Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel
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 <i>Cistanche deserticola</i> commonly used for therapies and treatments for anti-aging and irradiation-related skin di...
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2025-05-01
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| author | Shilun Mo Xinying Yue Yaxuan Qu Guoji Zhang Liqin Wang Xiaoying Sun |
| author_facet | Shilun Mo Xinying Yue Yaxuan Qu Guoji Zhang Liqin Wang Xiaoying Sun |
| author_sort | Shilun Mo |
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| description | 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 <i>Cistanche deserticola</i> 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 Ca<sup>2+</sup>-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 <i>Trpv3</i> 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 IC<sub>50</sub> value of 21.94 ± 1.28 μM. 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. |
| format | Article |
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| language | English |
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| spelling | doaj-art-b41242d03d544b8f96bf1d552b3f05112025-08-20T02:24:55ZengMDPI AGMolecules1420-30492025-05-01309202610.3390/molecules30092026Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 ChannelShilun Mo0Xinying Yue1Yaxuan Qu2Guoji Zhang3Liqin Wang4Xiaoying Sun5Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaDepartment of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaDepartment of Pharmacology, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaDepartment of Pharmacology, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaDepartment of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaDepartment of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao Medical College of Qingdao University, 1 Ningde Road, Qingdao 266073, ChinaExcessive 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 <i>Cistanche deserticola</i> 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 Ca<sup>2+</sup>-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 <i>Trpv3</i> 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 IC<sub>50</sub> value of 21.94 ± 1.28 μM. 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.https://www.mdpi.com/1420-3049/30/9/2026acute skin injuryechinacosideTRPV3UVB |
| spellingShingle | Shilun Mo Xinying Yue Yaxuan Qu Guoji Zhang Liqin Wang Xiaoying Sun Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel Molecules acute skin injury echinacoside TRPV3 UVB |
| title | Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel |
| title_full | Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel |
| title_fullStr | Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel |
| title_full_unstemmed | Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel |
| title_short | Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel |
| title_sort | echinacoside ameliorates uvb induced skin damage through selective inhibition of the cutaneous trpv3 channel |
| topic | acute skin injury echinacoside TRPV3 UVB |
| url | https://www.mdpi.com/1420-3049/30/9/2026 |
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