Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent.

Shuang Yang,Yuling Liu,Yan Li,Zhihao Liu,Xuejun Xia,Renyun Wang,Jiaqi Mi,Baolian Wang

doi:10.3390/molecules22101616

Abstract

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ–A (40–1000 mg/kg). The prolonged t1/2 and greater area under concentration-time curve (AUC) versus time (AUC0–t) of DNJ for SZ–A than for purified DNJ has been observed after both oral and intravenous administration. It was found that other components in SZ–A could enhance the absorption of DNJ through the intestinal barrier. The major distribution tissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were mainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was revealed to be partly due to the biotransformation of other components in SZ–A via gut microbiota. These information provide a rational basis for the use of SZ–A in clinical practice.

Highlights

Diabetes mellitus (DM) is a serious disease that can cause a lot of life-threatening health complications [1]
The purpose of this study is to determine the in vivo pharmacokinetic profiles and characteristics of this is toadministration determine the of in SZ–A
The concentration-time curves of three and intravenous (4 mg/kg) administrations of SZ–A are depicted in Figure 2 and the major alkaloids after oral administration of SZ–A at high dose showed the phenomenon of acurves double-peak pharmacokinetic parameters are summarized in Table

Summary

Introduction

Diabetes mellitus (DM) is a serious disease that can cause a lot of life-threatening health complications [1]. Α-glycosidase inhibitors, such as acarbose and miglitol, are widely used for decreasing postprandial hyperglycemia [3]. Postprandial blood glucose control is found to be crucial in the therapy of diabetes. Their gastrointestinal adverse effects were observed during monotherapy or drug combination [4,5]. The effective fraction of alkaloids from traditional Chinese herbal medicine Ramulus Mori The effective fraction of alkaloids from traditional Chinese herbal medicine Ramulus Mori name: Sangzhi), abbreviated to SZ–A, was developed to be an innovative hypoglycemic agent. Its phase (Chinese name: Sangzhi), abbreviated to SZ–A, was developed to be an innovative hypoglycemic

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Methods

Results

Discussion

Conclusion