In vivo and in vitro insights into the anti-hyperuricemic effects of sacha inchi ( plukenetia volubilis l. ) leaves extract rich in polyphenols

Sacha inchi (SI, Plukenetia volubilis L.) is a South American oleaginous crop with multiple health benefits and has been traditionally used to treat various ailments due to its bioactive ingredients such as polyphenols and flavonoids. In this study, a variety of compounds including three flavonoids (epigallocatechin, luteolin-3 ' ,7-di-O- glucoside and cosmosiin), two polyphenols (gallic acid and 4-hydroxycoumarin) and three organic acids (malic acid, citric acid and 2-isopropylmalic acid) were firstly identified by UHPLC-QQQ-MS. Subsequently, in vitro results show that SI leaf aqueous extract (SILE) exhibit potential to lower uric acid (UA) by affecting mRNA levels of UA synthases (XO and HGPRT) with neglectable impacts on cell viability of liver cells (L02). In vivo experiments further suggest that SILE can effectively reduce the levels of serum UA and renal inflammatory cytokines ( Il-1 beta , Il-6 and Tnf- alpha ), and improve renal function indicators (serum Cr and BUN), thereby repairing kidney injury in both acute and chronic hyperuricemic (HUA) animal models. In addition, SILE also improve UA metabolism by inhibiting UA biosynthesis and reabsorption and promoting UA excretion. 1 H NMR-based metabolomics reveals that SILE effectively regulate the levels of glucose, amino acid, purine and pyrimidine that are involved in UA metabolic pathway in kidney of HUA mice. These findings demonstrate that SILE rich in polyphenols and flavonoids has a great potential for HUA treatment by inhibiting xanthine oxidase activity and improving UA metabolism.