This study identified three novel anti-inflammatory peptides from sea cucumber gonad hydrolysates: GDRGF, FDGPEGPRGPPGSEGRQG, and PSNLGTGLR. In vitro experiments demonstrated that these peptides, at concentrations ranging from 25 to 400 μg/mL, exhibited no cytotoxicity toward RAW264.7 macrophages and significantly promoted cell proliferation (P < 0.05). In an lipopolysaccharide (LPS)-induced inflammation model, all three peptides markedly suppressed the secretion of nitric oxide (NO) and pro-inflammatory cytokines (P < 0.05), with GDRGF exhibiting the highest NO inhibition rate of 62.89%. Molecular docking results confirmed that the three peptides interact with Toll-like receptors 2 and 4 receptors via hydrogen bonding and hydrophobic interactions. Analysis of key residues suggested that internal or C-terminal arginine (R) may enhance anti-inflammatory activity by inhibiting NO production and blocking LPS signaling pathways. This study provides an efficient screening strategy for marine-derived anti-inflammatory peptides and lays a theoretical foundation for developing anti-inflammatory functional foods from sea cucumber gonads.

The gonad is one of the major byproducts of sea cucumber. Four novel antioxidant peptides (NPWGQ, PGHPF, VPYPR and ATGPQGPAGQRGPAGPTGPTGPAG) were isolated and identified from sea cucumber gonad proteins through enzymatic hydrolysis and antioxidant activity-guided fractionation, bioinformatics approaches and in silico screening. These peptides demonstrated great free radical (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS))-scavenging activity and notable superoxide dismutase (SOD)-activation capacity. Molecular docking and molecular dynamics simulation data suggested that these peptides could form strong binding with SOD through hydrogen bonding, electrostatic interactions, and hydrophobic interactions. Among these peptides, NPWGQ displayed the most potent antioxidant and SOD-activating effects. Through searching known databases, these peptides did not show potential toxicity and are generally considered safe. The present study provides crucial theoretical support for comprehensively utilizing sea cucumber (Holothuroidea) gonad by-products and generating high-value functional food ingredients or dietary supplements.

Long-term excessive intake of alcohol can cause serious damage to the liver, and the study of natural active ingredients with hepatoprotective effects is of great significance for the prevention and treatment of alcoholic liver injury. This study explored the ameliorative effects of high F-value oligopeptides (HFOPs) from Chlamys farreri, Pueraria lobata extract (PL), and their complex (HFOPs + PL) on alcoholic liver injury. Results showed HFOPs + PL significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage, increased superoxide dismutase (SOD) and glutathione (GSH) activities, and decreased the production of malondialdehyde (MDA) and inflammatory factors in alcohol-induced HepG2 cells. In mice, it prolonged intoxication time, shortened detoxification time, enhanced hepatic ADH and aldehyde dehydrogenase (ALDH) activities, reduced serum AST and ALT levels, and improved antioxidant capacity. Its effects were better than PL alone and comparable to HFOPs alone. HFOPs and PL alleviate alcoholic liver injury by enhancing ethanol metabolism, reducing oxidative stress, and suppressing inflammation, providing theoretical support for their combined use in alcohol detoxification and liver protection.