Identification of a Hepatoprotective Peptide in Wheat Gluten Hydrolysate against d-Galactosamine-Induced Acute Hepatitis in Rats

Abstract

A hepatoprotective peptide, pyroglutamyl leucine (pyroGlu-Leu), was identified in wheat gluten hydrolysate through an in vivo activity-guided fractionation approach based on D-galactosamine-induced acute hepatitis in rats and fractionation of peptides with large-scale preparative ampholine-free isoelectric focusing. The active acidic fraction predominantly consisted of pyroglutamyl peptides and free pyroglutamic acid. Pyroglutamyl peptides were derivatized with phenyl isothiocyanate after removal of a pyroglutamyl residue by pyroglutamate aminopeptidase. The derivatives were purified by reversed-phase HPLC and subjected to sequence analysis. The active fraction contained pyroGlu-Ile, pyroGlu-Leu, pyroGlu-Gln, pyroGlu-Gln-Gln, and free pyroGlu. Ingestion of pyroGlu-Leu at 20 mg/kg body weight significantly decreased serum aspartate and alanine aminotransferases to approximately 30% and 20% of those values of the vehicle group, respectively, which were near the normal levels. Thirty minutes after ingestion of pyroGlu-Leu at 20 mg/kg, the concentration of pyroGlu-Leu in portal blood plasma increased to approximately 2 μM.

Anti-inflammatory effect of pyroglutamyl-leucine on lipopolysaccharide-stimulated RAW 264.7 macrophages

“…Our research group recently reported that pyroGlu-Leu suppressed D-galactosamine (D-GalN)-induced hepatitis in rats (Sato et al, 2013). We have also found that pyroGlu-Leu decreases plasma TNF-α and IL-6 levels in LPS-administered mice (unpublished data).…”

“…Higaki-Sato et al (2006) reported that significant amounts of free pyroglutamic peptides were observed in the portal veins of rats administered with WGH. Furthermore, Sato et al (2013) recently demonstrated that pyroglutamyl-leucine (pyroGlu-Leu) is the active component in WGH that exerts hepatoprotective activity. These results suggest that pyroglutamyl peptides, especially pyroGlu-Leu, may be the effective components that act on these inflammatory diseases; however, the underlying mechanism has not been clarified.…”

Beneficial effects of fermented sardinelle protein hydrolysates on hypercaloric diet induced hyperglycemia, oxidative stress and deterioration of kidney function in wistar rats

“…These findings were in agreement with the results previously reported by Ben Khaled et al (2012) who reported the potential hepatoprotective effect of sardinelle muscle hydrolysates (Sardinella aurita). In the same context, wheat gluten peptides have shown their protective effect against D-galactosamine induced a cute hepatits in rats (Sato et al 2013). …”

Antidepressant-like effect of food-derived pyroglutamyl peptides in mice

“…It has recently been revealed that YL also exhibits antidepressant-like activity (Mizushige, unpublished observation). We then investigated whether wheat-derived pyroglutamyl peptides, including pyroGlu-Leu (pEL, Sato et al, 2013) and pyroGlu-Gln-Leu (pEQL), with structural similarity to YL, exhibit antidepressant-like effects in mice.…”