Protective effect of the active component DMDD from <italic style="font-style: italic">Averrhoa carambola </italic>root on myocardial injury in diabetic mice and its correlation with the NCOA4/FTH1/ATG8 axis

CHEN Yongxin; LI Yuxuan; GU Kailei; YOU Jiajun; SUN Xiaohan; MA Jing; ZHOU Yanping; WEI Xiaojie

doi:10.6039/j.issn.1001-0408.2026.09.06

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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

更新时间：2026-05-14

- 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
- ZHONGGUO YAOFANG Vol. 37, Issue 9, Pages: 1141-1147(2026)
- 作者机构：
  
  广西中医药大学基础医学院生理学教研室，南宁　530200
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2026.09.06
  CLC： R965;R285
- Received：08 January 2026，
  
  Revised：2026-03-18，
  
  Accepted：20 April 2026，
  
  Published：15 May 2026
- 稿件说明：
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陈永欣,李宇轩,顾凯磊,等.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 [J].中国药房,2026,37(09):1141-1147.

CHEN Yongxin,LI Yuxuan,GU Kailei,et al.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[J].ZHONGGUO YAOFANG,2026,37(09):1141-1147.
陈永欣,李宇轩,顾凯磊,等.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 [J].中国药房,2026,37(09):1141-1147. DOI： 10.6039/j.issn.1001-0408.2026.09.06.

CHEN Yongxin,LI Yuxuan,GU Kailei,et al.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[J].ZHONGGUO YAOFANG,2026,37(09):1141-1147. DOI： 10.6039/j.issn.1001-0408.2026.09.06.

摘要

目的

基于核受体共激活因子4/铁蛋白重链1/自噬相关蛋白8（NCOA4/FTH1/ATG8）轴探讨杨桃根活性成分2-十二烷基-6-甲氧基-2，5-二烯-1，4-环己二酮（DMDD）对糖尿病小鼠心肌损伤的保护作用。

方法

将造模成功的糖尿病小鼠随机分为模型组和DMDD低、中、高剂量组（12.5、25、50 mg/kg），另设不造模的对照组，每组6只。各组小鼠分别灌胃相应药液或生理盐水，每天1次，连续21 d。给药结束后，检测小鼠空腹血糖（FBG）、血清中乳酸脱氢酶（LDH）及肌酸激酶同工酶MB（CK-MB）水平；观察心肌病理变化、纤维化程度及心肌细胞超微结构；检测心肌细胞死亡指数、NCOA4蛋白阳性指数；检测心肌组织中NCOA4、FTH1、ATG8、溶质载体家族7成员11（SLC7A11）及谷胱甘肽过氧化物酶4（GPX4）蛋白表达水平。

结果

与模型组比较，DMDD各剂量组小鼠心肌损伤明显缓解，心肌细胞超微结构亦有不同程度改善；小鼠FBG，血清中LDH、CK-MB水平，心肌细胞死亡指数、NCOA4蛋白阳性指数，心肌组织中NCOA4、FTH1、ATG8蛋白表达水平均显著降低（

＜0.001），而SLC7A11、GPX4蛋白表达水平均显著升高（

＜0.001）。

结论

DMDD可降低糖尿病小鼠血糖水平，减轻心肌组织病理损伤，并抑制细胞死亡，其机制与抑制NCOA4/FTH1/ATG8轴过度激活、减少铁自噬有关。

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 （

＜0.001）， while the protein expression levels of SLC7A11 and GPX4 were significantly increased （

＜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.

关键词

Keywords

references

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