Tyr-Leu-Asp-Asn-Tyr (YLDNY) is an orally active antihyperuricemic peptide. However, its metabolic fate after oral administration and mechanism of action remain unclear. YLDNY resisted pepsin digestion, and intact YLDNY, with smaller amounts of peptide fragments, remained in the stomach after administration to rats. In contrast, YLDNY was completely degraded by exopeptidase digestion and was not detected in the luminal contents of the anterior parts of the small intestine. Only a small quantity of tetrapeptide (Tyr-Leu-Asp-Asn (YLDN)) was detected in the luminal contents of the anterior parts of the small intestine, although there was no significant increase after administration. None of the intact or modified peptides increased in portal and abdominal bloods, stomach and liver extracts. However, hepatic xanthine levels increased significantly 2 h after YLDNY administration compared to amino acid mixture administration, suggesting hepatic xanthine oxidase activity suppression. This discrepancy implies the involvement of an alternative mechanism of stomach or gut-liver signaling.

This study identified peptides in fish and soy sauces and elucidated their bioavailability in rats. Over 96 peptides including γ-glutamyl, pyroglutamyl, β-aspartyl peptides, and diketopiperazines were detected. The content of these peptides varied greatly between the products tested. After the administration of Vietnamese fish sauce which had the highest peptide content among samples tested, most normal peptides did not significantly increase in the blood; whereas γ-glutamyl and pyroglutamyl peptides significantly increased in the small intestine and some hydrophobic γ-glutamyl isopeptides and pyroglutamyl-proline significantly increased in the blood. Diketopiperazines and β-aspartyl isopeptides significantly increased in the small intestine and the blood. These findings highlight the presence of modified peptides in fish and soy sauces, which are commonly consumed in daily dishes in East Asia. Only modified peptides such as diketopiperazines, β-aspartyl isopeptides and hydrophobic γ-glutamyl isopeptides survived gastrointestinal digestion, entering blood circulation, suggesting their potential biological activities.

Gly-Pro-Hyp-Gly is the most common motif in collagen. Ingestion of collagen hydrolysate (CH) has been reported to significantly increase Pro-Hyp and Hyp-Gly in human peripheral blood. However, the elevation of Gly-Pro content remains negligible. This study seeks to elucidate the underlying reasons behind the bioavailability of CH-derived peptides using in vivo and in vitro digestion. After oral administration of CH (800 mg/kg body weight) to rats, Pro-Hyp significantly increased in the lumen, small intestinal tissue, and blood from the abdominal vein, while only negligible amounts of Gly-Pro were detected. In vitro digestion of CH by digestive exopeptidases, including aminopeptidase N, leucine aminopeptidase, and carboxypeptidase A predominantly generated Gly-Pro. Interestingly, the digestion of CH with crude extract of small intestinal mucosa predominantly generated Pro-Hyp and negligible amounts of Gly-Pro. Furthermore, synthetic Gly-Pro was rapidly degraded by crude extract of the intestinal mucosa, while Pro-Hyp showed higher resistance. These facts indicate prolidase activity in the mucosa plays a crucial role in determining collagen-derived peptides in the body.

Fermented sour soup is a traditional condiment in daily southwestern Chinese cuisine. Compounds found in Hong Yao sour soup were fractionated using size-exclusion chromatography. Amino compounds were identified through derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and liquid chromatography tandem mass-spectrometry (LC-MS/MS) with precursor scan, followed by identification using product ion scan. Other compounds lacking amino groups were isolated using solid-phase extraction with a strong cation exchanger and detected through LC-MS in full scan mode. Carbonyl compounds, including carboxylic acids, were detected and identified by derivatization with 2-nitrophenylhydrazine and LC-MS/MS. Besides amino acids and carboxylic acids including lactic and acetic acid, amino acid metabolites such as monoamines (tyramine, pyrrolidine, tryptamine), polyamines (cadaverine, putrescine), N-acetyl- and N-lacoyl-amino acids, and α-keto acids from Val, Ile, and Leu were also detected. However, unlike Japanese rice wine, only a few dipeptides were detected. This information aids in understanding the unique characteristics of Hong Yao sour soup.

The objective of this study was to elucidate the metabolic fate of peptides in a rice protein hydrolysate (RPH) in rats. Peptides present in RPH and its in vitro exopeptidase digest were identified using liquid chromatography-tandem mass spectrometry. One hour after an oral administration of RPH (250 mg/kg body weight), the levels of in vitro exopeptidase-resistant pyroglutamyl peptides in the lumen and ileal tissue significantly increased, whereas those of exopeptidase-susceptible peptides remained unchanged. Among them, the concentrations of pyroGlu-Leu, pyroGlu-Val, and pyroGlu-Lys significantly yet slightly increased in portal blood, while those of other hydrophilic ones (pyroGlu-Gln, pyroGlu-Glu, etc.) remained unchanged. However, all of the pyroglutamyl peptides were stable in rat ileal extract and blood plasma. These findings indicate that the pyroglutamyl peptides can enter enterocytes and resist to peptidases, while small amounts are transported to the blood, suggesting that pyroglutamyl peptides in enterocytes might be returned to the lumen.

Oral administration of food protein hydrolysate and naturally occurring peptides exert beneficial effects beyond conventional nutritional functions by supplying amino acids for protein synthesis. These peptides are referred to as food-derived bioactive peptides. The coronavirus disease 2019 (COVID-19) is caused by sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some host and viral proteins are involved in the entry of SARS-CoV-2 into cells and their replication. Peptides with specific sequences can interact with these proteins and have potential prophylactic and therapeutic activities against COVID-19. However, it is difficult to deliver food-derived peptides to target organs without degradation by exopeptidases in the body. Alternatively, food-derived peptides and amino acid metabolites have been suggested to decrease risk factors of COVID-19 by modulating the reninangiotensin system, the innate immune system, and the antioxidant system. This mini-review is based on in vivo responses to food-derived peptides and aims to introduce potential targets for these peptides in decreasing the risk and severity of COVID-19.

Miso, a paste of salted fermented soybean, is a seasoning used extensively in traditional Japanese cuisine. Herein, pyroglutamyl peptides present in miso were identified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS), detecting precursor ions, which generated immonium ion of pyroglutamyl residue. By using this method, 13 pyroglutamyl peptides were identified in four types of miso. Administration of the water extract prepared from 0.6 g soybean miso/kg body weight/day significantly suppressed high fat diet-induced weight gain. A similar effect was exerted by the hydrophobic pyroglutamyl peptide fraction, including pyroglutamyl proline (pEP), pEV, pEI, and pEL. Administration of a mixture of synthetic pEP, pEV, pEI, and pEL in a ratio to that in miso or pEL alone also suppressed the weight gain in a dose dependent manner. These results suggest that the short-chain hydrophobic pyroglutamyl peptides present in miso are effective in suppressing high fat diet-induced obesity.