Ameliorative effects of Imperatae Rhizoma extract against doxorubicin-induced myocardial injury and its molecular mechanisms
- VernacularTitle:白茅根提取物对多柔比星致心肌损伤的改善作用及分子机制
- Author:
Huan LUO
1
;
Qiang WANG
2
;
Youjun ZHU
1
;
Chunrong TAO
1
;
Yang MAO
3
;
Defeng LI
3
Author Information
1. Dept. of Cardiology，the Second Affiliated Hospital of Army Medical University，Chongqing 400037，China
2. Dept. of Pharmacy，the Second Affiliated Hospital of Army Medical University，Chongqing 400037，China
3. Clinical Medical Research Center，the Second Affiliated Hospital of Army Medical University，Chongqing 400037，China
- Publication Type:Journal Article
- Keywords:
Imperatae Rhizoma;
extract;
doxorubicin;
myocardial injury;
mitochondrial function;
estrogen receptor 1;
network pharmacology
- From:
China Pharmacy
2026;37(12):1559-1566
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the ameliorative effects of Imperatae Rhizoma （RI） extract against doxorubicin （DOX）-induced myocardial injury and its potential molecular mechanisms. METHODS Network pharmacology was employed to screen for target overlap between the predicted core targets of RI’s active components and targets associated with myocardial injury， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses. Based on the network pharmacology results， a DOX-induced myocardial injury mouse model was established using male C57BL/6J mice to observe the effects of RI extract [1 g/（kg·d）] on the survival rate， body weight， and cardiac damage. A DOX-injured HL-1 cardiomyocyte model was established to assess the effects of different mass concentrations of RI extract （50， 100， 200 μg/mL） on mitochondrial membrane potential， adenosine triphosphate （ATP） production， reactive oxygen species （ROS） generation， apoptosis， and expression of the relevant target proteins. The mechanism was validated by transfecting with small interfering RNA of estrogen receptor 1 （ESR1）. RESULTS A total of 58 overlapping targets were screened， which were enriched in biological processes such as hormone response and hypoxia response， as well as pathways including apoptosis， tricarboxylic acid cycle， and pyruvate metabolism. Key target proteins， such as ESR1， were also identified. Animal experiments confirmed that the survival rate of mice in the DOX+RI group was obviously higher than that in the DOX group， with a slower rate of weight loss and improved pathological changes， such as cardiac atrophy and inflammatory cell infiltration， compared to the DOX group. Cell experiments showed that， compared with the DOX group， the DOX+RI groups exhibited significantly increased or upregulated mitochondrial membrane potential， relative ATP levels， and mRNA expressions of isocitrate dehydrogenase 3A （IDH3A）， succinate dehydrogenase A （SDHA） and peroxisome proliferators-activated receptor γ coactivator-1α （PGC-1α）， as well as mRNA and protein expressions of ESR1； conversely， relative ROS levels and apoptosis rates were significantly reduced （ P ＜0.05）. Following ESR1 knockdown， the anti-apoptotic effect of the RI extract on cardiomyocytes was significantly attenuated （ P ＜0.05）. CONCLUSIONS The RI extract may alleviate DOX-induced myocardial injury by activating the ESR1 signaling pathway， improving mitochondrial function， and inhibiting excessive ROS production and cardiomyocyte apoptosis.
