Protective effect of the active component DMDD from Averrhoa carambola root on myocardial injury in diabetic mice and its correlation with the NCOA4/FTH1/ATG8 axis
- VernacularTitle:杨桃根活性成分DMDD对糖尿病小鼠心肌损伤的保护作用及其与NCOA4/FTH1/ATG8轴的相关性研究
- Author:
Yongxin CHEN
1
;
Yuxuan LI
1
;
Kailei GU
1
;
Jiajun YOU
1
;
Xiaohan SUN
1
;
Jing MA
1
;
Yanping ZHOU
1
;
Xiaojie WEI
1
Author Information
1. Dept. of Physiology，School of Basic Medical Sciences，Guangxi University of Chinese Medicine，Nanning 530200，China
- Publication Type:Journal Article
- Keywords:
Averrhoa carambola root;
DMDD;
NCOA4/FTH1/ATG8 axis;
diabetic cardiomyopathy;
ferritinophagy
- From:
China Pharmacy
2026;37(9):1141-1147
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2，5-diene-1，4-cyclohexanedione （DMDD）， an active component from Averrhoa carambola root， on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 （NCOA4/FTH1/ATG8） axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-， medium-， and high-dose （12.5， 25， 50 mg/kg） groups， while an additional non-modeled control group was established， with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration， the levels of fasting blood glucose （FBG）， serum lactate dehydrogenase （LDH）， and creatine kinase isoenzyme MB （CK-MB） were measured. Myocardial pathological changes， degree of fibrosis， and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4， FTH1， ATG8， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） in cardiac tissue were measured. RESULTS Compared with model group， each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels， the myocardial cell death index and NCOA4 protein positive index，the protein expression levels of NCOA4， FTH1， and ATG8 in cardiac tissue were significantly decreased （ P ＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （ P ＜0.001）. CONCLUSIONS DMDD can reduce blood glucose levels， alleviate myocardial histopathological injury， and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.
