Effect of N, N-Dimethylglycine on Homocysteine Metabolism in Rats Fed Folate-Sufficient and Folate-Deficient Diets.

OBJECTIVE: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. METHODS: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. RESULTS: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. CONCLUSION: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.

Pharmacokinetics and metabolism of icaritin in rats by UPLC-MS/MS.

Icaritin (ICT) has distinct bioactivities, especially known for its beneficial effects on bone-related degenerative disorders; however, its pharmacokinetic properties remain unknown. A novel developed UPLC-MS/MS method for the determination of ICT and its main metabolite glucuronidated icaritin (GICT) was firstly applied to pharmacokinetic and metabolism studies of ICT in female rats, which were intraperitoneally given 40 mg/kg ICT. Following the protein precipitation of plasma samples with acetonitrile, ICT and GICT were separated on a C18 column using gradient elution mode and quantified in the multiple reaction monitoring mode. The linearities were acceptable for ICT (r = 0.9960) and GICT (r = 0.9968), and the lower limit of quantification values was 0.5 and 5 ng/ml, respectively. The accuracy fell in the range of 92.0%-103.1% and precisions were within 9.5%. Good linearity, accuracy, precision, and recovery were achieved for the UPLC-MS/MS method. ICT was predominantly and rapidly biotransformed to GICT which was slowly eliminated in vivo with a terminal half-life value of 4.51 hr. Pharmacokinetics of pure ICT eliminated biotransformation interference of Epimedium extract and disclosed genuine pharmacokinetic manner of ICT, as well as firstly elucidated low concentration and bioavailability of ICT in rat plasma.