Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2024-05, Vol.12 (5), p.e1229-n/a
• Main Authors: Zhang, Meng, Zhi, Deyuan, Liu, Pei, Wang, Yajun, Duan, Meili
• Format: Article
• Language: English
• Subjects: Adapter proteins; Animals; Apoptosis; Apoptosis - drug effects; Cardiomyocytes; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathies - prevention & control; Cardiomyopathy; Cell Line; Cytokines; Dioscin; Diosgenin - analogs & derivatives; Diosgenin - pharmacology; Diosgenin - therapeutic use; Disease Models, Animal; Ethanol; Heart; Hemodynamics; Inflammation; Kinases; lipopolysaccharide; Lipopolysaccharides; Male; MyD88; Myeloid Differentiation Factor 88 - metabolism; Original; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Sepsis; Sepsis - complications; Sepsis - drug therapy; Sepsis - metabolism; sepsis‐induced cardiomyopathy; Signal Transduction - drug effects; TLR4; Toll-Like Receptor 4 - metabolism; Transcription Factor RelA - metabolism; Tumor necrosis factor-TNF
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.1229

Background Dioscin has many pharmacological effects; however, its role in sepsis‐induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model. Methods The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4‐Hydroxy‐2‐nonenal (4‐HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B‐cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated‐p65 (p‐p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real‐time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and dihydroethidium staining assays. Results Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4‐HNE level in SIC rats. Dioscin reversed LPS‐induced reduction on SOD, CAT, GSH, and Bcl‐2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p‐p65/p65 value in LPS‐induced H9c2 cells. Conclusion Protective effects of Dioscin against LPS‐induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway. (1) Dioscin improved the myocardial tissue damage of SIC rat. (2) Dioscin improved LPS‐decreased the activities of SOD, CAT, and GSH. (3) Overexpressed TLR4 promoted the Dioscin‐suppressed the viability of H9c2 cell.