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Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling.
Sun, Mingyang; Chang, He; Jiang, Fangyang; Zhang, Wenjing; Yang, Qingxuan; Wang, Xinhe; Lv, Guangfu; Lin, He; Luo, Haoming; Lin, Zhe; Wang, Yuchen.
Afiliação
  • Sun M; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Chang H; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Jiang F; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Zhang W; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Yang Q; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Wang X; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Lv G; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Lin H; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Luo H; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Lin Z; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
  • Wang Y; College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China.
Molecules ; 29(8)2024 Apr 11.
Article em En | MEDLINE | ID: mdl-38675549
ABSTRACT
Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP's actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP's nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / Transdução de Sinais / Cisplatino / Folhas de Planta / Injúria Renal Aguda / Polifenóis / Ferroptose / Via de Sinalização Hippo Limite: Animals / Humans / Male Idioma: En Revista: Molecules Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Extratos Vegetais / Transdução de Sinais / Cisplatino / Folhas de Planta / Injúria Renal Aguda / Polifenóis / Ferroptose / Via de Sinalização Hippo Limite: Animals / Humans / Male Idioma: En Revista: Molecules Ano de publicação: 2024 Tipo de documento: Article