Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway
The present study investigated whether quercetin promotes the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated the protective effects of quercetin against diabetic cardiomyopathy by anal...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2022/9723632 |
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| author | Zhang Wei Zhou Jing Kang Pinfang Shi Chao Qian Shaohuan |
| author_facet | Zhang Wei Zhou Jing Kang Pinfang Shi Chao Qian Shaohuan |
| author_sort | Zhang Wei |
| collection | DOAJ |
| description | The present study investigated whether quercetin promotes the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated the protective effects of quercetin against diabetic cardiomyopathy by analyzing the expression of pyroptosis pathway proteins, myocardial cell apoptosis rate, degree of myocardial fibrosis, and serum inflammatory indices in the hearts of model rats with diabetes. We evaluated the expression of Nrf2 in the nucleus of cardiomyocytes and H9C2 cells to clarify the role of quercetin in promoting the nuclear translocation of Nrf2. In addition, we coincubated cardiomyocytes with the Nrf2 inhibitor ML385 to confirm that quercetin inhibits the diabetes-induced cardiomyocyte pyroptosis via the Nrf2 pathway. We found that quercetin promoted the nuclear translocation of Nrf2 in cardiac cells of diabetic rats, increased the expression of the antioxidant proteins HO-1, GCLC, and SOD, reduced the accumulation of ROS and the degree of cardiomyocyte apoptosis, and alleviated diabetes-induced cardiac fibrosis. The therapeutic effects of quercetin were further validated in H9C2 cardiomyocytes. Interestingly, ML385 prevented the beneficial effects of quercetin on diabetic cardiomyopathy, further indicating that the quercetin-mediated inhibition of pyroptosis requires the participation of the Nrf2 pathway. In conclusion, quercetin promoted the nuclear translocation of Nrf2, increased the expression of antioxidant factors in cells, and inhibited the progression of cell pyroptosis, thereby alleviating diabetic cardiomyopathy. |
| format | Article |
| id | doaj-art-8049c737b56744dcace8d49e7e4122d2 |
| institution | Kabale University |
| issn | 2314-6753 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-8049c737b56744dcace8d49e7e4122d22025-02-03T06:01:49ZengWileyJournal of Diabetes Research2314-67532022-01-01202210.1155/2022/9723632Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 PathwayZhang Wei0Zhou Jing1Kang Pinfang2Shi Chao3Qian Shaohuan4Department of Cardiovascular Medicine of The First Affiliated Hospital of Bengbu Medical CollegeDepartment of Physiology of Bengbu Medical CollegeDepartment of Cardiovascular Medicine of The First Affiliated Hospital of Bengbu Medical CollegeDepartment of Cardiac Surgery of The First Affiliated Hospital of Bengbu Medical CollegeDepartment of Cardiovascular Medicine of The First Affiliated Hospital of Bengbu Medical CollegeThe present study investigated whether quercetin promotes the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated the protective effects of quercetin against diabetic cardiomyopathy by analyzing the expression of pyroptosis pathway proteins, myocardial cell apoptosis rate, degree of myocardial fibrosis, and serum inflammatory indices in the hearts of model rats with diabetes. We evaluated the expression of Nrf2 in the nucleus of cardiomyocytes and H9C2 cells to clarify the role of quercetin in promoting the nuclear translocation of Nrf2. In addition, we coincubated cardiomyocytes with the Nrf2 inhibitor ML385 to confirm that quercetin inhibits the diabetes-induced cardiomyocyte pyroptosis via the Nrf2 pathway. We found that quercetin promoted the nuclear translocation of Nrf2 in cardiac cells of diabetic rats, increased the expression of the antioxidant proteins HO-1, GCLC, and SOD, reduced the accumulation of ROS and the degree of cardiomyocyte apoptosis, and alleviated diabetes-induced cardiac fibrosis. The therapeutic effects of quercetin were further validated in H9C2 cardiomyocytes. Interestingly, ML385 prevented the beneficial effects of quercetin on diabetic cardiomyopathy, further indicating that the quercetin-mediated inhibition of pyroptosis requires the participation of the Nrf2 pathway. In conclusion, quercetin promoted the nuclear translocation of Nrf2, increased the expression of antioxidant factors in cells, and inhibited the progression of cell pyroptosis, thereby alleviating diabetic cardiomyopathy.http://dx.doi.org/10.1155/2022/9723632 |
| spellingShingle | Zhang Wei Zhou Jing Kang Pinfang Shi Chao Qian Shaohuan Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway Journal of Diabetes Research |
| title | Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway |
| title_full | Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway |
| title_fullStr | Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway |
| title_full_unstemmed | Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway |
| title_short | Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway |
| title_sort | quercetin inhibits pyroptosis in diabetic cardiomyopathy through the nrf2 pathway |
| url | http://dx.doi.org/10.1155/2022/9723632 |
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