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丹皮酚通过激活 Nrf2 信号通路保护黑素细胞免受过氧化氢诱导的氧化应激。

Paeonol protects melanocytes against hydrogen peroxide-induced oxidative stress through activation of Nrf2 signaling pathway.

机构信息

Dermatological Department, Urumqi Hospital of Traditional Chinese Medicine, Urumqi, China.

Dermatological Department, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, China.

出版信息

Drug Dev Res. 2021 Sep;82(6):861-869. doi: 10.1002/ddr.21793. Epub 2021 Jan 24.

DOI:10.1002/ddr.21793
PMID:33491230
Abstract

Oxidative stress plays a pivotal role in the pathogenesis of vitiligo. Paeonol, a phenolic compound found in the root bark of Cortex Moutan, has been suggested to have therapeutic effects on various diseases through nuclear factor Nrf2 mediated antioxidant pathways. However, the therapeutic effects of paeonol on vitiligo have not been investigated. In this study, we investigated whether paeonol could protect melanocytes against oxidative stress through Nrf2 activation. Hydrogen peroxide (H O ) was used to mimic the oxidative stress. PIG1 cells were pretreated with paeonol for 24 h, and then were treated with H O for 24 h. To detect the role of Nrf2, siRNA method was used to knockdown the Nrf2 expression. After that, cell viability, melanin content, tyrosinase activity, intracellular reactive oxygen species, antioxidant enzymes activities, nuclear translocation of Nrf2, and mRNA expression of Nrf2 downstream antioxidant genes were detected. Paeonol improved cell viability and melanogenesis in PIG1 cells treated with H O . Paeonol also alleviated oxidative stress by restoring the activities of superoxide dismutase, catalase, and glutathione peroxidase. Paeonol promoted Nrf2 nuclear translocation and the expression of its downstream-regulated antioxidative genes under oxidative stress. Furthermore, Nrf2 knockdown by siRNA abolished the protective effects of paeonol on PIG1 cells against oxidative damage. Paeonol protected melanocytes against H O -induced oxidative stress by Nrf2 mediated antioxidant pathways. Paeonol is a potential therapeutic drug for vitiligo.

摘要

氧化应激在白癜风的发病机制中起着关键作用。丹皮酚是从牡丹皮中提取的一种酚类化合物,据报道,它通过核因子 Nrf2 介导的抗氧化途径对多种疾病具有治疗作用。然而,丹皮酚对白癜风的治疗作用尚未得到研究。在这项研究中,我们研究了丹皮酚是否可以通过激活 Nrf2 来保护黑素细胞免受氧化应激。我们使用过氧化氢 (H2O2) 来模拟氧化应激。将 PIG1 细胞用丹皮酚预处理 24 小时,然后用 H2O2 处理 24 小时。为了检测 Nrf2 的作用,我们使用 siRNA 方法敲低了 Nrf2 的表达。之后,检测细胞活力、黑色素含量、酪氨酸酶活性、细胞内活性氧、抗氧化酶活性、Nrf2 的核转位以及 Nrf2 下游抗氧化基因的 mRNA 表达。丹皮酚改善了 H2O2 处理的 PIG1 细胞的细胞活力和黑色素生成。丹皮酚还通过恢复超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性来减轻氧化应激。丹皮酚在氧化应激下促进 Nrf2 的核转位和其下游调节抗氧化基因的表达。此外,siRNA 敲低 Nrf2 消除了丹皮酚对 PIG1 细胞对抗氧化损伤的保护作用。丹皮酚通过 Nrf2 介导的抗氧化途径保护黑素细胞免受 H2O2 诱导的氧化应激。丹皮酚是治疗白癜风的一种潜在治疗药物。

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