Hypocholesterolemic Action of Eritadenine Is Mediated by a Modification of Hepatic Phospholipid Metabolism in Rats

Abstract

The hypocholesterolemic action of eritadenine, a compound found in the mushroom Lentinus edodes, was investigated in relation to its influence on phospholipid metabolism in the liver of rats fed diets containing different amounts of choline chloride (0, 2 and 8 g/kg diet). The time-dependent effect of eritadenine supplementation was also investigated. Eritadenine supplementation (50 mg/kg diet) significantly decreased the phosphatidylcholine (PC):phosphatidylethanolamine (PE) ratio in liver microsomes and the S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio in the liver, in addition to the plasma cholesterol concentration, irrespective of dietary choline levels. There was a significant correlation between the plasma cholesterol concentration and the liver microsomal PC:PE ratio. Although eritadenine caused fatty liver when added to the diets containing 0 or 2 g/kg choline chloride, a high level (8 g/kg) of choline chloride fully prevented the eritadenine-induced fatty liver without diminution of hypocholesterolemic action. Both the PC:PE ratio and the SAM:SAH ratio decreased significantly prior to the decrease in the plasma cholesterol concentration (1 d vs. 2 d after) in response to eritadenine supplementation, supporting the hypothesis that the alteration of hepatic phospholipid metabolism may be a cause of the hypocholesterolemic action of eritadenine. These observations suggest that the essential hypocholesterolemic action of eritadenine might be associated with a modification of hepatic phospholipid metabolism rather than with the PC deficiency, due to the inhibition of PE N-methylation.

Suppression of Methionine-Induced Hyperhomocysteinemia by Glycine and Serine in Rats

“…The concentrations of total homocysteine and cysteine in the plasma and liver were measured by HPLC according to the method of Durand et al 14) The concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the liver were measured by HPLC essentially according to the method of Cook et al 15) with slight modifications as described previously. 16) The activity of cystathionine -synthase (CBS) in the liver was measured according to the method of Mudd et al, 17) but using HPLC for the assay of the reaction product, cystathionine, according to the method of Einarsson et al 18) Protein was measured according to the method of Lowry et al, 19) using bovine serum albumin as the standard.…”

Mushrooms as therapeutic agents

“…Eritadenine affects the metabolism not only of cholesterol but also of phospholipids and fatty acids in rats (Suzuki & Ohshima, 1976;Sugiyama et al, 1995). The dietary supplementation of eritadenine may therefore decrease phosphatidylcholine biosynthesis by altering the phosphatidylethanolamine concentration (Shimada et al, 2003).…”

“…In addition to eritadenine, nucleic acid compounds extracted from L. edodes were found to be inhibitors of platelet agglutination (Sugiyama et al, 1995). Lovastatin and its analogues are powerful inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and as such are well-known cholesterol-lowering agents (Shimada et al, 2003).…”

High Casein Diet Decreases Plasma Homocysteine Concentration in Rats

“…The plasma protein-bound homocysteine concentration was estimated by subtracting the non-protein-bound homocysteine from the total homocysteine. The concentrations of S -adenosylmethionine (SAM) and S -adenosylhomocysteine (SAH) in the liver were measured by HPLC essentially according to the method of Cook et al ( 22 ) with slight modifications as described previously ( 23 ). The concentration of betaine in the liver was measured by HPLC according to the method of Laryea et al ( 24 ) and the concentration of serine in the liver was measured by an amino acid autoanalyzer.…”