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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. [ABSTRACT FROM AUTHOR]

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients. [ABSTRACT FROM AUTHOR]