首页|Tianxiangdan(TXD)alleviates myocardial ischemia reperfusion-in-duced ferroptosis through the activation of estrogen receptor alpha(ERα)

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

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Tianxiangdan(TXD),a traditional Chinese herbal remedy,demonstrates efficacy in mitigating myocardial ischemia-reperfusion(I/R)-induced damage.This study employed network phar-macology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R.High-performance liquid chromatography-mass spectrometry(HPLC-MS)identified 86 com-pounds 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 estro-gen levels and ERα expression.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(1.0 μmol·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 Fe2+,while Western blotting assessed target protein expression.Both in vitro and in vivo experiments demon-strated that TXD attenuated I/R injury by reducing elevated ST-segment levels,improving cardiac injury biomarkers(LDH,MDA,and SOD),alleviating pathological features,and pre-venting I/R-induced loss of cell viability in vitro.The effects and mechanisms of TXD on I/R in-jury-associated ferroptosis were investigated using I/R-induced H9c2 cells.The TXD group showed significantly decreased ROS and Fe2+levels,while the AZ group(treated with AZD9496)exhibited increased levels.The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4(GPX4),with reduced levels of P53 protein and ferritin-heavy polypeptide 1(FTH1).The AZ group exhibited contrasting effects on these expression levels.The literature indicated a novel connection between ERα and ferroptosis.TXD activ-ates the ERα signaling pathway,promoting protection against I/R-induced myocardial cell ferroptosis.This study provides evidence supporting TXD use for myocardial ischemia treat-ment,particularly in older female patients who may benefit from its therapeutic outcomes.

TianxiangdanEstrogen receptor alphaFerroptosisMyocardial ischemia-reperfusion injuryNetwork pharmacology

Yuanjia Yue、Yu Li、Xing Rong、Zhao Ji、Huimin Wang、Liang Chen、Lin Jiang

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Department of Pharmacy,The Fourth College of Clinical Medicine,Xinjiang Medical University,Urumqi 830000,China

Department of Pharmacy,Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Urumqi 830000,China

State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University,Urumqi 830000,China

Department of Neurosurgery ICU,Xinjiang Uygur Autonomous Region People's Hospital,Urumqi,830000,China

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2025

10.1016/S1875-5364(25)60811-9

中国天然药物
中国药科大学,中国药学会

中国天然药物

影响因子：0.859
ISSN：1672-3651
年,卷(期)：2025.23(1)