Hypoglycemic action of semipurified fractions from hot-water extracts of the submerged-culture broth of Agaricus blazei Murill was examined in streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic male Sprague-Dawley rats, relative to the diabetes drug metformin. The hot-water extract, treated with ethanol to remove beta-glucans and glycoproteins, was freeze-dried, and fractionated into hexane, chloroform, ethyl acetate (EA), and butanol fractions. The EA fraction (EAF; 200 mg/kg body weight) reduced (p < 0.05) the blood glucose level in the oral glucose tolerance test, relative to the other fractions and control. In a 14 day-treatment study, diabetic rats treated with the EAF displayed a suppressed blood glucose level and elevated plasma insulin and glucose transport-4 proteins; the reactions occurred in a dose-dependent manner (200 and 400 mg/kg body weight) compared to those in control animals. The EAF reduced the levels of triglyceride and cholesterol in plasma, the activity of glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase in blood, and the content of thiobarbituric acid reactive substance in the liver and kidney. The hypoglycemic efficacy of the EAF (400 mg/kg body weight) was similar to that of metformin (500 mg/kg body weight). The EAF contained substantial amounts of isoflavonoids including genistein, genistin, daidzein, and daidzin, which could have contributed to the fraction's hypoglycemic action. These results indicate that the hot-water extract of the submerged-culture broth of Agaricus blazei contains an EAF having potent hypoglycemic action, which could be useful in the treatment of diabetes mellitus.

The influence of conjugated linoleic acid (CLA) on the growth of some foodborne and pathogenic bacteria was examined. A potassium salt of CLA (CLA-K) was tested against three Gram-positive strains ( Bacillus cereus , Staphylococcus aureus , and Streptococcus mutans ) and five Gram-negative strains ( Pseudomonas aeruginosa , Salmonella typhimurium , Vibrio parahemolyticus , Klebsiella pneumoniae , and Proteus mirabilis ). CLA-K-mediated growth inhibition was evident for all tested strains, particularly the Gram-positive strains. The IC(50) value of CLA-K was 0.3 mM for B. cereus, 1.2 mM for S. aureus, and 0.3 mM for S. mutans, whereas the value was 1.2 mM for K. pneumoniae, 1.2 mM for P. aeruginosa, 1.8 mM for S. typhimurium, 1.8 mM for V. parahemolyticus, and 2.4 mM for P. mirabilis. The CLA-K delayed the growth of all the tested strains at lower CLA-K concentrations, but completely inhibited the growth at higher concentrations. All cells grown in the medium containing CLA-K contained CLA in their membranes and exhibited irregular cell surface and cell disruption, which were greater in Gram-positive than Gram-negative strains. Higher lactic dehydrogenase activity (LDH), protein content, and malondialdehyde (MDA) content were evident in Gram-positive strains than in Gram-negative strains. These results suggest that the broad spectrum of growth inhibition by CLA mediated through the lipid peroxidation of CLA in the membranes and in the medium.

The differential anticarcinogenic activity of conjugated linoleic acid (CLA) isomers, including c9,t11-CLA, t10,c12-CLA, and t,t-CLA, was examined in a mouse forestomach carcinogenesis regimen induced by benzo(a)pyrene (BP). Female ICR mice (6-7 weeks of age, 26 +/- 1 g) were divided into six groups (30 mice/group, 5 mice/cage): control, linoleic acid, CLA, c9,t11-CLA, t10,c12-CLA, and t,t-CLA. Each mouse was orally given 0.1 mL of sample and 0.1 mL of olive oil on Monday and Wednesday and BP (2 mg in 0.2 mL of olive oil) on Friday. This cycle was repeated four times. Twenty-three weeks later, the experiment was terminated for tumor analysis. t,t-CLA significantly reduced (p < 0.05) both tumor number and tumor size per mouse, relative to CLA and c9,t11-CLA, but similar to t10,c12-CLA. Reduction in tumor incidence by t,t-CLA (84.6%) was similar to that by CLA, c9,t11-CLA, and t10,c12-CLA, but it was significantly reduced (p < 0.05), relative to 100% linoleic acid and control. t,t-CLA elevated the apoptotic index to 35%, relative to 23% for CLA, 21% for c9,t11-CLA, 29% for t10,c12-CLA, 7% for linoleic acid, and 4% for control. t,t-CLA up-regulated the expression of the Bax gene and activated caspase-3 enzymes but down-regulated expression of the Bcl-2 gene. Cytosolic phospholipase A(2) activity was not affected by the CLA isomers tested. These results suggest that t,t-CLA has superior anticarcinogenic potential on BP-induced mouse forestomach neoplasia to CLA, c9,t11-CLA, and t10,c12-CLA, via the induction of apoptosis through mitochondrial dysfunction.

No abstract