RT Journal Article
SR Electronic
T1 Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201667
DO 10.26508/lsa.202201667
VO 6
IS 1
A1 Wang, Tian-Xiang
A1 Duan, Kun-Long
A1 Huang, Zi-Xuan
A1 Xue, Zi-An
A1 Liang, Jun-Yun
A1 Dang, Yongjun
A1 Zhang, Ao
A1 Xiong, Yue
A1 Ding, Chunyong
A1 Guan, Kun-Liang
A1 Yuan, Hai-Xin
YR 2023
UL https://www.life-science-alliance.org/content/6/1/e202201667.abstract
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.