Tanshinone IIA inhibits H2O2-induced ferroptosis in melanocytes through activating Nrf2 signaling pathway.

IF 2.9 4区医学 Q2 PHARMACOLOGY & PHARMACY Pharmacology Pub Date : 2024-10-16 DOI:10.1159/000541177

Xiaosha Li, Shiyang Tang, Haizhen Wang, Xin Li

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Abstract

Introduction: Melanocyte ferroptosis has been proven to contribute to the development of vitiligo. Tanshinone IIA (TSA), a Chinese herbal extract, has been shown to inhibit vitiligo progression. Whether TSA regulates ferroptosis in melanocytes remains unclear.

Methods: Hydrogen peroxide (H2O2) was used to induce melanocytes to stimulate vitiligo cell model in vitro. Cell proliferation was examined by 5-ethynyl-2'-deoxyuridine assay. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione peroxidase (GSH) and iron (Fe2+) were detected by corresponding commercial kit. The protein levels of ferroptosis-related markers and Nrf2 pathway-related markers were examined using western blot and immunofluorescence staining. Cell viability and cytotoxicity were analyzed using cell counting kit 8 assay and lactate dehydrogenase (LDH) detection. Mitochondrial morphology was examined using a transmission electron microscope.

Results: After H2O2 treatment, melanocyte proliferation was reduced, while oxidative stress and ferroptosis were enhanced. TSA treatment could inhibit ferroptosis in H2O2-induced melanocytes. Besides, TSA could activate Nrf2 pathway and promote Nrf2 nuclear translocation, and Nrf2 specific inhibitor (ML385) also reversed the inhibitory effect of TSA on H2O2-induced melanocyte ferroptosis.

Conclusion: Our data showed that TSA alleviated H2O2-induced melanocyte ferroptosis via activating Nrf2 pathway.

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丹参酮 IIA 可通过激活 Nrf2 信号通路抑制 H2O2 诱导的黑色素细胞铁突变。

简介黑色素细胞铁蛋白沉着已被证实是导致白癜风发病的原因之一。丹参酮 IIA（TSA）是一种中药提取物，已被证明可抑制白癜风的发展。方法：用过氧化氢（H2O2）在体外诱导黑色素细胞刺激白癜风细胞模型。细胞增殖采用 5-乙炔基-2'-脱氧尿苷检测法。丙二醛（MDA）、活性氧（ROS）、谷胱甘肽过氧化物酶（GSH）和铁（Fe2+）的水平由相应的商业试剂盒检测。采用 Western 印迹和免疫荧光染色法检测铁突变相关标记物和 Nrf2 通路相关标记物的蛋白水平。使用细胞计数试剂盒 8 和乳酸脱氢酶（LDH）检测分析细胞活力和细胞毒性。使用透射电子显微镜检查线粒体形态：结果：H2O2 处理后，黑色素细胞增殖减少，氧化应激和铁凋亡增强。TSA 可抑制 H2O2 诱导的黑色素细胞的铁突变。此外，TSA能激活Nrf2通路并促进Nrf2核转位，Nrf2特异性抑制剂（ML385）也能逆转TSA对H2O2诱导的黑色素细胞铁突变的抑制作用：结论：我们的研究数据表明，TSA通过激活Nrf2通路缓解了H2O2诱导的黑色素细胞铁突变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacology 医学-药学

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.