Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin
Doxorubicin (DOX) can induce myocardial energy metabolism disorder and further worsen heart failure. “Energy protection” is proposed as a new cardiac protection strategy. Previous studies have found that Di’ao Xinxuekang (DXXK) can improve doxorubicin-induced cardiotoxicity in mice by inhibiting fer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/897 |
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| author | Tao Wang Chuqiao Yuan Jia Liu Liangyan Deng Wei Li Junling He Honglin Liu Liping Qu Jianming Wu Wenjun Zou |
| author_facet | Tao Wang Chuqiao Yuan Jia Liu Liangyan Deng Wei Li Junling He Honglin Liu Liping Qu Jianming Wu Wenjun Zou |
| author_sort | Tao Wang |
| collection | DOAJ |
| description | Doxorubicin (DOX) can induce myocardial energy metabolism disorder and further worsen heart failure. “Energy protection” is proposed as a new cardiac protection strategy. Previous studies have found that Di’ao Xinxuekang (DXXK) can improve doxorubicin-induced cardiotoxicity in mice by inhibiting ferroptosis. However, there are very few studies associating DXXK and energy protection. This study aims to explore the “energy protection” effect of DXXK on cardiotoxicity induced by DOX. A DOX-induced cardiotoxicity model established in rats and H9c2 cells are used to analyze the therapeutic effects of DXXK on serum indexes, cardiac function indexes and cardiac histopathology. The metabonomic methods were used to explore the potential mechanism of DXXK in treating DOX-induced cardiotoxicity. In addition, we also observed the mitochondrial- and autophagy-related indicators of myocardial cells and the mRNA expression level of the core target regulating energy-metabolism-related pathways. Our results indicated that DXXK can improve cardiac function, reduce myocardial enzymes and alleviate the histological damage of heart tissue caused by DOX. In addition, DXXK can improve mitochondrial damage induced by DOX and inhibit excessive autophagy. Metabonomics analysis showed that DOX can significantly affects the pathways related to energy metabolism of myocardial cells, which are involved in the therapeutic mechanism of DXXK. In conclusion, DXXK can treat DOX-induced cardiotoxicity through the AMPK-mediated energy protection pathway. |
| first_indexed | 2024-03-09T12:28:50Z |
| format | Article |
| id | doaj.art-918da6ac69004af395f0bec1c3d5ab4f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:28:50Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-918da6ac69004af395f0bec1c3d5ab4f2023-11-30T22:32:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124289710.3390/ijms24020897Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by DoxorubicinTao Wang0Chuqiao Yuan1Jia Liu2Liangyan Deng3Wei Li4Junling He5Honglin Liu6Liping Qu7Jianming Wu8Wenjun Zou9State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaSchool of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaDoxorubicin (DOX) can induce myocardial energy metabolism disorder and further worsen heart failure. “Energy protection” is proposed as a new cardiac protection strategy. Previous studies have found that Di’ao Xinxuekang (DXXK) can improve doxorubicin-induced cardiotoxicity in mice by inhibiting ferroptosis. However, there are very few studies associating DXXK and energy protection. This study aims to explore the “energy protection” effect of DXXK on cardiotoxicity induced by DOX. A DOX-induced cardiotoxicity model established in rats and H9c2 cells are used to analyze the therapeutic effects of DXXK on serum indexes, cardiac function indexes and cardiac histopathology. The metabonomic methods were used to explore the potential mechanism of DXXK in treating DOX-induced cardiotoxicity. In addition, we also observed the mitochondrial- and autophagy-related indicators of myocardial cells and the mRNA expression level of the core target regulating energy-metabolism-related pathways. Our results indicated that DXXK can improve cardiac function, reduce myocardial enzymes and alleviate the histological damage of heart tissue caused by DOX. In addition, DXXK can improve mitochondrial damage induced by DOX and inhibit excessive autophagy. Metabonomics analysis showed that DOX can significantly affects the pathways related to energy metabolism of myocardial cells, which are involved in the therapeutic mechanism of DXXK. In conclusion, DXXK can treat DOX-induced cardiotoxicity through the AMPK-mediated energy protection pathway.https://www.mdpi.com/1422-0067/24/2/897cardiotoxicityenergy metabolismmitochondriondoxorubicinXinxuekang |
| spellingShingle | Tao Wang Chuqiao Yuan Jia Liu Liangyan Deng Wei Li Junling He Honglin Liu Liping Qu Jianming Wu Wenjun Zou Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin International Journal of Molecular Sciences cardiotoxicity energy metabolism mitochondrion doxorubicin Xinxuekang |
| title | Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin |
| title_full | Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin |
| title_fullStr | Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin |
| title_full_unstemmed | Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin |
| title_short | Targeting Energy Protection as a Novel Strategy to Disclose Di’ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin |
| title_sort | targeting energy protection as a novel strategy to disclose di ao xinxuekang against the cardiotoxicity caused by doxorubicin |
| topic | cardiotoxicity energy metabolism mitochondrion doxorubicin Xinxuekang |
| url | https://www.mdpi.com/1422-0067/24/2/897 |
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