{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:49:47Z","timestamp":1781700587376,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH081"],"award-info":[{"award-number":["ZR2023MH081"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["81903734"],"award-info":[{"award-number":["81903734"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZR2023MH081"],"award-info":[{"award-number":["ZR2023MH081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903734"],"award-info":[{"award-number":["81903734"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Excessive exposure to ultraviolet B (UVB) radiation can lead to skin damage, such as erythema and swelling. Echinacoside is a key effective ingredient of medicinal plant Cistanche deserticola commonly used for therapies and treatments for anti-aging and irradiation-related skin diseases. However, the molecular mechanism underlying the action of echinacoside remains unclear. Here, we report that echinacoside ameliorates UVB-induced skin damage by directly acting on the Ca2+-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) channel. Topical application of echinacoside efficaciously suppresses skin lesions induced by UVB radiation in wild-type mice but has no additional benefit in Trpv3 knockout mice. In whole-cell patch clamp recordings, echinacoside selectively inhibits TRPV3 channel currents induced by 2-aminoethoxydiphenyl borate in a concentration-dependent manner with an IC50 value of 21.94 \u00b1 1.28 \u03bcM. The single-channel patch clamp results show that echinacoside significantly reduces the open probability and open frequency without significantly altering TRPV3 channel unitary conductance. Molecular docking and site-specific mutagenesis indicate that residue T636 on the p-loop and residue T665 on the S6 segment of TRPV3 are critical for echinacoside binding to TRPV3. Taken together, our findings provide a molecular basis for further studies as use of natural echinacoside in irradiation-related skin care therapy, thus establishing a significant role of the TRPV3 channel in acute skin injury.<\/jats:p>","DOI":"10.3390\/molecules30092026","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:44:58Z","timestamp":1746171898000},"page":"2026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel"],"prefix":"10.3390","volume":"30","author":[{"given":"Shilun","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-973X","authenticated-orcid":false,"given":"Xiaoying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, China"},{"name":"Institute of Innovative Drugs, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/j.1529-8019.2012.01460.x","article-title":"Skin biology","volume":"24","author":"Hwa","year":"2011","journal-title":"Dermatol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1111\/jocd.16155","article-title":"Skin homeostasis: Mechanism and influencing factors","volume":"23","author":"Jiao","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1111\/jdv.17242","article-title":"Photoprotection according to skin phototype and dermatoses: Practical recommendations from an expert panel","volume":"35","author":"Passeron","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jdv.13603","article-title":"Skin cancer risk in outdoor workers: A European multicenter case\u2013control study","volume":"30","author":"Trakatelli","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.arr.2015.01.001","article-title":"Oxidation events and skin aging","volume":"21","author":"Kammeyer","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.taap.2003.08.019","article-title":"Toxic effects of ultraviolet radiation on the skin","volume":"195","author":"Matsumura","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jid.2017.09.002","article-title":"UV-B-Induced Erythema in Human Skin: The Circadian Clock Is Ticking","volume":"138","author":"Sarkar","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.tiv.2018.08.013","article-title":"Human skin explants an in vitro approach for assessing UVB induced damage","volume":"53","author":"Khalil","year":"2018","journal-title":"Toxicol. In Vitro"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10522-017-9715-7","article-title":"Plant extracts and natural compounds used against UVB-induced photoaging","volume":"18","author":"Cavinato","year":"2017","journal-title":"Biogerontology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000538832","article-title":"Preventive and Therapeutic Benefits of Natural Ingredients in Photo-Induced Epidermal Dysfunction","volume":"37","author":"Lei","year":"2024","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Milutinov, J., Pavlovi\u0107, N., \u0106irin, D., Atanackovi\u0107 Krstono\u0161i\u0107, M., and Krstono\u0161i\u0107, V. (2024). The Potential of Natural Compounds in UV Protection Products. Molecules, 29.","DOI":"10.3390\/molecules29225409"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/med.21768","article-title":"Cistanches Herba, from an endangered species to a big brand of Chinese medicine","volume":"41","author":"Song","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, Z., Lin, H., Gu, L., Gao, J., and Tzeng, C.-M. (2016). Herba Cistanche (Rou Cong-Rong): One of the Best Pharmaceutical Gifts of Traditional Chinese Medicine. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00041"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"740","DOI":"10.14336\/AD.2017.0720","article-title":"Herba Cistanches: Anti-aging","volume":"8","author":"Jin","year":"2017","journal-title":"Aging Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhou, S., Feng, D., Zhou, Y., Duan, H., Jiang, Y., and Yan, W. (2023). Analysis of the active ingredients and health applications of cistanche. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1101182"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jpba.2018.11.053","article-title":"Exploring the halophyte Cistanche phelypaea (L.) Cout as a source of health promoting products: In vitro antioxidant and enzyme inhibitory properties, metabolomic profile and computational studies","volume":"165","author":"Trampetti","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.apsb.2017.07.003","article-title":"Application of 1 H NMR-based metabolomics for discrimination of different parts and development of a new processing workflow for Cistanche deserticola","volume":"7","author":"Zou","year":"2017","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6851464","DOI":"10.1155\/2017\/6851464","article-title":"Echinacoside Alleviates UVB Irradiation-Mediated Skin Damage via Inhibition of Oxidative Stress, DNA Damage, and Apoptosis","volume":"2017","author":"Zhang","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wen, S.Y., Ng, S.C., Noriega, L., Chen, T.J., Chen, C.J., Lee, S.D., Huang, C.Y., and Kuo, W.W. (2025). Echinacoside promotes collagen synthesis and survival via activation of IGF-1 signaling to alleviate UVB-induced dermal fibroblast photoaging. Biofactors, 51.","DOI":"10.1002\/biof.2152"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kalinovskii, A.P., Utkina, L.L., Korolkova, Y.V., and Andreev, Y.A. (2023). TRPV3 Ion Channel: From Gene to Pharmacology. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108601"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lei, J., and Tominaga, M. (2024). Unlocking the therapeutic potential of TRPV3: Insights into thermosensation, channel modulation, and skin homeostasis involving TRPV3. Bioessays, 46.","DOI":"10.1002\/bies.202400047"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Su, W., Qiao, X., Wang, W., He, S., Liang, K., and Hong, X. (2023). TRPV3: Structure, Diseases and Modulators. Molecules, 28.","DOI":"10.3390\/molecules28020774"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nature00882","article-title":"TRPV3 is a calcium-permeable temperature-sensitive cation channel","volume":"418","author":"Xu","year":"2002","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1365-2133.2012.11115.x","article-title":"Recurrent heterozygous missense mutation, p.Gly573Ser, in the TRPV3 gene in an Indian boy with sporadic Olmsted syndrome","volume":"167","author":"Sethuraman","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1016\/j.jid.2020.02.028","article-title":"Enhanced Thermal Sensitivity of TRPV3 in Keratinocytes Underlies Heat-Induced Pruritogen Release and Pruritus in Atopic Dermatitis","volume":"140","author":"Seo","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Um, J.Y., Kim, H.B., Kim, J.C., Park, J.S., Lee, S.Y., Chung, B.Y., Park, C.W., and Kim, H.O. (2022). TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314962"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"adv4463","DOI":"10.2340\/actadv.v103.4463","article-title":"Neuroimmune Mediators of Pruritus in Hispanic Scalp Psoriatic Itch","volume":"103","author":"Nattkemper","year":"2023","journal-title":"Acta Derm. Venereol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e23309","DOI":"10.1096\/fj.202301591RR","article-title":"Inhibition of cutaneous heat-sensitive Ca2+-permeable transient receptor potential vanilloid 3 channels alleviates UVB-induced skin lesions in mice","volume":"37","author":"Qu","year":"2023","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1124\/jpet.118.254045","article-title":"Pharmacological Inhibition of the Temperature-Sensitive and Ca2+-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel by Natural Forsythoside B Attenuates Pruritus and Cytotoxicity of Keratinocytes","volume":"368","author":"Zhang","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jdermsci.2020.01.004","article-title":"Anti-pruritic and anti-inflammatory effects of natural verbascoside through selective inhibition of temperature-sensitive Ca2+-permeable TRPV3 channel","volume":"97","author":"Sun","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118557","DOI":"10.1016\/j.lfs.2020.118557","article-title":"Neuronal and non-neuronal transient receptor potential ankyrin 1 mediates UVB radiation-induced skin inflammation in mice","volume":"262","author":"Camponogara","year":"2020","journal-title":"Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/exd.13912","article-title":"Baicalein inhibits matrix metalloproteinase 1 expression via activation ofTRPV1-Ca-ERKpathway in ultraviolet B\u2013irradiated human dermal fibroblasts","volume":"28","author":"Huang","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E3225","DOI":"10.1073\/pnas.1312933110","article-title":"UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling","volume":"110","author":"Moore","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1111\/bph.15913","article-title":"Scutellarein attenuates atopic dermatitis by selectively inhibiting transient receptor potential vanilloid 3 channels","volume":"179","author":"Wang","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.apsb.2021.08.002","article-title":"Inhibition of temperature-sensitive TRPV3 channel by two natural isochlorogenic acid isomers for alleviation of dermatitis and chronic pruritus","volume":"12","author":"Qi","year":"2022","journal-title":"Acta Pharm. Sin. B"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/9\/2026\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:26:14Z","timestamp":1760030774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/9\/2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["molecules30092026"],"URL":"https:\/\/doi.org\/10.3390\/molecules30092026","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]}}}