Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage
<i>Background and Objectives</i>: With the growing incidence and disability associated with myocardial infarction (MI), there is an increasing focus on cardiac rehabilitation post-MI. Kuanxiongzhuyu decoction (KXZY), a traditional Chinese herbal formula, has been used in the rehabilitati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/10/1740 |
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| author | Yihao Wu Miaofu Li Liuying Chen Linhao Xu Yizhou Xu Yigang Zhong |
| author_facet | Yihao Wu Miaofu Li Liuying Chen Linhao Xu Yizhou Xu Yigang Zhong |
| author_sort | Yihao Wu |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: With the growing incidence and disability associated with myocardial infarction (MI), there is an increasing focus on cardiac rehabilitation post-MI. Kuanxiongzhuyu decoction (KXZY), a traditional Chinese herbal formula, has been used in the rehabilitation of patients after MI. However, the chemical composition, protective effects, and underlying mechanism of KXZY remain unclear. <i>Materials and Methods</i>: In this study, the compounds in KXZY were identified using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) analytical method. Based on the compounds identified in the KXZY, we predictively selected the potential targets of MI and then constructed a protein–protein interaction (PPI) network to identify the key targets. Furthermore, the DAVID database was used for the GO and KEGG analyses, and molecular docking was used to verify the key targets. Finally, the cardioprotective effects and mechanism of KXZY were investigated in post-MI mice. <i>Results</i>: A total of 193 chemical compounds of KXZY were identified by HPLC-MS. In total, 228 potential targets were obtained by the prediction analysis. The functional enrichment studies and PPI network showed that the targets were largely associated with AKT-pathway-related apoptosis. The molecular docking verified that isoguanosine and adenosine exhibited excellent binding to the AKT. In vivo, KXZY significantly alleviated cardiac dysfunction and suppressed AKT phosphorylation. Furthermore, KXZY significantly increased the expression of the antiapoptotic proteins Bcl-2 and Bcl-xl and decreased the expression of the proapoptotic protein BAD. <i>Conclusions</i>: In conclusion, the network pharmacological and experimental evidence suggests that KXZY manifests anti-cardiac dysfunction behavior by alleviating cardiomyocyte apoptosis via the AKT pathway in MI and, thus, holds promising therapeutic potential. |
| first_indexed | 2024-03-10T21:04:32Z |
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| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-10T21:04:32Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
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| series | Medicina |
| spelling | doaj.art-323e32c948b14b4fa9a03bf38cfa86a72023-11-19T17:16:30ZengMDPI AGMedicina1010-660X1648-91442023-09-015910174010.3390/medicina59101740Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction DamageYihao Wu0Miaofu Li1Liuying Chen2Linhao Xu3Yizhou Xu4Yigang Zhong5Department of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, ChinaDepartment of Cardiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China<i>Background and Objectives</i>: With the growing incidence and disability associated with myocardial infarction (MI), there is an increasing focus on cardiac rehabilitation post-MI. Kuanxiongzhuyu decoction (KXZY), a traditional Chinese herbal formula, has been used in the rehabilitation of patients after MI. However, the chemical composition, protective effects, and underlying mechanism of KXZY remain unclear. <i>Materials and Methods</i>: In this study, the compounds in KXZY were identified using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) analytical method. Based on the compounds identified in the KXZY, we predictively selected the potential targets of MI and then constructed a protein–protein interaction (PPI) network to identify the key targets. Furthermore, the DAVID database was used for the GO and KEGG analyses, and molecular docking was used to verify the key targets. Finally, the cardioprotective effects and mechanism of KXZY were investigated in post-MI mice. <i>Results</i>: A total of 193 chemical compounds of KXZY were identified by HPLC-MS. In total, 228 potential targets were obtained by the prediction analysis. The functional enrichment studies and PPI network showed that the targets were largely associated with AKT-pathway-related apoptosis. The molecular docking verified that isoguanosine and adenosine exhibited excellent binding to the AKT. In vivo, KXZY significantly alleviated cardiac dysfunction and suppressed AKT phosphorylation. Furthermore, KXZY significantly increased the expression of the antiapoptotic proteins Bcl-2 and Bcl-xl and decreased the expression of the proapoptotic protein BAD. <i>Conclusions</i>: In conclusion, the network pharmacological and experimental evidence suggests that KXZY manifests anti-cardiac dysfunction behavior by alleviating cardiomyocyte apoptosis via the AKT pathway in MI and, thus, holds promising therapeutic potential.https://www.mdpi.com/1648-9144/59/10/1740Kuanxiongzhuyu decoctionpost-MInetwork pharmacology |
| spellingShingle | Yihao Wu Miaofu Li Liuying Chen Linhao Xu Yizhou Xu Yigang Zhong Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage Medicina Kuanxiongzhuyu decoction post-MI network pharmacology |
| title | Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage |
| title_full | Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage |
| title_fullStr | Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage |
| title_full_unstemmed | Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage |
| title_short | Utilizing a Combination of Network Pharmacology and Experimental Validation to Unravel the Mechanism by Which Kuanxiongzhuyu Decoction Ameliorates Myocardial Infarction Damage |
| title_sort | utilizing a combination of network pharmacology and experimental validation to unravel the mechanism by which kuanxiongzhuyu decoction ameliorates myocardial infarction damage |
| topic | Kuanxiongzhuyu decoction post-MI network pharmacology |
| url | https://www.mdpi.com/1648-9144/59/10/1740 |
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