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Inflammation
Erschienen in: Inflammation 5/2023

23.05.2023 | RESEARCH

Matrine Alleviates Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis and Apoptosis

verfasst von: Yuhong Xiao, Yun Yu, Longlong Hu, Yuhui Yang, Ye Yuan, Wenjun Zhang, Jun Luo, Lingling Yu

Erschienen in: Inflammation | Ausgabe 5/2023

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Abstract

Matrine is a Sophora alkaloid that exerts antitumor effects on a variety of diseases, but few studies have investigated the role of matrine in sepsis-induced myocardial injury. In the present study, we investigated the effects of matrine on septic myocardial injury and the potential mechanisms. Network pharmacology approaches were used to predict the targets of matrine in the treatment of sepsis-induced myocardial injury. A mouse sepsis-induced myocardial injury model was established to determine the effect of matrine. Mouse cardiac function was evaluated by ultrasonography, and cardiac morphology and cardiomyocyte apoptosis were evaluated by HE and TUNEL staining. Oxidative stress was assessed by measuring ROS levels and MDA and SOD activity. Bax, Bcl2, GPX4, ACSL4, PI3K, and AKT protein levels were evaluated by immunohistochemical staining and western blotting. Bioinformatics analysis identified that the potential therapeutic effect of matrine on sepsis-induced myocardial injury is closely related to ferroptosis and apoptosis regulation and showed significant involvement of the PI3K/AKT signaling pathway. In vivo, the matrine group showed improved myocardial function, morphology, and apoptosis ratio and alleviated oxidative stress compared with the LPS group, whereas 25 mg/kg matrine exerted the optimal inhibitory effect. Matrine alleviated LPS-induced cardiomyocyte ferroptosis and apoptosis, resulting in upregulation of Bax/Bcl2 and GPX4 expression and downregulation of ferroptosis marker protein (ACSL4) expression, as shown by immunohistochemistry and western blotting. Moreover, matrine increased PI3K/AKT pathway-related molecule expression and thus modulated ferroptosis and apoptosis. Matrine regulates PI3K/AKT pathway activity to inhibit apoptosis and ferroptosis and thereby alleviates sepsis-induced myocardial injury.
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Metadaten
Titel
Matrine Alleviates Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis and Apoptosis
verfasst von
Yuhong Xiao
Yun Yu
Longlong Hu
Yuhui Yang
Ye Yuan
Wenjun Zhang
Jun Luo
Lingling Yu
Publikationsdatum
23.05.2023
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 5/2023
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01833-2

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