Department of Physiology, Dongguk University College of Medicine, Gyeongju 38066, Republic of Korea.
Channelopathy Research Center (CRC), Dongguk University College of Medicine, Goyang 10326, Republic of Korea.
Int J Mol Sci. 2023 Aug 18;24(16):12930. doi: 10.3390/ijms241612930.
The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.
瞬时受体电位香草醛 3（TRPV3）钙离子通道对于维持皮肤健康至关重要，并且与各种皮肤相关疾病有关。由于 TRPV3 参与了皮肤炎症的发展，抑制 TRPV3 可能是一种潜在的治疗策略。从 L. 提取物中分离出的 α-倒捻子素对皮肤健康具有多种积极影响；然而，其潜在机制尚不清楚。本研究探讨了 α-倒捻子素对 Olmsted 综合征相关 TRPV3 高活性突变体的 TRPV3 抑制特性及其对 TRPV3 诱导的细胞因子分泌和细胞死亡的影响。我们的研究结果表明，α-倒捻子素能有效抑制 TRPV3，IC 为 0.077±0.013 μM，对野生型和突变型 TRPV3 均有抑制作用。用 α-倒捻子素抑制 TRPV3 可减少钙离子内流和细胞因子释放，保护细胞免受 TRPV3 诱导的死亡。这些结果表明，α-倒捻子素减轻了 TRPV3 激活的皮肤角质形成细胞中的炎症，表明 α-倒捻子素可潜在用于改善炎症性皮肤状况，如皮炎。
