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Molecules ; 29(8)2024 Apr 11.
Article in English | 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.


Subject(s)
Acute Kidney Injury , Cisplatin , Ferroptosis , Hippo Signaling Pathway , Plant Extracts , Plant Leaves , Polyphenols , Signal Transduction , Animals , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Acute Kidney Injury/chemically induced , Ferroptosis/drug effects , Cisplatin/adverse effects , Polyphenols/pharmacology , Polyphenols/chemistry , Mice , Plant Extracts/pharmacology , Plant Extracts/chemistry , Humans , Signal Transduction/drug effects , Plant Leaves/chemistry , Protein Serine-Threonine Kinases/metabolism , Male , Cell Line , Antioxidants/pharmacology , Apoptosis/drug effects , Disease Models, Animal , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Oxidative Stress/drug effects
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