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This study aimed to isolate and investigate the potential of the peptide alanine-cysteine-glutamic acid-cysteine-aspartic acid (ACECD), a novel xanthine oxidase inhibitory (XODI) peptide derived from Skipjack tuna hydrolysate (HS). Ultrafiltration membranes were used to obtain HS-based peptides as successive ultrafiltration fractions (of decreasing molecular weight) of UF-1, UF-2, UF-3, and UF-4. Their antioxidant and xanthine oxidase (XOD) inhibitory activities were determined and further characterized by affinity-ultrafiltration coupled with HPLC-MALDI-TOF/TOF-MS and in silico techniques. The results showed that peptides with a molecular weight (MW) cutoff of 600-1000 Da (UF-2) exhibited the highest antioxidant and XODI activities. A novel XODI peptide (ACECD) was identified with an IC 50 value of 13.40 mmol/L, which decreased by 21.24% and 51.40% compared to those of UF-2 and HS, respectively. Molecular docking indicated that ACECD inserted into the active center of Mo atoms in XOD, which led to competitive attachment with XOD and caused inhibition. The study findings indicated that the ACECD peptide could be useful as a safe XODI substance to alleviate hyperuricemia., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Propeptides of lipases have been demonstrated to influence many properties of their mature proteins as intramolecular chaperones. However, the working mechanism of propeptides may be different., Objectives: The main objective of this study was to determine the role of pentapeptide prosequence of Thermomyces lanuginosus lipase (TLL) through its effect on the recombinant expression of TLL in P. pastoris, and explore the possible function mechanism with its hydrophobicity., Methods: We have synthesized a codon-optimized TLL gene coTLL with a Kex2 cleavage site "- KREAEA-" directly after the propeptide "SPIRR-", and obtained expression vector pP-kTL through cloning it into pPIC9K. TL gene without the propeptide and pTL gene with a propeptide directed linked to mature TLL lipase, were also amplified and cloned into pPIC9K to obtain the expression vector pP-TL and pP-pTL. pTL-P and pTL-VP gene variants with mutation in pentapeptide prosequence of TLL were obtained used the site-directed mutation with the pP-pTL plasmid as the template. The recombinant proteins were expressed in P. pastoris GS115. Lipase activity was determined by a spectrophotometric method previously reported using para-nitrophenyl palmitate (pNPP) as the substrate and the thermostability of lipases of TLL was analyzed by incubating at different temperatures (70°C and 80°C) for 5h and molecular dynamics simulation., Results: The average lipase activity of recombinant strains GS-pTL reached 434.32 U/mL, higher than that of GS-TL 377.71 U/mL. The fermentation result of the recombinant strains with modified propeptide showed that the extracellular lipase activity of GS-pTL-VP variant reached 483.29 U/mL, increasing by 11.27% compared with that of GS-pTL (434.32 U/mL). Further analysis performed on the lipase stabilities with propeptide variants by molecular dynamics simulation showed that the RMSD of variant pTL-VP was similar to that of pTL., Conclusion: This study revealed that the propeptide "SPIRR-" sequence is beneficial for enhancing TLL expression. In addition, the function of TLL propeptide was identified to be related to its hydrophobicity, implying that propeptide might play a role in assisting the formation of the hydrophobic protein core and accelerate the protein folding process. This work inspired us to attach more emphasis on the propeptide of other lipases for improving their recombinant expression, structure folding and enzymatic properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A validated 3D pharmacophore model was generated for a series of ACE inhibitory peptides, which consisted of five features (two hydrophobic functions, two hydrogen bond acceptors, and a negative ionizable function). The built model was able to correctly predict the activity of known ACE inhibitors. The model was then used as query to search 3D databases of peptides. Three novel peptides (I, II and III) were synthesized and biologically evaluated in vitro. It appears that the in vitro activity of peptides I, II and III was consistent with their molecular modeling results. Our results provided confidence for the utility of the pharmacophore model to retrieve novel ACE inhibitory peptides with desired biological activity by virtual screening., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

As the population ages, the pursuit of extended lifespan and improved healthspan has gained significance. This study assessed the anti-aging properties of sea cucumber peptides derived from Acaudina leucoprocta (SCP) through microbiome and metabolome analyses in Drosophila melanogaster. Supplementation with 0.2%, 0.4%, 0.6%, and 0.8% of SCP significantly boosted the survival rate and extended the mean and median lifespans in both male and female flies. Among them, 0.6% SCP treatment extended the mean and median lifespans of male flies by 21.01% and 25.48 %, which showed the most prominent lifespan-prolonging effect. Moreover, SCP enhanced the healthspan of male flies by improving their climbing ability, intestinal barrier function, and memory performance. Additionally, SCP boosted the survival rate of flies subjected to oxidative, starvation, and heat stress, with no significant effect observed under cold stress conditions. The lifespan-extension effect of SCP remained unaffected by dietary restriction, but was partially inhibited when provided with antibiotic-supplemented food. SCP modulated microbiota with increased the abundance of Lactobacillus , Rhodococcus , and Propioniciclava and decreased Acetobacter , Achromobacter , Pedobacter , and norank_f_ Saprospiraceae, which closely related with lifespan-extension effect. Furthermore, SCP induced a metabolic profile in 30-day-old flies more akin to that of 3-day-old flies, impacted 13 significantly regulated metabolites associated with amino acid, nucleotide, and carbohydrate metabolisms. These findings highlight SCP intervention as a promising anti-aging strategy. [Display omitted] [ABSTRACT FROM AUTHOR]

Hepatoprotective peptides are potential therapeutic substances used for curing and protecting the liver from diseases. In addition to the nutrition value, evidence indicates that these peptides have a potential role in the body's physiological process. Despite wider practicability of these peptides, their molecular structures still need to be further elucidated, to analyze and better understand its mechanism of action. Their structural variations are mainly attributed to their ultimate processing of different hydrolysates. This study summarizes potential sources, production, structure, and sequence of hepatoprotective peptides, specifically emphasizing on their protective mechanism(s) against alcoholic- and non-alcoholic liver disease. This study also describes an interaction between intestinal microbiota and hepatoprotective peptides. Preliminary research indicated that treatment with bioactive peptide promotes the balance of gut microbiota (GM), mitigates liver inflammation in mice, reverses neutrophil phagocytosis in individuals with alcoholic cirrhosis, and improves liver enzyme levels in excessive drinkers. Besides, it describes hepatoprotective peptides mechanism of action on intestinal microbiota. This work intends to add knowledge in the field of peptides and their impact on hepatoprotection. [Display omitted] • Pointed out the main production of hepatoprotective peptides. • Focused on the sequences of hepatoprotective peptides. • Summarized the differences of hepatoprotective mechanism between NAFLD and ALD. • Reviewed the interaction of hepatoprotective peptides with intestinal flora. [ABSTRACT FROM AUTHOR]

Constipation is a common gastrointestinal problem. This study aimed to identify a combination of prebiotics and wheat peptides (WP) to promote intestinal peristalsis and explore the underlying mechanism. First, we screened four prebiotics (galacto-oligosaccharides (GOS), fructose oligosaccharides (FOS), inulin (IN), and resistant dextrin (RD)) using a zebrafish model and found that GOS was the most synergistic with WP. We then tested the GOS-WP combination in a mouse model of loperamide (Lop)-induced constipation and found that it significantly improved constipation symptoms. Specifically, GOS-WP shortened the first black stool time, increased the number of defecation particles, accelerated small intestinal propulsion rate, and increased fecal water content. GOS-WP also normalized the colonic water transport system by inhibiting colonic AQP4/8 expression. Additionally, GOS-WP reversed Lop-induced morphological damage in the ileum and colon, increased colonic barrier, and reduced inflammation in mice. Furthermore, 16S rRNA gene sequence analysis showed that GOS-WP reversed the gut microbiota structure changes induced by Lop. GOS-WP significantly increased butyric acid and decreased BCFA levels, indicating improved gut health. Our findings suggest that the GOS-WP combination has potential as a novel intervention for constipation relief. This study highlights the potential of combining prebiotics and WP as a therapeutic strategy for constipation. • Among GOS, FOS, IN and RD, GOS and WP had the strongest synergistic effect in promoting intestinal peristalsis. • The GOS to WP ratio of 1:2 was the most effective in promoting intestinal peristalsis in zebrafish model. • The GOS-WP complex (1:2) could relive constipation under mice model. • The GOS-WP complex (1:2) improved the disturbances of intestinal function in constipated mice. • The GOS-WP complex (1:2) recovered the gut microbiota composition in constipated mice. [ABSTRACT FROM AUTHOR]

Constipation has become more common in recent decades, affecting people's quality of life. Natural bioactive substances could be effective in alleviating constipation. The goal of this study was to assess and compare the efficacy of low and high hydrolysis degree wheat peptides (WP-L and WP-H) at a dose of 1 mg/g.bw on relieving loperamide-induced constipation in mice and the underlying mechanisms. Here, we proved that both WP-L and WP-H treatment showed constipation relieving effect by improving defecation function and small intestinal propulsion rate while the different hydrolysis degree did not affect the efficacy of WP. Moreover, WP-L and WP-H could balance the secretion of excitatory and inhibitory factors, and enhance the activity of antioxidant enzyme (SOD and GSH-Px). Importantly, both of them could accelerate intestinal motility, improve water-salt metabolism and intestinal barrier, and ameliorate oxidative stress. In summary, our findings indicated that 1 mg/g.bw WP-L and WP-H effectively relieved loperamide-induced constipation by affecting multiple targets in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

The potential of soft-shelled turtle peptides (STP) against fatigue was evaluated. Mice orally supplemented with STP significantly increased the swimming time until tiredness by 35.4–57.1%. Although not statistically significant, STP increased muscle and thymus mass. In addition, the serum lactate, ammonia, blood urea nitrogen content and creatine kinase activity in STP-fed mice were dramatically decreased when compared to the control group. Furthermore, STP supplementation increased the reserves of liver glycogen and muscle glycogen, thus improved the energy metabolism system of mice. STP treatment contributed to increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as a decrease in malondialdehyde (MDA), indicating an improvement in oxidative stress protection. The Western blot (WB) results indicated that the STP supplement effectively altered the expression of oxidative stress-related protein by modulating the NRF2/KEAP1 pathway. In summary, STP affected NRF2/KEAP1 levels in skeletal muscle, leading to antioxidant activity and a slower time to exhaustion during exercise. [ABSTRACT FROM AUTHOR]

The hydrolysate of silkworm protein produced by acid protease ( Asperqiius usamii NO. 537) contains angiotensin I-converting enzyme inhibitory activity. Four kinds of protein components were identified in silkworm pupae protein, albumin, globulin, prolamin and glutelin, and the albumin was in the highest quantity. The four component proteins were then further hydrolyzed by acid protease under the same conditions, and the hydrolysate of albumin was determined with the highest ACE inhibiting effect, followed by globulin. Albumin could be easily hydrolyzed under the aqueous conditions, and the overall albumin protein content was higher than the other three protein components. The peptide sequence 'APPPKK' was determined by LC-MS/MS separation and X!Tandem software identification. The peptide inhibitory activity was 0.047 mg/mL in IC. The peptide was bonded to Asp, Asp, Thr, His , Glu in hydrogen bond to ACE active pocket by flexible docking calculations. This study indicates that silkworm pupae protein may be a suitable candidate to explore functional foods with anti-hypertension bioactivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The anti-OA effect of Salmonidae bone collagen peptide (CP) was assessed. • CP was confirmed to inhibit the matrix degradation both in vitro and in vivo. • CP suppressed the role of pro-inflammatory via inhibiting NF-κB signal. • CP impeded the serious destruction of subchondral bone. • CP effectively prevent osteoarthritis in pMMx models as a dietary supplement. Nowadays, the biological activity of collagen peptides has been revealed, but the effect of Atlantic salmon (Salmo salar) bone-derived collagen peptide (CPs) on osteoarthritis remains unclear. In this study, CPs was identified as a small molecular weight peptide rich in Gly-X-Y structure. Meanwhile, interleukin-1β (IL-1β)-induced hypertrophic chondrocytes and partial medial meniscectomy (pMMx) surgery model in rats were performed. In IL-1β stimulated chondrocytes, CPs significantly increased the type-II collagen content, reduced the type-X collagen abundance and chondrocytes apoptosis. Meanwhile, CPs reversed the increased expression of matrix metalloproteinase, metalloproteinase with thrombospondin motifs and RUNX family transcription factor 2 in chondrocytes induced by IL-1β. In vivo , CPs increased pain tolerance of rats and without organ toxicity at 1.6 g/ kg.bw. CPs significantly decreased the levels of COMP and Helix-II in serum. Furthermore, a significant decrease of IL-1β in synovial fluid and cartilage tissue were observed by CPs intervention. From Micro-CT, CPs (0.8 g/ kg.bw) significantly decreased Tb.sp and SMI value. Meanwhile, the expression of tumor necrosis factor and interleukin-6 were reduced by CPs administration both in vitro and in vivo. Together, CPs showed potential to be a novel and safe dietary supplement for helping anti-inflammatory and cartilage regeneration, ultimately hindering osteoarthritis development. However, the clear mechanism of CPs's positive effect on osteoarthritis needs to be further explored. [ABSTRACT FROM AUTHOR]