Protective effect of JBP485 on concanavalin A-induced liver injury in mice

Abstract

Objectives Cyclo-trans-4-L-hydroxyprolyl-L-serine (JBP485) was first isolated from Laennec (hydrolysate of human placenta). We thought it valuable to clarify the antihepatitis molecular mechanism of JBP485 to develop a new oral anti-hepatitis drug. Methods We investigated the hepatoprotective effect of JBP485 on immune-mediated, concanavalin A (Con A)-induced liver injury in mice. Mice were administered JBP485 before and after injection of Con A (10 mg/kg). Eight hours after Con A, the cytosolic enzyme activity (alanine aminotransferase, lactate dehydrogenase) in serum, and the enzyme activity or concentration (superoxide dismutase, maleic dialdehyde, myeloperoxidase, nitric oxide) in liver homogenate were determined. The liver slices were investigated to observe changes in histology. The effect of JBP485 on level of tumour necrosis factor-a (TNF-a) and intercellular adhesion molecule-1 (ICAM-1) in liver were detected by immunohistochemistry. Hepatocyte DNA fragmentation was assayed by agarose gel electrophoresis and the transcription of the genes bax and bcl-2 in hepatocytes was determined by reverse transcription-polymerase chain reaction. Key findings Con A increased the cytosolic and liver homogenate enzyme activity, and the concentrations of ICAM-1 and TNF-a, which were significantly inhibited by JBP485 administration. Also, the increase in DNA fragmentation and decrease in bcl-2/bax mRNA induced by Con A administration were significantly inhibited by JBP485. Conclusions These results indicated that immune-mediated liver damage can be prevented by JBP485, and that this is mainly associated with immunomodulatory effects on T cells and adhesion molecules, antioxidation, and inhibition of apoptosis.

Aspirin and Probenecid Inhibit Organic Anion Transporter 3–Mediated Renal Uptake of Cilostazol and Probenecid Induces Metabolism of Cilostazol in the Rat

“…7B). JBP485 is a dipeptide (Liu et al, 2000) with antihepatitis and gastrointestinal protective effects (Liu et al, 1998;Wu et al, 2008) that was first isolated from Laennec (Yang et al, 2009), a substrate of OAT1 and OAT3 (Zhang et al, 2010). We found that PCG, probenecid, JBP485, and aspirin inhibited the uptake of cilostazol in a concentration-dependent manner (Fig.…”

Anti-inflammatory Effect of JBP485 on Dextran Sulfate Sodium-induced Colitis in Mice

“…1) is a dipeptide first isolated from Laennec [6]. Laennec is a proprietary product made from the hydrolysate of human placenta [7]. JBP485 has been reported to have several biological properties.…”

“…JBP485 has been reported to have several biological properties. In concanavalin A (Con A)-induced liver injury mouse model, administration of JBP485 reduced hepatic damage, such as increases in tumor necrosis factor (TNF)-α and intercellular adhesion molecule-1 expression and apoptosis in the liver [7]. Also, administration of JBP485 to rats improved gentamicin-induced acute renal failure [8].…”

Simultaneous determination of three dipeptides (JBP485, Gly–Sar and JBP923) in the cell lysates by liquid chromatography‐tandem mass spectrometry: application to identify the function of the PEPT1 transfected cell

“…1C) are also dipeptides first isolated from Laennec, which are proprietary products made from the hydrolysate of human placenta in Japan, and have been synthesized by chemical means. Animal experiments have indicated that JBP485 and JBP923 could protect liver after oral administration of JBP485 and JBP923 (Liu et al, 1998(Liu et al, , 2000Sun et al, 2009;Terada et al, 1997;Wang et al, 2011aWang et al, , 2011bWu et al, 2008;Yang et al, 2009;Zhang et al, 2010).…”