Chen Weimin, Li Shanshan, Li Jinwei, Zhou Wen, Wu Shouhai, Xu Shengmei, Cui Ke, Zhang Donna D, Liu Bo
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China;
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona, USA; and.
FASEB J. 2016 Jul;30(7):2500-10. doi: 10.1096/fj.201500109R. Epub 2016 Mar 22.
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant response and xenobiotic metabolism. Activation of the Nrf2 signaling pathway has been demonstrated to confer protection against environmental insults and prevent disease or inhibit the progression of diseases related to oxidative stress. In an attempt to identify novel improved Nrf2 inducers for systemic protection against tissue damage by environmental insults, we identified artemisitene as a novel Nrf2 activator using antioxidant responsive element luciferase assay in MDA-MB-231 cells. Further studies suggest that artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. In Nrf2 wild-type mice, systemic administration of artemisitene strongly inhibits bleomycin-induced lung damage. Artemisitene represents a novel class of Nrf2 inducer, and artemisitene-based therapeutic approach targeting Nrf2 may also provide antioxidant protection for humans against tissue damage by toxic chemicals.-Chen, W., Li, S., Li, J., Zhou, W., Wu, S., Xu, S., Cui, K., Zhang, D. D., Liu, B. Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury.
转录因子核因子红细胞2相关因子2（Nrf2）是细胞抗氧化反应和外源性物质代谢的关键调节因子。Nrf2信号通路的激活已被证明可提供针对环境损伤的保护作用，并预防疾病或抑制与氧化应激相关的疾病进展。为了寻找新型的、能提供更好全身保护作用以抵御环境损伤所致组织损伤的Nrf2诱导剂，我们在MDA-MB-231细胞中利用抗氧化反应元件荧光素酶测定法，将青蒿烯鉴定为一种新型的Nrf2激活剂。进一步的研究表明，青蒿烯通过减少Nrf2泛素化并增加其稳定性来激活Nrf2。在Nrf2野生型小鼠中，全身性给予青蒿烯可强烈抑制博来霉素诱导的肺损伤。青蒿烯代表了一类新型的Nrf2诱导剂，基于青蒿烯靶向Nrf2的治疗方法也可能为人类提供针对有毒化学物质所致组织损伤的抗氧化保护作用。——陈，W.，李，S.，李，J.，周，W.，吴，S.，徐，S.，崔，K.，张，D.D.，刘，B. 青蒿烯激活Nrf2依赖性抗氧化反应并保护免受博来霉素诱导的肺损伤
