Skin Pharmacology and Physiology最新文献

{"title":"Thiophene-Benzimidazole Conjugates Attenuate IL-33-induced Inflammation in Human Mast Cell Line and in ex vivo Human Skin Organ Cultures.","authors":"Raanan Gvirtz, Shirin Kahremany, Lena Trifonov, Sagiv Weintraub, Edward E Korshin, Eldad Silberstein, Nataliia Shtil, Mykhailo Kompanets, Tomer Ayzenberg, Navit Ogen-Shtern, Guy Cohen, Arie Gruzman","doi":"10.1159/spp/aetag017","DOIUrl":"https://doi.org/10.1159/spp/aetag017","url":null,"abstract":"<p><strong>Introduction: </strong>Aberrant Interleukin-33 (IL-33) activation is associated with numerous dermatological inflammatory and autoimmune diseases, such as atopic dermatitis, lupus, vitiligo and psoriasis. Thus, the inhibition of this pathway may provide therapeutic options in multiple pathologies. We hypothesized that targeting the IL-33 critical site of interactions with its membranal receptor, Suppression of Tumorigenicity 2 (ST2), will generate highly selective inhibitors capable of alleviating the detrimental effects of IL-33 activation.</p><p><strong>Methods: </strong>In silico-based methods for the identification of possible inhibitors of IL-33/ST2 interaction were used. Employing two structure-based pharmacophore models designed by LigandScout, a virtual screening of commercially available compounds and in house library revealed 13 compounds that may reduce level of IL-33/ST2 interaction. To verify their capacity to attenuate IL-33-induced inflammation, the compounds were tested in HMC-1.1 mast cell line and human skin slices.</p><p><strong>Results: </strong>Two lead compounds, both thiophene-benzimidazole conjugates methyl-1-(pentan-3-yl)-2-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole-5-carboxylate (LT-105) and methyl (S)-5-methyl-3-{(1-(pentan-3-yl)-2-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole-5-carboxamido)}hexanoate (LT-108), were able to attenuate IL-33-induced IL-6 and IL 8 hypersecretion in pharmacological relevant concentrations. This effect correlated with reduced IL-6 and IL-8 mRNA levels, determined by RT-PCR. In addition, LT-105 and LT-108 reduced the phosphorylation of IL-33 downstream effectors; p-IRAK1 and p-P38. Further docking studies revealed possible molecular interactions of the compounds with key sites of IL-33 that are responsible for the binding with ST2. To validate the findings, the compounds were also tested in the ex vivo human skin organ culture. Both compounds LT-105 and LT-108 reduced inflammation when applied topically to the human skin samples stimulated by IL-33 in pharmacological concentrations.</p><p><strong>Conclusions: </strong>Our results indicate that thiophene-benzimidazole conjugates LT-105 and LT-108 can reduce IL-33 mediated inflammation both in vitro and ex vivo. Nevertheless, additional in vivo and clinical studies are required to further evaluate the ability of these compounds to treat autoimmune/inflammatory cutaneous disorders mediated by IL-33.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-Stage Derisking of a Topical JAK Inhibitor Candidate in Healthy Human Skin Explants: Dermal Stability and Pharmacokinetics.","authors":"Thomas Birngruber, Katrin Tiffner, Frank Sinner, Simon Schwingenschuh, Sylvia Furst, Stephan Bielfeldt, Brigitte Stephan","doi":"10.1159/spp/aetag018","DOIUrl":"https://doi.org/10.1159/spp/aetag018","url":null,"abstract":"<p><strong>Purpose: </strong>Topical JAK inhibitors (JAKi) offer promising treatment for inflammatory skin disorders while minimizing systemic side effects. Understanding their pharmacokinetic and pharmacodynamic properties in skin is essential for their development. This pharmacokinetic study evaluated dermal penetration, metabolism, and stability of a novel, topical JAKi candidate and its inactive metabolite using dermal open flow microperfusion (dOFM) as a translational technology bridging ex vivo to in vivo findings.</p><p><strong>Patients and methods: </strong>Skin penetration of parent compound (JAKi-o) was investigated ex vivo in human skin explants from three donors by dOFM sampling. Different test formulations (0.75%, 1.5%) and different dosing were compared with approved ruxolitinib 1.5% cream as reference. Stability and metabolic conversion into the inactive metabolite (JAKi-mb) were tested in extracted interstitial fluid and ex vivo after intradermal dOFM application.</p><p><strong>Results: </strong>Topical JAKi-o formulations (0.75%; 1.5%) produced dermal concentrations below the quantification limit (5 nM) at all timepoints. Reference ruxolitinib showed continuous concentration increases, reaching levels 63 times higher than the maximum JAKi-o concentrations. Pharmacokinetic profiles were consistent between explants and occlusion did not significantly affect dermal concentrations. Metabolic conversion in pure ISF was minimal, with only 14.4% of JAKi-o metabolized to JAKi-mb after 120 minutes. Intradermal application via dOFM confirmed intradermal metabolism, with a ratio of 1.6 (JAKi-o to JAKi-mb) during intradermal JAKi-o application which reversed to a ratio of 0.8 (JAKi-o to JAKi-mb) when only residual JAKi-o from the dermal tissue was available for metabolism.</p><p><strong>Conclusion: </strong>dOFM effectively detected dermal penetration and metabolism of small molecules in human skin ex-vivo, enabling prediction of human metabolization behaviour. This time-saving preclinical method supports early-phase drug development by determining whether compounds achieve sufficient skin concentrations without systemic availability, allowing early candidate selection and reducing development risks for topical therapies targeting epidermis and dermis.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a Ceramide NP-Containing Moisturizer on Skin Barrier Function in Adults with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study.","authors":"Chaoying Gu, Jiayi Ying, Huibin Yin, Chunyun Huang, Leihong Xiang","doi":"10.1159/spp/aetag011","DOIUrl":"https://doi.org/10.1159/spp/aetag011","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effects of a ceramide NP-containing soothing and moisturizing emollient cream on skin-barrier function in adult patients with atopic dermatitis (AD).</p><p><strong>Methods: </strong>In this single-center, randomized, double-blind, placebo-controlled parallel trial, 60 adults with moderate atopic dermatitis were randomly assigned (1:1) to receive standard therapy with either the soothing and moisturizing emollient cream or placebo. Skin barrier parameters and clinical outcomes were assessed on Days 21 and 42.</p><p><strong>Results: </strong>Both groups demonstrated overall improvements in skin barrier parameters, including stratum corneum hydration, TEWL, and casual sebum levels, with generally more favorable numerical trends observed in the intervention group. However, between-group differences in changes from baseline did not reach statistical significance, and no significant between-group differences were observed in skin surface pH. All clinical outcomes, including EASI, SCORAD, DLQI, and pruritus and insomnia VAS scores, improved significantly from baseline in both groups (P < 0.05), with numerically greater improvements generally observed in the intervention group and more pronounced improvements at Day 42 than at Day 21.</p><p><strong>Conclusion: </strong>This study evaluated the incremental value of the emollient under real-world clinical conditions. the soothing and moisturizing emollient cream showed favorable trends in improving skin barrier parameters and clinical symptoms in adults with AD when used as an adjunct to standard therapy. Larger, rigorously designed studies are warranted to confirm its efficacy and long-term clinical value.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of SIRT6 Using a Hydrolyzed Yeast Protein Extract to Enhance Skin Longevity by Targeting Multiple Hallmarks of Aging.","authors":"Kelly Dong, Antonella Rella, Earl C Goyarts, Jacqueline Trivero, Nadine Pernodet, Rishabh Kala","doi":"10.1159/spp/aetag015","DOIUrl":"https://doi.org/10.1159/spp/aetag015","url":null,"abstract":"<p><strong>Introduction: </strong>Photoaging and chronological age-related changes in cellular functioning such as telomere attrition can lead to accumulation of senescent skin cells, a key driver of age-related decline in skin integrity and function. Activation of sirtuins (SIRTs), master epigenetic regulators of cellular functioning and homeostasis in skin, may be a promising approach to protect skin cells from the effects of photoaging and cellular hallmarks of skin aging.</p><p><strong>Methods: </strong>In a series of in vitro studies, we evaluated the potential for a SIRT6 activator, a proprietary Hydrolyzed Yeast Protein Extract (HYPE), to modulate the response of normal human epidermal keratinocytes (NHEK) to UVB radiation, the rate of telomere attrition in dermal fibroblasts, and melanin content in melanocytes in a 3D skin model.</p><p><strong>Results: </strong>Treatment with HYPE increased SIRT6 protein expression in NHEK and SIRT6 gene expression in dermal fibroblasts, attenuated NF-κB-mediated inflammation in keratinocytes following UVB exposure, protected keratinocytes from DNA damage following UVB irradiation, decreased the rate of telomere attrition in aged dermal fibroblasts, and reduced melanin content in melanocytes in a 3D skin model.</p><p><strong>Conclusion: </strong>The potential for the SIRT6 activator HYPE to address multiple hallmarks of skin aging, and its activity in all 3 types of skin cells, makes it a potential agent to incorporate into skincare formulations designed to reverse visible aging.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimelanogenic Effects of Lactobacillus helveticus-Fermented Whey in a-MSH-Stimulated Melanoma Cells and UV-Irradiated Mice.","authors":"Yui Shinozaki, Nobutomo Ikarashi, Yui Nishinaka, Rinka Saito, Keito Tabata, Koki Yokoyama, Suzu Saito, Risako Kon, Hiroyasu Sakai, Akira Sugiyama, Sachiyo Nomura, Tomoo Hosoe","doi":"10.1159/spp/aetag016","DOIUrl":"https://doi.org/10.1159/spp/aetag016","url":null,"abstract":"<p><strong>Introduction: </strong>Lactic acid bacteria have various beneficial effects on humans and are widely used in the production of fermented foods. The whey generated by lactic acid bacteria during milk fermentation has been reported to increase the expression of skin moisturizing factors. This study aimed to elucidate the effects of whey on ultraviolet (UV)-induced skin pigmentation.</p><p><strong>Methods: </strong>The effects of α-melanocyte-stimulating hormone (α-MSH) alone or in combination with whey on melanin production were evaluated in mouse melanoma B16 cells. In addition, whey was topically applied to UV-irradiated HRM-2 mice, and the skin melanin content and the expression levels of melanogenesis-related enzymes (tyrosinase [TYR], tyrosinase-related protein 1 [TYRP1], and dopachrome tautomerase [DCT]) and microphthalmia-associated transcription factor (Mitf) were analyzed.</p><p><strong>Results: </strong>Whey significantly suppressed the α-MSH-induced melanin production increase in B16 cells in a concentration-dependent manner. UV irradiation significantly increased the skin melanin content in HRM-2 mice compared to that in the control group, which was markedly reduced by whey treatment. Furthermore, whey significantly inhibited the UV-induced upregulation of melanogenesis-related enzymes. Similarly, whey suppressed the expression of Mitf, a key transcription factor that regulates melanogenic enzyme expression.</p><p><strong>Conclusion: </strong>Topical application of whey suppressed UV-induced skin pigmentation by inhibiting Mitf expression, leading to reduced expression of downstream melanogenic enzymes, TYR, TYRP1, and DCT. These findings suggest that whey is a promising cosmetic ingredient for preventing or attenuating the progression of skin pigmentation.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of extreme environmental conditions on the skin barrier: a pilot study from the \"Under The Pole\" project with spectral and biometric measurements.","authors":"Aline Rigal-Dachaud, Rime Michael-Jubeli, Alex Nkengne, Katell Vie, Arlette Baillet-Guffroy, Armelle Bigouret, Ali Tfayli","doi":"10.1159/spp/aetag004","DOIUrl":"https://doi.org/10.1159/spp/aetag004","url":null,"abstract":"<p><strong>Introduction: </strong>Under The Pole is an ambitious underwater exploration program in extreme environments, particularly in deep and polar regions. Diving in the cold and saline waters of the Arctic exposes the skin to intense thermal and osmotic stress, potentially altering its barrier function. This study aimed to evaluate both the acute and long-term effects of repeated cold-water diving on skin hydration and barrier integrity during a two-month Arctic expedition.</p><p><strong>Methods: </strong>Seven healthy Caucasian male participants without facial skin lesions were monitored throughout the expedition. Skin appearance, hydration and transepidermal water loss (TEWL) were measured. Stratum corneum (SC) samples were collected by tape stripping and analyzed using Raman spectroscopy and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy to assess molecular changes in lipids and proteins.</p><p><strong>Results: </strong>The findings reveal a dynamic, multiphasic adaptation process of the skin barrier under extreme polar conditions: (i) Immediate phase (hours): Acute hydration increase and transient barrier disruption due to immersion and temperature shock. (ii) Short-term phase (days): Adaptive homeostatic response, characterized by decreased water loss and lipid disorganization and protein structural rearrangement within the SC. (iii) Long-term phase (weeks): Gradual barrier fatigue with partial recovery of lipid order and protein structure, but persistent microstructural alterations evidenced by reduced hydration and elevated TEWL.</p><p><strong>Conclusion: </strong>This study provides in situ evidence of dynamic skin adaptation to extreme Arctic conditions. Initial barrier disruption was followed by molecular reorganization and partial recovery, yet prolonged exposure led to cumulative dehydration and barrier fatigue. These insights improve understanding of cutaneous resilience and support the design of protective skincare strategies for extreme environments.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Topical Emollients on Skin Biophysical Properties and Inflammatory Markers in Stasis Eczema.","authors":"Jo Aan Goon, Adawiyah Jamil, Imran Al-Jameel, Siti Liyana Saud Gany, Wei Ney Yap, Hsieu Yen Loong, Yee Wei Ung","doi":"10.1159/spp/aetag006","DOIUrl":"10.1159/spp/aetag006","url":null,"abstract":"<p><strong>Introduction: </strong>Stasis eczema is a chronic inflammatory skin condition commonly associated with chronic venous insufficiency and represents a significant clinical burden. Emollients are widely used to improve skin hydration and barrier function; however, their effects on inflammation and skin remodeling in stasis eczema remain unclear. This study aimed to evaluate the impact of a topical emollient on skin barrier integrity and systemic inflammatory markers in affected patients.</p><p><strong>Methods: </strong>Fifty patients with stasis eczema were randomized to receive either a topical emollient or placebo for 6 weeks. Skin parameters, including melanin content, hydration, and transepidermal water loss, were assessed using Tewameter. Plasma levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), anti-inflammatory cytokine IL-10, and matrix metalloproteinases (MMPs: MMP-1, MMP-2, MMP-3, and MMP-9) were measured using enzyme-linked immunosorbent assay at baseline and after treatment.</p><p><strong>Results: </strong>Baseline clinical assessment demonstrated a high prevalence of comorbidities, particularly hypertension, chronic venous insufficiency, diabetes mellitus, and dyslipidemia. No statistically significant changes were observed in skin barrier parameters or circulating cytokine levels following 6 weeks of treatment. MMP-1 and MMP-2 concentrations remained stable in both groups. However, posttreatment MMP-3 levels were significantly higher in the emollient group than in the placebo group, while MMP-9 demonstrated a significant within-group change in the placebo group only.</p><p><strong>Conclusion: </strong>Short-term use of a topical emollient may help maintain skin barrier function and systemic inflammatory status but does not appear to produce clinically meaningful improvements in most skin barriers or inflammatory parameters, despite isolated significant changes observed in specific MMP biomarkers in patients with chronic stasis eczema. These findings highlight the complexity of disease management in this population and suggest that longer treatment durations, larger sample sizes, consideration and statistical adjustment for baseline comorbidities are warranted in future studies.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Mucopolysaccharide Polysulfate on Sweating Function and Skin Dryness in a Mouse Model of Streptozotocin-Induced Diabetes.","authors":"Wataru Sugimoto, Hironobu Ishimaru, Sanae Hirota, Ryo Tadakuma, Ryo Aikawa, Rina Furumoto, Takaaki Doi, Yuhki Ueda","doi":"10.1159/spp/aetag005","DOIUrl":"10.1159/spp/aetag005","url":null,"abstract":"<p><strong>Introduction: </strong>Asteatosis is characterized by reduced water content in the stratum corneum. Patients with diabetes have been reported to experience reduced sweating, potentially leading to asteatosis. A common treatment approach for asteatosis is the use of moisturizers, such as mucopolysaccharide polysulfate (MPS) cream. However, the therapeutic mechanism of MPS in diabetes-induced asteatosis remains unknown. In this study, we investigated the role of sweating in the pathophysiology of asteatosis in diabetes and to confirm the therapeutic effect of MPS cream using a streptozotocin (STZ)-induced diabetic mouse model (STZ-DM mice).</p><p><strong>Methods: </strong>STZ-DM mice were generated by administering STZ to C57BL/6JJcl mice. Approximately 2 weeks after STZ administration, sweating function and skin surface hydration in the footpads, where sweat glands are located, were evaluated, with or without topical occlusive application of moisturizers including MPS cream for more than 10 days.</p><p><strong>Results: </strong>After STZ treatment, sweating function in STZ-DM mice gradually decreased from week 3 to 9. Furthermore, skin surface hydration and sweating function decreased over time. Topical application of MPS cream alleviated diminished sweating and skin surface hydration in STZ-DM mice. Moreover, pilocarpine-induced sweating response was attenuated in STZ-DM mice, indicating that impairment of sweating function in these mice involves neuropathic dysfunction. Topical application of MPS cream improved the pilocarpine-induced sweating response.</p><p><strong>Conclusion: </strong>The effects of MPS on the increasing water content of SC in STZ-DM mice may be partly mediated by sweating. This is the first study to demonstrate that the ameliorative effect of MPS on diabetic dry skin is mediated by enhanced sweating via neuropathy inhibition.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Endoplasmic Reticulum Stress in Extrinsic Skin Aging and Protective Strategies of Natural Plant Products.","authors":"Ying Liu, Huiyuan Huang, Xiaotian Ji, Lei Li, Liping Ma, Mingfang Zhu","doi":"10.1159/spp/aetag013","DOIUrl":"https://doi.org/10.1159/spp/aetag013","url":null,"abstract":"<p><strong>Background: </strong>The complicated process of extrinsic skin aging is brought on by long-term exposure to ultraviolet (UV) radiation, air pollution, and other environmental stressors. Its primary manifestations include deep wrinkles, skin laxity, abnormal pigmentation, epidermal barrier dysfunction, chronic inflammation, and telangiectasia. According to recent research, endoplasmic reticulum stress (ERS) is an important stress mechanism involved in extrinsic skin aging. Through the production of reactive oxygen species (ROS), disruption of Ca2+ homeostasis, and defects in protein folding, extrinsic environmental stressors can activate ERS and cause the unfolded protein response (UPR).</p><p><strong>Summary: </strong>ERS-induced UPR activation initially functions as a protective mechanism that restores endoplasmic reticulum (ER) homeostasis by enhancing protein-folding capacity, promoting ER-associated degradation (ERAD), and attenuating global protein translation. However, under persistent or severe ER stress, sustained UPR signaling may shift from a homeostatic response toward a detrimental response and contribute to the development of characteristic cutaneous phenotypes of extrinsic skin aging, including wrinkles, hyperpigmentation, epidermal barrier dysfunction, chronic inflammation, and telangiectasia, through increased oxidative stress, amplification of inflammatory responses, and induction of cellular senescence and apoptosis. An increasing amount of evidence suggests that natural plant products can prevent or alleviate extrinsic skin aging by regulating ERS and related processes, including apoptosis, autophagy, and oxidative stress.</p><p><strong>Key messages: </strong>This review summarizes the major molecular mechanisms of ERS in extrinsic skin aging and its associations with various aging phenotypes, outlining potential intervention strategies using natural plant products.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vanillyl butyl ether patch application enhances thermosensory perception and alters microcirculatory dynamics in the forearm: a randomized double-blind crossover trial.","authors":"Eisuke Morimoto, Shoya Mori, Masahiro Matsui, Akane Fujioka, Osamu Takeda, Tomomi Fujimoto, Keisei Kosaki","doi":"10.1159/spp/aetag014","DOIUrl":"https://doi.org/10.1159/spp/aetag014","url":null,"abstract":"<p><strong>Introduction: </strong>Transient receptor potential vanilloid 1 (TRPV1) channels contribute to thermosensory perception and microvascular regulation; however, the physiological effects of the non-pungent TRPV1 agonist vanillyl butyl ether (VBE) in humans remain unclear.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled crossover trial investigated the acute effects of a VBE patch application on cutaneous circulation and thermal perception in 13 healthy adults. Participants received a 30-min application of either a VBE patch or a visually identical placebo patch on the forearm while cutaneous blood flow, skin temperature, and muscle oxygenation were continuously monitored, and subjective thermal sensation and comfort were assessed every 2 min.</p><p><strong>Results: </strong>The VBE patch condition showed an increase in cutaneous blood flow without altering skin temperature or muscle oxygenation, indicating a localized superficial microvascular effect. VBE also induced warmth sensations and greater thermal discomfort than placebo, with ratings corresponding to a level between \"slightly uncomfortable\" and \"uncomfortable.\"</p><p><strong>Conclusion: </strong>These findings suggest that topical VBE may increase cutaneous blood flow and alter thermosensory responses without producing measurable changes in skin temperature or muscle oxygen saturation.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":" ","pages":"1"},"PeriodicalIF":4.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}