Kaempferitrin attenuates unilateral ureteral obstruction‐induced renal inflammation and fibrosis in mice by inhibiting NOX4‐mediated tubular ferroptosis
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| Format: | Artículo Open Access |
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2024
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| _version_ | 1867016027714355200 |
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| author | Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang |
| author_facet | Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang |
| collection | Wiley Open Access |
| contents | Kaempferitrin attenuates unilateral ureteral obstruction‐induced renal inflammation and fibrosis in mice by inhibiting NOX4‐mediated tubular ferroptosis Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang Phytotherapy Research AbstractTubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti‐inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model‐induced renal inflammation and fibrosis. In vitro, erastin‐induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4‐hydroxynonenal (4‐HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin‐NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4‐mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD. 10.1002/ptr.8191 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8191 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8191 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Kaempferitrin attenuates unilateral ureteral obstruction‐induced renal inflammation and fibrosis in mice by inhibiting NOX4‐mediated tubular ferroptosis Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang Phytotherapy Research Kaempferitrin attenuates unilateral ureteral obstruction‐induced renal inflammation and fibrosis in mice by inhibiting NOX4‐mediated tubular ferroptosis Jianchun Li Jieke Yang Qianwen Xian Hongwei Su Yufang Ni Li Wang Phytotherapy Research AbstractTubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti‐inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model‐induced renal inflammation and fibrosis. In vitro, erastin‐induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4‐hydroxynonenal (4‐HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin‐NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4‐mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD. 10.1002/ptr.8191 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Kaempferitrin attenuates unilateral ureteral obstruction‐induced renal inflammation and fibrosis in mice by inhibiting NOX4‐mediated tubular ferroptosis |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8191 |