Hyperuricemia, a metabolic disorder related to uric acid metabolism dysregulation, has become a common metabolic disease worldwide, due to changes in lifestyle and dietary structure. In recent years, owing to their high activity and few adverse effects, food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention. This article aims to focus on the challenge associated with peptide-specific preparation methods development, functional components identification, action mechanism(s) clarification, and bioavailability improvement. The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting, increased the knowledge about strategies to search antihyperuricemia peptides with definite structure, and emphasized the necessity of combining computer-aided approaches and activity evaluations. In addition, novel action mechanism mediated by gut microbiota was discussed, providing different insights from classical mechanism. Moreover, considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides, we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships, which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement. Hopefully, this article could promote the development, application and commercialization of food-derived anti-hyperuricemia peptides in the future.

Marine fauna provides a plentiful repository of peptides and bioactive proteins. Peptides and proteins isolated from marine animals have been studied and applied in the development of food supplements, drugs, and cosmeceutical products because of their special bioactivities, such as anti-inflammatory and antioxidant effects This study focused on exploring the alleviating effects of five major marine animal-derived peptides (Apostichopus japonicus, Acaudina leucoprocta, Melanogrammus aeglefinus, Phascolosoma esculenta and Rhopilema esculentum) on adjuvant-induced arthritis (AIA). The treatment with five marine animals-derived peptides downregulated the expression levels of pro-inflammatory cytokines of IL-1β, IL-17 and TNF-α in the bones of the mice with AIA and alleviated the rough surface of bone tissues significantly. A. japonicus-treatment ameliorates inflammation by restoring NF-κB pathway in AIA mice. High-throughput sequencing of the gut microbiota based on 16S rRNA sequencing revealed that A. japonicus peptide-treated AIA mice showed alterations and imbalance of intestinal flora and an increased abundance of Lactobacillus and Clostridium. Furthermore, metabolomic analysis showed that the level of SCFAs in the feces was enhanced to different degrees in mice treated with five major marine animal-derived peptides. Taken together, we propose that major marine animal-derived peptides can alleviate arthritis by improving the imbalance in the gut flora and increasing SCFA production to varying degrees.

Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods, contributing to rising rates of hyperuricemia. The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide (GPSGRP) derived from sea cucumber in fructose induced hyperuricemia mouse model, and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites. Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice. In addition, treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level, Muribaculum, Prevotella and Bacteroides at the genus level, and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism. Moreover, serum metabolites, including linoleic acid, indole and its derivatives, arachidonic acid and uridine, as well as related metabolic pathways, such as tricarboxylic acid cycle, ketone production and sugar production, were altered in response to GPSGRP treatment. This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.

Ulcerative colitis (UC) is a recurrent inflammatory bowel disease that imposes a severe burden on families and society. In recent years, exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest. This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV (Pro-Lys-Lys-Val-Val) of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome. Specif ically, the polypeptide composition of R. esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α (TNF-α) than the original ligand. Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC; affect serum metabolites through the arachidonic acid, glycerophospholipid and linoleic acid metabolism pathways; and further alleviate UC symptoms. This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

Ultraviolet B (UVB)-induced cell death causes skin photoaging. In this study, we investigated the protective effect of Melanogrammus aeglefinus skin oligopeptide (MSOP) in UVB-irradiated human keratinocytes. The method of preparing MSOP was optimized, and three peptides with high abundance, VADML (Val-Ala-Asp-Met-Leu), IARF (Ile-Ala-Arg-Phe) and SSPSF (Ser-Ser-Pro-Ser-Phe), were identified. Discovery Studio predicted that these peptides interacted with Keap1 and contributed to antioxidant activity. Therefore, a UVB-induced cell model was used to explore the beneficial effects of MSOP in vitro. The activities of superoxide dismutase and glutathione peroxidase were increased in the MSOP-treated groups, while the malondialdehyde content was decreased. In addition, 23 differentially expressed proteins were identified through quantitative proteomics analysis; among them, the upregulation of Nrf2 and downregulation of Keap1, which are involved in the Keap1/Nrf2/ARE signaling pathway, contributed to the antioxidant process. Based on this study, MSOP might be an alternative agent for protecting the skin against UVB exposure.