Tianxiangdan(TXD) alleviates myocardial ischemia reperfusion-induced ferroptosis through the activation of estrogen receptor alpha(ERα)  

作　　者：Yuanjia Yue Yu Li Xing Rong Zhao Ji Huimin Wang Liang Chen Lin Jiang 

机构地区：[1]Department of Pharmacy,The Fourth College of Clinical Medicine,Xinjiang Medical University,Urumqi 830000,China [2]Department of Pharmacy,Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Urumqi 830000,China [3]State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University,Urumqi 830000,China [4]Department of Neurosurgery ICU,Xinjiang Uygur Autonomous Region People’s Hospital,Urumqi,830000,China

出　　处：《Chinese Journal of Natural Medicines》2025年第1期102-110,共9页中国天然药物(英文版)

基　　金：supported by the National Natural Science Foundation of China (No. 8196140154);the Natural Science Foundation of Xinjiang Uygur Autonomous Region (Nos.2023D01C139 and 2023D01C63);the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund (No. SKL-HIDCA-2020-8)。

摘　　要：Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.Highperformance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 compounds in TXD.Network pharmacological analysis predicted potential target genes and their modes of action.Cardiac function,ischaemic ST changes,lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD)activity,myocardial fiber,and infarct size were assessed using in vivo and in vitro I/R injury models.Estrogen receptor alpha(ERα)protein expression and estradiol(E2)levels were measured to confirm TXD's impact on estrogen levels and ERαexpression.To examine if TXD reduces I/R injury through ERα,an AZD group(300 nmol·L^(-1)AZD9496 and 15%TXD serum)was compared to a TXD group(15%TXD serum).The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway.I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0μmol·L^(-1)Fer-1 and 15%TXD serum)to elucidate the potential association between ferroptosis and ERαproteins.A DCFH-DA probe detected reactive oxygen species(ROS)and Fe^(2+),while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and preventing I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe^(2+)levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERαand glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritinheavy polypeptide 1(FTH1).The AZ group exhibited

关 键 词：TIANXIANGDAN Estrogen receptor alpha Ferroptosis Myocardial ischemia-reperfusion injury Network pharmacology 

分 类 号：R285.5[医药卫生—中药学]