protein expression. RESULTS:We found that EZF contain many active ingredients, including salidroside, specnuezhenide, isoquercitrin, etc. EZF can improve the photoaging of HaCaT cells and mouse skin caused by UV radiation. The results of animal experiments are consistent with those of cell experiments. Combined with Western blot analysis, we found that EZF finally played an anti-skin photoaging role by regulating the Nrf2/HO-1/NQO1 pathway. CONCLUSIONS:EZF can protect skin from UV-induced photoaging by regulating the Nrf2/HO-1/NQO1 signal pathway. EZF may become a traditional Chinese medicine with the potential to prevent skin photoaging.
10.1016/j.jep.2022.115935
Effects of 20-hydroxyecdysone on UVB-induced photoaging in hairless mice.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
We recently reported that exposure of skin to ultraviolet B (UVB) irradiation for 2 weeks induces stress and accelerates skin aging. Interestingly, aldosterone synthase is known to be crucial in generating UVB-induced stress-related responses, suggesting that drugs that regulate its activity can be used as skin antiaging agents. Through extensive drug screening, we have identified 20-hydroxyecdysone (20E), a steroidal prohormone secreted by the prothoracic glands of insects, as a potent inhibitor of UVB-induced aging. Although 20E has been shown to exert antistress and anti-collagenase effects in vitro, its effects in vivo remain unexplored. Furthermore, the pharmacological and physiological effects of 20E on UVB-mediated photoaging are poorly understood. Therefore, in this study, we investigated the effects of 20E on aldosterone synthase and UVB-induced photoaging and skin lesions in hairless mice, focusing on the stress-related hypothalamic-pituitary-adrenal axis. We confirmed that 20E inhibited aldosterone synthase and reduced corticosterone levels. When applied to a UV-induced skin aging animal model, it ameliorated UV-induced stress and protected against the decrease in collagen levels. Importantly, when the aldosterone synthase inhibitor osilodrostat, an FDA-approved drug, was applied to the UV-induced skin aging model, the stress-reducing and antiaging effects of 20E were not observed. Thus, we conclude that 20E inhibits UVB-induced skin aging by blocking aldosterone synthase and is a potential candidate to prevent skin aging.
10.1016/j.biopha.2023.114899
Ganoderma lucidum polysaccharide inhibits UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways.
Hu Shuanghai,Huang Jinhua,Pei Shiyao,Ouyang Yujie,Ding Yufang,Jiang Ling,Lu Jianyun,Kang Liyang,Huang Lihua,Xiang Hong,Xiao Rong,Zeng Qinghai,Chen Jing
Journal of cellular physiology
Ultraviolet (UV)-induced pigmentation is very common in clinical practice, but the current treatments are rarely effective, accompanied by some side effects. Ganoderma lucidum polysaccharide (GLP) is a natural antioxidant with no toxic side effects, which can antagonize UVB-induced fibroblast photo aging. The study aims to explore the role of GLP in inhibiting UVB-induced melanogenesis and its possible mechanism. The expression of melanogenesis genes such as microphthalmia-associated transcription factor (MITF), tyrosine (TYR), tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2), ras-related protein Rab-27A (Rab27A), and Myosin shows an upward trend after exposure of B16F10 and PIG1 cells to UVB irradiation, but GLP can downregulate the expression of genes related to UVB-induced melanogenesis. GLP can inhibit UVB-activated protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) signaling pathways. Besides, GLP protects mitochondria from UVB damage and inhibits reactive oxygen species (ROS) production. Also, UVB-induced cyclic adenosine monophosphate (cAMP) can be inhibited. It has been found in the experiments of UVB-induced skin pigmentation in zebrafish that GLP is capable of inhibiting UVB-induced skin pigmentation. Meanwhile, it can greatly relieve erythema reaction in guinea pig skin caused by high-dosage UVB irradiation. In conclusion, this study shows that GLP can inhibit UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways and is a potential natural safe whitening sunscreen additive.
10.1002/jcp.27492
Caffeine Protects Skin from Oxidative Stress-Induced Senescence through the Activation of Autophagy.
Theranostics
Skin cells are vulnerable to oxidative stress-induced senescence, which may lead to abnormal aging or aging-related disorders. Therefore, strategies that can ameliorate oxidative stress-induced senescence are expected to protect skin from damage, holding the promise of treating skin diseases in the clinic. This study aims to investigate whether caffeine, a well-known purine alkaloid, is able to prevent skin from oxidative stress-induced senescence, and to explore the underlying molecular mechanisms. : A free radical inducer 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was used to induce oxidative stress and cellular senescence in both transformed skin cells and in normal human epidermal keratinocytes (NHEKs). Ultraviolet (UV) irradiation was established as the oxidative stress model in mouse skin tissues. Cellular senescence was determined by SA β-galactosidase staining, immunofluorescence and western blotting. Activation of autophagy was confirmed by western blotting, immunofluorescence, and transmission electron microscopy. Reactive oxygen species (ROS) detection by commercial kits, gene knockdown by RNA interference (RNAi) and receptor activation/inactivation by agonist/antagonist treatment were applied in mechanistic experiments. : We report that AAPH induced senescence in both transformed skin cells and in NHEKs. Similarly, UV irradiation induced senescence in mouse skin tissues. Remarkably, low dose of caffeine (<10 μM) suppressed cellular senescence and skin damage induced by AAPH or UV. Mechanistically, caffeine facilitated the elimination of ROS by activating autophagy. Using a combination of RNAi and chemical treatment, we demonstrate that caffeine activates autophagy through a series of sequential events, starting from the inhibition of its primary cellular target adenosine A2a receptor (A2AR) to an increase in the protein level of Sirtuin 3 (SIRT3) and to the activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Oral administration of caffeine increased the protein level of SIRT3, induced autophagy, and reduced senescence and tissue damage in UV-irradiated mouse skin. On the other hand, co-administration with autophagy inhibitors attenuated the protective effect of caffeine on UV-induced skin damage in mice. : The results reveal that caffeine protects skin from oxidative stress-induced senescence through activating the A2AR/SIRT3/AMPK-mediated autophagy. Our study not only demonstrated the beneficial effect of caffeine using both and models, but also systematically investigated the underlying molecular mechanisms. These discoveries implicate the potential of caffeine in the protection of skin disease.
10.7150/thno.28778
UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner.
JCI insight
It is currently thought that UVB radiation drives photoaging of the skin primarily by generating ROS. In this model, ROS purportedly activates activator protein-1 to upregulate MMPs 1, 3, and 9, which then degrade collagen and other extracellular matrix components to produce wrinkles. However, these MMPs are expressed at relatively low levels and correlate poorly with wrinkles, suggesting that another mechanism distinct from ROS and MMP1/3/9 may be more directly associated with photoaging. Here we show that MMP2, which degrades type IV collagen, is abundantly expressed in human skin, increases with age in sun-exposed skin, and correlates robustly with aryl hydrocarbon receptor (AhR), a transcription factor directly activated by UV-generated photometabolites. Through mechanistic studies with HaCaT human immortalized keratinocytes, we found that AhR, specificity protein 1 (SP1), and other pathways associated with DNA damage are required for the induction of both MMP2 and MMP11 (another MMP implicated in photoaging), but not MMP1/3. Last, we found that topical treatment with AhR antagonists vitamin B12 and folic acid ameliorated UVB-induced wrinkle formation in mice while dampening MMP2 expression in the skin. These results directly implicate DNA damage in photoaging and reveal AhR as a potential target for preventing wrinkles.
10.1172/jci.insight.156344