The pharmacokinetic profiles of mogrosides in T2DM rats

Ethnopharmacological relevance: 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. Aims of the study: To characterise the pharmacokinetic profiles of mogrosides in T2DM rats. Study design and methods: High-fat diet and streptozocin induced type 2 diabetic mellitus rats were used to investigate the pharmacokinetic behavior of mogroside V and mogrosides IIIA1, IIA1, and IA1 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. Results: The results showed that for rats treated with mogroside V, its metabolite mogroside IIIA1 has a significant increase (p < 0.05) in maximum plasma concentration (Cmax, 163.80 +/- 25.56 ng/mL) and area under the plasma concentration (AUC0-t, 2327.44 +/- 474.63 h.ng/mL) in T2DM rats compared with in normal rats. The mean residence time (MRT0-t, 12.04 +/- 0.97 h) of mogroside V showed a significant decrease (p < 0.05) in T2DM rats. However, the mogrosides IIIA1, IIA1and IA1 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. Conclusion: The pharmacokinetic profiles of mogroside V and its metabolite mogroside IIIA1 in T2DM rats and normal rats showed some difference, it might be affected by the metabolic changes in the pathological state of T2DM.

Automated summary

This study aimed to characterize the pharmacokinetic profiles of mogrosides in T2DM rats. The results showed that there were significant differences in the pharmacokinetic parameters of mogroside V and its metabolite mogroside IIIA1 between T2DM rats and normal rats, possibly due to metabolic changes in the pathological state of T2DM.