Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease
Background: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert prot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2093 |
| _version_ | 1827647465396895744 |
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| author | Hengli Zhao Gaopeng Xian Jingxin Zeng Guoheng Zhong Dongqi An You Peng Dongtu Hu Yingwen Lin Juncong Li Shuwen Su Yunshan Ning Dingli Xu Qingchun Zeng |
| author_facet | Hengli Zhao Gaopeng Xian Jingxin Zeng Guoheng Zhong Dongqi An You Peng Dongtu Hu Yingwen Lin Juncong Li Shuwen Su Yunshan Ning Dingli Xu Qingchun Zeng |
| author_sort | Hengli Zhao |
| collection | DOAJ |
| description | Background: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert protective effects in multiple diseases. However, the role of hesperetin in CAVD remains unclear. Methods: Human aortic valve interstitial cells (VICs) were isolated from aortic valve leaflets. A mouse model of aortic valve stenosis was constructed by direct wire injury (DWI). Immunoblotting, immunofluorescence staining, and flow cytometry were used to investigate the roles of sirtuin 7 (Sirt7) and nuclear factor erythroid 2-related factor 2 (Nrf2) in hesperetin-mediated protective effects in VICs. Results: Hesperetin supplementation protected the mice from wire-injury-induced aortic valve stenosis; in vitro, hesperetin inhibited the lipopolysaccharide (LPS)-induced activation of NF-κB inflammatory cytokine secretion and osteogenic factors expression, reduced ROS production and apoptosis, and abrogated LPS-mediated injury to the mitochondrial membrane potential and the decline in the antioxidant levels in VICs. These benefits of hesperetin may have been obtained by activating Nrf2–ARE signaling, which corrected the dysfunctional mitochondria. Furthermore, we found that hesperetin could directly bind to Sirt7 and that the silencing of Sirt7 decreased the effects of hesperetin in VICs and potently abolished the ability of hesperetin to increase Nrf2 transcriptional activation. Conclusions: Our work demonstrates that hesperetin plays protective roles in the aortic valve through the Sirt7–Nrf2–ARE axis; thus, hesperetin might be a potential dietary supplement that could prevent the development of CAVD. |
| first_indexed | 2024-03-09T19:19:28Z |
| format | Article |
| id | doaj.art-dfe433cd7d9f4ca1b5ad66d99802e293 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:19:28Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-dfe433cd7d9f4ca1b5ad66d99802e2932023-11-24T03:29:06ZengMDPI AGAntioxidants2076-39212022-10-011111209310.3390/antiox11112093Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve DiseaseHengli Zhao0Gaopeng Xian1Jingxin Zeng2Guoheng Zhong3Dongqi An4You Peng5Dongtu Hu6Yingwen Lin7Juncong Li8Shuwen Su9Yunshan Ning10Dingli Xu11Qingchun Zeng12State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaSchool of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaState Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaBackground: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert protective effects in multiple diseases. However, the role of hesperetin in CAVD remains unclear. Methods: Human aortic valve interstitial cells (VICs) were isolated from aortic valve leaflets. A mouse model of aortic valve stenosis was constructed by direct wire injury (DWI). Immunoblotting, immunofluorescence staining, and flow cytometry were used to investigate the roles of sirtuin 7 (Sirt7) and nuclear factor erythroid 2-related factor 2 (Nrf2) in hesperetin-mediated protective effects in VICs. Results: Hesperetin supplementation protected the mice from wire-injury-induced aortic valve stenosis; in vitro, hesperetin inhibited the lipopolysaccharide (LPS)-induced activation of NF-κB inflammatory cytokine secretion and osteogenic factors expression, reduced ROS production and apoptosis, and abrogated LPS-mediated injury to the mitochondrial membrane potential and the decline in the antioxidant levels in VICs. These benefits of hesperetin may have been obtained by activating Nrf2–ARE signaling, which corrected the dysfunctional mitochondria. Furthermore, we found that hesperetin could directly bind to Sirt7 and that the silencing of Sirt7 decreased the effects of hesperetin in VICs and potently abolished the ability of hesperetin to increase Nrf2 transcriptional activation. Conclusions: Our work demonstrates that hesperetin plays protective roles in the aortic valve through the Sirt7–Nrf2–ARE axis; thus, hesperetin might be a potential dietary supplement that could prevent the development of CAVD.https://www.mdpi.com/2076-3921/11/11/2093hesperetincalcified aortic valve diseaseSirt7Nrf2 |
| spellingShingle | Hengli Zhao Gaopeng Xian Jingxin Zeng Guoheng Zhong Dongqi An You Peng Dongtu Hu Yingwen Lin Juncong Li Shuwen Su Yunshan Ning Dingli Xu Qingchun Zeng Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease Antioxidants hesperetin calcified aortic valve disease Sirt7 Nrf2 |
| title | Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease |
| title_full | Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease |
| title_fullStr | Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease |
| title_full_unstemmed | Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease |
| title_short | Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease |
| title_sort | hesperetin a promising dietary supplement for preventing the development of calcific aortic valve disease |
| topic | hesperetin calcified aortic valve disease Sirt7 Nrf2 |
| url | https://www.mdpi.com/2076-3921/11/11/2093 |
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