The Mechanism of Fructus Trichosanthes Peel Extract Improving Heart Failure by Regulating Mitochondrial Division and Autophagy through AMPK/mTOR Pathway
JU Ling
ZHOU Yutian
SHI Lun
Abstract：Objective:To explore the mechanism of fructus trichosanthes peel extract(FTPE)improving heart failure by regulating mitochondrial division and autophagy through adenylate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.Methods:The fifty-eight rats were divided into control group,sham operation group,model group,positive control group(captopril 13.5 mg/kg)and FTPE group(fructus trichosanthes peel injection 4 mL/kg),with an intervention time of 8 weeks.Cardiac color ultrasonography[left ventricular ejection fraction(LVEF),left ventricular short axis reduction rate(LVFS),and left ventricular end-diastolic volume(LVEDV)]were examined.The myocardial histopathology,mitochondrial adenosine triphosphate(ATP),and reactive oxygen species(ROS)content were tested.The expression levels of AMPK/mTOR pathway,mitochondrial division and autophagy were detected by Western Blot.Results:After 4 weeks,compared with sham operation group,LVEF and LVFS were decreased and LVEDV was increased in model group,the difference was statistically significant(P＜0.05).After 12 weeks,compared with sham operation group,the levels of LVEF,LVFS,mitochondrial ATP and phosphorylated AMPK(p-AMPK)/AMPK protein in model group were decreased,while the expressions of LVEDV,ROS and mitochondrial fission 1 protein 1(Fis1),dynein-related protein 1(Drp1),autophagy associated gene 1(Beclin1),microtubule-associated protein 1 light chain 3(LC3)and phosphorylated mTOR(p-mTOR)/mTOR protein were increased(P＜0.05).Compared with model group,the expressions of LVEF,LVFS,mitochondrial ATP and P-AMPK/AMPK were increased in positive control group and FTPE group,while the expressions of LVEDV,ROS and myocardial Fis1,Drp1,Beclin1,LC3 and p-mTOR/mTOR protein were decreased(P＜0.05).Conclusion:The fructus trichosanthes peel extract could regulate mitochondrial division and autophagy by activating AMPK/mTOR,and improve cardiac function in rats with heart failure.
Keywords：heart failurefructus trichosanthis peel extractmitochondriasplitautophagyadenylate activated protein kinase/mammalian target of rapamycin pathwayratsexperimental study
Publication Date：2025-05-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1482-1487 )