Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3
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| Formato: | Artículo Open Access |
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Wiley
2024
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| _version_ | 1867009569912258560 |
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| author | Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li |
| author_facet | Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li |
| collection | Wiley Open Access |
| contents | Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3 Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li Phytotherapy Research AbstractHesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis‐related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing. 10.1002/ptr.8121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8121 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8121 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3 Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li Phytotherapy Research Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3 Xianbin Yu Zhixuan Liu Yitian Yu Chengjie Qian Yuzhe Lin Shuqing Jin Long Wu Shi Li Phytotherapy Research AbstractHesperetin (HST) is a flavonoid compound naturally occurring in citrus fruits and is widespread in various traditional medicinal herbs such as grapefruit peel, orange peel, and tangerine peel. These plant materials are commonly used in traditional Chinese medicine to prepare herbal remedies. The study aimed to investigate the potential molecular mechanisms through which HST reduces ferroptosis in human umbilical vein endothelial cells (HUVECs) and promotes angiogenesis and wound healing. We employed network pharmacology to predict the downstream targets affected by HST. The expression of markers related to ferroptosis was assessed through Western blot (WB) and polymerase chain reaction. Intracellular levels of ferroptosis‐related metabolism were examined using glutathione/oxidized glutathione (GSH/GSSG) and malondialdehyde (MDA) assay kits. Mitochondrial status and iron levels within the cells were investigated through staining with Mitosox, FerroOrange, and JC1 staining. Potential downstream direct targets of HST were identified using molecular docking. Additionally, wound healing and neovascularization within the wound site were analyzed using various methods including HE staining, Masson's staining, immunohistochemistry, and Doppler hemodynamics assessment. HST effectively inhibits the elevated levels of intracellular ferroptosis stimulated by ERASTIN. Furthermore, we observed that HST achieves this inhibition of ferroptosis by activating SIRT3. In a diabetic rat wound model, HST significantly promotes wound healing, reducing levels of tissue ferroptosis, consistent with our in vitro findings. This study demonstrates that HST can inhibit the progression of ferroptosis and protect the physiological function of HUVECs by activating SIRT3. HST holds promise as a natural compound for promoting diabetic wound healing. 10.1002/ptr.8121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Hesperetin promotes diabetic wound healing by inhibiting ferroptosis through the activation of SIRT3 |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8121 |