The pharmacokinetic profiles of mogrosides in T2DM rats.

Luohanguo (LHG) extract major contenting mogrosides, as a nonnutritive sweetener, has been reported to exert a hypoglycemic effect on diabetic patients and animals. As the pharmacokinetics and pharmacodynamics of drugs were changed with diabetes, it may lead to the different pharmacological of mogrosides between diabetic and normal subjects. To characterise the pharmacokinetic profiles of mogrosides in T2DM rats. High-fat diet and streptozocin induced type 2 diabetic mellitus rats were used to investigate the pharmacokinetic behavior of mogroside V and mogrosides IIIA 1 , IIA 1 , and IA 1 after T2DM rats orally administrated with mogroside V and 1–3 glucose residues' mogrosides, respectively. The validated convenient UPLC-QTOF/MS and UPLC-MS/MS methods were established to use in the pharmacokinetic studies of mogrosides in normal and T2DM rats. Additionally, the expression of the intestinal tight junction protein zonula occludens-1 (ZO-1) was also detected by immunohistochemical analysis, which assessed the function of passive intestinal permeability in T2DM rats. The results showed that for rats treated with mogroside V, its metabolite mogroside IIIA 1 has a significant increase (p < 0.05) in maximum plasma concentration (C max , 163.80 ± 25.56 ng/mL) and area under the plasma concentration (AUC 0-t , 2327.44 ± 474.63 h·ng/mL) in T2DM rats compared with in normal rats. The mean residence time (MRT 0-t , 12.04 ± 0.97 h) of mogroside V showed a significant decrease (p < 0.05) in T2DM rats. However, the mogrosides IIIA 1 , IIA 1 and IA 1 showed no statistical differences in the normal and T2DM rats after administered with 1–3 glucose residues' mogrosides. Furthermore, the expression level of ZO-1 in the duodenum and colon of T2DM rats were downregulated. The pharmacokinetic profiles of mogroside V and its metabolite mogroside IIIA 1 in T2DM rats and normal rats showed some difference, it might be affected by the metabolic changes in the pathological state of T2DM. [Display omitted] • The absorption behavior of mogroside V and its metabolite mogroside IIIA 1 were influenced by the T2DM condition in T2DM rats. • After administrated with mogrosides, the absorption of mogrosides IIIA1, IIA1 and IA1 showed no marked changes in T2DM rats. • The expression of ZO-1 protein in the T2DM rat's duodenum and colon were decreased. • It provides reference for understanding the pharmacokinetics and pharmacodynamics of mogrosides in both normal and T2DM rats. [ABSTRACT FROM AUTHOR]