Protective effect and potential mechanism of linderene against myocardial infarction

WEI Wei; GAO Ri-feng; HAN Wen-zheng; LYU Yang; ZHENG Shun-wen; QIU Xing-biao

doi:10.3969/j.issn.1672-5301.2025.08.016

Abstract：Objective To investigate the protective effect and mechanism of action of Linderene in the pathological process of myocardial infarction.Methods Construction of the mouse myocardial infarction model was completed in the laboratory of the Second Affiliated Hospital of Zhejiang University between April and December 2024.Following modelling,different concentrations of linderene were injected intraperitoneally into the mice once a day for three consecutive days.Use various staining and detection techniques such as echocardiography to evaluate the effect of Linderene on the progression of myocardial infarction.To analyse its regulatory effect on neutrophil aggregation and neutrophil extracellular trap formation(NETosis)phenomenon after myocardial infarction using various techniques such as citrullinated histone H3(citH3)immunofluorescence staining.An in vitro model of myocardial cell hypoxia was established and Western blot was used to detect the effect of Linderene on the expression level of dihydroorotate dehydrogenase(DHODH)protein in mitochondria.At the same time,multiple staining techniques were used to investigate its intervention effect on the ferroptosis process of myocardial cells.Establish a co-culture system to further validate the inhibitory effect of Linderene on NETosis in vitro.Result Linderene significantly reduced the area of myocardial infarction and effectively improved cardiac function.In the development process of myocardial infarction,Linderene has a significant inhibitory effect on ferroptosis in cardiomyocytes,and can also significantly reduce Reactive Oxygen Species(ROS)levels and lipid peroxidation levels.The partial protective mechanism of Linderene is through the up-regulation of the mitochondrial DHODH pathway,thereby exerting antioxidant and anti-ferroptotic effects.In addition,Linderene can effectively reduce the aggregation of neutrophils in the infarcted area and inhibit the formation of NETosis after MI.Conclusion Linderene can reduce the occurrence of ferroptosis in myocardial cells by upregulating the mitochondrial DHODH pathway,and reduce the aggregation of neutrophils and the formation of NETosis after myocardial infarction,thereby significantly reducing the area of myocardial infarction and providing a new potential strategy for the treatment of myocardial infarction.