PT  - JOURNAL ARTICLE
AU  - Wang, Tian-Xiang
AU  - Duan, Kun-Long
AU  - Huang, Zi-Xuan
AU  - Xue, Zi-An
AU  - Liang, Jun-Yun
AU  - Dang, Yongjun
AU  - Zhang, Ao
AU  - Xiong, Yue
AU  - Ding, Chunyong
AU  - Guan, Kun-Liang
AU  - Yuan, Hai-Xin
TI  - Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis
AID  - 10.26508/lsa.202201667
DP  - 2023 Jan 01
TA  - Life Science Alliance
PG  - e202201667
VI  - 6
IP  - 1
4099  - http://www.life-science-alliance.org/content/6/1/e202201667.short
4100  - http://www.life-science-alliance.org/content/6/1/e202201667.full
SO  - Life Sci. Alliance2023 Jan 01; 6
AB  - Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from Salvia miltiorrhiza (Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.