QiShenYiQi dripping pill alleviates myocardial ischemia-induced ferroptosis via improving mitochondrial dynamical homeostasis and biogenesis
QiShenYiQi dripping pill alleviates myocardial ischemia-induced ferroptosis via improving mitochondrial dynamical homeostasis and biogenesis
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DOI：
10.1016/j.jep.2023.116282
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发表时间：
2023-02-22
影响因子：
5.4
通讯作者：
Li，Fang
中科院分区：
文献类型：
--
作者：
Wu，Lingling;Fan，Zhaoyang;Li，Fang
Ethnopharmacological relevanceQiShenYiQi is a Chinese herbal formula composed ofAstragalus membranaceusFisch. ex Bunge, root;Slauia miltiorrhiza Bunge, root and rhizome;Panax notoginseng(Burkill) F.H.Chen, root; andDalbergiaodorifera T.C.Chen, heartwood of trunk and root with a proportion of 10:5:1:0.067. Its dripping pills were approved by the National Medical Products Administration (NMPA) in 2003 and could be used in the clinical treatment of ischemic heart diseases. Ferroptosis is an important pathological mechanism in the process of myocardial ischemia (MI). Whether QSYQ can improve ferroptosis induced by myocardial ischemia is still unclear.Aim of the studyIn this study, the potential mechanisms of QSYQ against ferroptosis in MI-induced injury were investigated.Materials and methodsThe main components of QSYQ were analyzed by HPLC-Q-TOF-MS/MS. MI model was established by ligation of the left anterior descending coronary artery and then treated with QSYQ dropping pills for 14 days. The cardiac function of mice was evaluated by echocardiography. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to detect the pathological changes in heart tissue. Serum biochemical indexes were analyzed by biochemical kit. Transmission electron microscope (TEM) was used to observe the mitochondria ultrastructure and mitochondrial ROS was detected by immunofluorescence. Then, photoacoustic imaging was used to observe the redox status of the mice’ hearts. Finally, the mitochondrial dynamics and biogenesis related proteins and the proteins of ferroptosis were analyzed by western blotting. RT-PCR was used to detect the mRNA expression changes of ferroptosis.ResultsA total of 20 principal components of QSYQ were characterized by HPLC-Q-TOF-MS/MS. QSYQ significantly improved cardiac function and myocardial injury in MI mice. Furthermore, the lipid peroxidation change levels (MDA, 4-HNE, and GSH) in serum were attenuated and myocardial iron content was reduced after QSYQ treatment. On this basis, QSYQ also improved the expression changes of ferroptosis related mRNA and proteins. In addition, QSYQ promoted mitochondrial biogenesis (PGC-1α, Nrf1, and TFAM) and mitochondrial fusion (MFN-2 and OPA1) and inhibited mitochondrial excessive fission (Phosphorylation of Drp1 at ser616)in vitroandin vivo, indicating that the cardioprotection of QSYQ might be related to promoting mitochondrial biogenesis and dynamic homeostasis.ConclusionIn summary, QSYQ could alleviate MI-induced ferroptosis by improving mitochondrial biogenesis and dynamic homeostasis.
