Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction
Background: Doxorubicin (DOX) is an effective broad-spectrum antitumor drug, but its clinical application is limited due to the side effects of cardiac damage. Astragaloside IV (AS-IV) is a significant active component of Astragalus membranaceus that exerts cardioprotective effects through various p...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-03-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803045 |
| _version_ | 1797853540233773056 |
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| author | Xueheng Chen Chao Tian Zhiqiang Zhang Yiran Qin Runqi Meng Xuening Dai Yuanyuan Zhong Xiqing Wei Jinguo Zhang Cheng Shen |
| author_facet | Xueheng Chen Chao Tian Zhiqiang Zhang Yiran Qin Runqi Meng Xuening Dai Yuanyuan Zhong Xiqing Wei Jinguo Zhang Cheng Shen |
| author_sort | Xueheng Chen |
| collection | DOAJ |
| description | Background: Doxorubicin (DOX) is an effective broad-spectrum antitumor drug, but its clinical application is limited due to the side effects of cardiac damage. Astragaloside IV (AS-IV) is a significant active component of Astragalus membranaceus that exerts cardioprotective effects through various pathways. However, whether AS-IV exerts protective effects against DOX-induced myocardial injury by regulating the pyroptosis is still unknown and is investigated in this study. Methods: The myocardial injury model was constructed by intraperitoneal injection of DOX, and AS-IV was administered via oral gavage to explore its specific protective mechanism. Cardiac function and cardiac injury indicators, including lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and brain natriuretic peptide (BNP), and histopathology of the cardiomyocytes were assessed 4 weeks post DOX challenge. Serum levels of IL-1β, IL-18, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) and the expression of pyroptosis and signaling proteins were also determined. Results: Cardiac dysfunction was observed after the DOX challenge, as evidenced by reduced ejection fraction, increased myocardial fibrosis, and increased BNP, LDH, cTnI, and CK-MB levels (p < 0.05, N = 3–10). AS-IV attenuated DOX-induced myocardial injury. The mitochondrial morphology and structure were also significantly damaged after DOX treatment, and these changes were restored after AS-IV treatment. DOX induced an increase in the serum levels of IL-1β, IL-18, SOD, MDA and GSH as well as an increase in the expression of pyroptosis-related proteins (p < 0.05, N = 3–6). Besides, AS-IV depressed myocardial inflammatory-related pyroptosis via activation of the expressions of nuclear factor E2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) (p < 0.05, N = 3). Conclusions: Our results showed that AS-IV had a significant protective effect against DOX-induced myocardial injury, which may be associated with the activation of Nrf-2/HO-1 to inhibit pyroptosis. |
| first_indexed | 2024-04-09T19:51:11Z |
| format | Article |
| id | doaj.art-b1960f2b473741a2b89aa6cc1a9e6114 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-09T19:51:11Z |
| publishDate | 2023-03-01 |
| publisher | IMR Press |
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| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-b1960f2b473741a2b89aa6cc1a9e61142023-04-03T05:52:10ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-03-012834510.31083/j.fbl2803045S2768-6701(22)00731-6Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac DysfunctionXueheng Chen0Chao Tian1Zhiqiang Zhang2Yiran Qin3Runqi Meng4Xuening Dai5Yuanyuan Zhong6Xiqing Wei7Jinguo Zhang8Cheng Shen9Affiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaCheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaAffiliated Hospital of Jining Medical University, Clinical Medical College, Jining Medical University, 272000 Jining, Shandong, ChinaBackground: Doxorubicin (DOX) is an effective broad-spectrum antitumor drug, but its clinical application is limited due to the side effects of cardiac damage. Astragaloside IV (AS-IV) is a significant active component of Astragalus membranaceus that exerts cardioprotective effects through various pathways. However, whether AS-IV exerts protective effects against DOX-induced myocardial injury by regulating the pyroptosis is still unknown and is investigated in this study. Methods: The myocardial injury model was constructed by intraperitoneal injection of DOX, and AS-IV was administered via oral gavage to explore its specific protective mechanism. Cardiac function and cardiac injury indicators, including lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and brain natriuretic peptide (BNP), and histopathology of the cardiomyocytes were assessed 4 weeks post DOX challenge. Serum levels of IL-1β, IL-18, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) and the expression of pyroptosis and signaling proteins were also determined. Results: Cardiac dysfunction was observed after the DOX challenge, as evidenced by reduced ejection fraction, increased myocardial fibrosis, and increased BNP, LDH, cTnI, and CK-MB levels (p < 0.05, N = 3–10). AS-IV attenuated DOX-induced myocardial injury. The mitochondrial morphology and structure were also significantly damaged after DOX treatment, and these changes were restored after AS-IV treatment. DOX induced an increase in the serum levels of IL-1β, IL-18, SOD, MDA and GSH as well as an increase in the expression of pyroptosis-related proteins (p < 0.05, N = 3–6). Besides, AS-IV depressed myocardial inflammatory-related pyroptosis via activation of the expressions of nuclear factor E2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) (p < 0.05, N = 3). Conclusions: Our results showed that AS-IV had a significant protective effect against DOX-induced myocardial injury, which may be associated with the activation of Nrf-2/HO-1 to inhibit pyroptosis.https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803045astragalus membranaceusdoxorubicinpyroptosisnrf-2/ho-1cardiac dysfunctioncardioprotection |
| spellingShingle | Xueheng Chen Chao Tian Zhiqiang Zhang Yiran Qin Runqi Meng Xuening Dai Yuanyuan Zhong Xiqing Wei Jinguo Zhang Cheng Shen Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction Frontiers in Bioscience-Landmark astragalus membranaceus doxorubicin pyroptosis nrf-2/ho-1 cardiac dysfunction cardioprotection |
| title | Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction |
| title_full | Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction |
| title_fullStr | Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction |
| title_full_unstemmed | Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction |
| title_short | Astragaloside IV Inhibits NLRP3 Inflammasome-Mediated Pyroptosis via Activation of Nrf-2/HO-1 Signaling Pathway and Protects against Doxorubicin-Induced Cardiac Dysfunction |
| title_sort | astragaloside iv inhibits nlrp3 inflammasome mediated pyroptosis via activation of nrf 2 ho 1 signaling pathway and protects against doxorubicin induced cardiac dysfunction |
| topic | astragalus membranaceus doxorubicin pyroptosis nrf-2/ho-1 cardiac dysfunction cardioprotection |
| url | https://www.imrpress.com/journal/FBL/28/3/10.31083/j.fbl2803045 |
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