Sacha Inchi Oil Press-Cake Protein Hydrolysates Exhibit Anti-Hyperuricemic Activity via Attenuating Renal Damage and Regulating Gut Microbiota

The incidence of hyperuricemia has increased globally due to changes in dietary habits. The sacha inchi oil press-cake is generally discarded, resulting in the waste of resources and adverse environmental impact. For the purpose of developing sacha inchi oil press-cake and identifying natural components with anti-hyperuricemic activities, we systemically investigated the underlying mechanisms of sacha inchi oil press-cake protein hydrolysates (SISH) in the hyperuricemic rat model. SISH was obtained from sacha inchi oil press-cake proteins after trypsin treatment, and 24 peptides with small molecular weight (<1000 Da) were identified. The results of animal experiments showed that SISH significantly decreased the serum uric acid (UA) level by inhibiting the xanthine oxidase (XOD) activity and regulating the gene expression related to UA production and catabolism in hyperuricemia rats, such as Xdh and Hsh. In addition, SISH attenuated the renal damage and reduced the gene expression related to inflammation (Tlr4, Map3k8, Pik3cg, Pik3ap1, Ikbke, and Nlrp3), especially Tlr4, which has been considered a receptor of UA. Notably, SISH reversed high purine-induced gut microbiota dysbiosis, particularly by enhancing the relative abundance of butyric acid-producing bacteria (unidentified_Ruminococcaceae, Oscillibacter, , Ruminiclostridium, Intestinimonas). This research provided new insights into the treatment of hyperuricemia.