Evaluation of Metabolic Stability of Kinsenoside, an Antidiabetic Candidate, in Rat and Human Liver Microsomes

Shaheed Ur Rehman,Min Sun Choi,Hye Hyun Yoo,N Sook Kim,Yongbo Xue,Yonghui Zhang,Guangming Yao,Zengwei Luo

doi:10.5478/msl.2015.6.2.48

Abstract

Kinsenoside is a principle bioactive compound of Anoectochilus formosanus. It exhibits various pharmacological effects such as antihyperglycemic, antioxidant, anti-inflammatory, immunostimulating, and hepatoprotective activities and has recently been developed as an antidiabetic drug candidate. In this study, as part of an in vitro pharmacokinetic study, the stability of kinsenoside in rat and human liver microsomes was evaluated. Kinsenoside was found to have good metabolic stability in both rat and human liver microsomes. These results will provide useful information for further in vivo pharmacokinetic and metabolism studies.

Highlights

As possibility remains that kinsenoside may have active metabolite(s), based on knowledge regarding the in vivo pharmacological activity of kinsenoside,[4,5,6] the metabolic stability study with liver microsomes would provide a useful information on this
Chemical stability of kinsenoside To evaluate the non-enzymatic degradability of kinsenoside, kinsenoside was incubated in distilled water and 0.1 M potassium phosphate buffer and the amount of kinsenoside remaining was measured (Figure 3)
Ten micromolar kinsenoside exhibited the same degree of degradation. These results show that non-enzymatic degradation of kinsenoside does not occur under these conditions

Summary

Introduction

Kinsenoside [3-(R)-3-β-D-glucopyranosyloxybutanolide] is a principle bioactive compound of Anoectochilus formosanus (Orchidaceae), an important ethnomedicinal plant in Asian countries such as China and Taiwan.[1,2,3] Kinsenoside exhibits a variety of pharmacological actions, including antioxidant, antiinflammatory, immunostimulating, hepatoprotective, and osteoclast formation inhibiting activities.[3,4,5,6,7] In particular, it has potent antihyperglycemic activity[3]; in addition, it inhibits the increase in body and liver weights, significantly reduces triglyceride levels in the liver,[1] and reduces vascular damage under high glucose conditions.[8]. As part of an in vitro pharmacokinetic study, the stability of kinsenoside in rat and human liver microsomes was evaluated. Kinsenoside was found to have good metabolic stability in both rat and human liver microsomes.

Results

Conclusion