Integrated multiomics reveal mechanism of Aidi Injection in attenuating doxorubicin-induced cardiotoxicity.
10.19540/j.cnki.cjcmm.20250113.301
- Author:
Yan-Li WANG
1
;
Yu-Jie TU
1
;
Jian-Hua ZHU
1
;
Lin ZHENG
2
;
Yong HUANG
2
;
Jia SUN
2
;
Yong-Jun LI
3
;
Jie PAN
2
;
Chun-Hua LIU
4
;
Yuan LU
5
Author Information
1. State Key Laboratory of Functions and Applications of Medicinal Plants/Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University Guiyang 550004,China School of Pharmaceutical Sciences,Guizhou Medical University Guiyang 550004,China.
2. State Key Laboratory of Functions and Applications of Medicinal Plants/Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University Guiyang 550004,China.
3. Engineering Research Center for the Development and Application of Ethnic Medicine and TCM(Ministry of Education),Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Guizhou Medical University Guiyang 550004,China School of Pharmaceutical Sciences,Guizhou Medical University Guiyang 550004,China.
4. Engineering Research Center for the Development and Application of Ethnic Medicine and TCM(Ministry of Education),Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Guizhou Medical University Guiyang 550004,China.
5. State Key Laboratory of Functions and Applications of Medicinal Plants/Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University Guiyang 550004,China Engineering Research Center for the Development and Application of Ethnic Medicine and TCM(Ministry of Education),Guizhou Provincial Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Guizhou Medical University Guiyang 550004,China.
- Publication Type:Journal Article
- Keywords:
Aidi Injection;
cardiotoxicity;
doxorubicin;
metabolomics;
proteomics;
transcriptomics
- MeSH:
Doxorubicin/toxicity*;
Animals;
Mice;
Cardiotoxicity/genetics*;
Drugs, Chinese Herbal/administration & dosage*;
Male;
Proteomics;
Metabolomics;
Injections;
Humans;
Multiomics
- From:
China Journal of Chinese Materia Medica
2025;50(8):2245-2259
- CountryChina
- Language:Chinese
-
Abstract:
The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
