The pharmacokinetic profiles of mogrosides in T2DM rats

Yulong Zhang; Ying Peng; Guisheng Zhou; Xiaobo Li

doi:10.1016/j.jep.2021.114639

The pharmacokinetic profiles of mogrosides in T2DM rats

J Ethnopharmacol. 2022 Jan 10:282:114639. doi: 10.1016/j.jep.2021.114639. Epub 2021 Sep 14.

Authors

Yulong Zhang¹, Ying Peng¹, Guisheng Zhou¹, Xiaobo Li²

Affiliations

¹ School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China.
² School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, China. Electronic address: xbli@sjtu.edu.cn.

PMID: 34530093
DOI: 10.1016/j.jep.2021.114639

Abstract

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 (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 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.

Keywords: Intestinal permeability; Mogroside IIIA(1); Mogroside V; Pharmacokinetics; Zonula occludens-1.

MeSH terms

Animals
Area Under Curve
Chromatography, Liquid / methods
Diabetes Mellitus, Type 2 / chemically induced*
Diabetes Mellitus, Type 2 / metabolism*
Diet, High-Fat / adverse effects*
Gene Expression Regulation / drug effects
Glucosides / blood
Glucosides / pharmacokinetics*
Male
Mass Spectrometry / methods
Phytotherapy
Random Allocation
Rats
Rats, Sprague-Dawley
Triterpenes / blood
Triterpenes / pharmacokinetics*
Zonula Occludens-1 Protein / genetics
Zonula Occludens-1 Protein / metabolism

Substances

Glucosides
Tjp1 protein, rat
Triterpenes
Zonula Occludens-1 Protein