Pharmacokinetics, tissue distribution and excretion of verticinone from F. hupehensis in rats.

Xiao Wu,Hui Chen,Ji-Zhou Wu,Guang-Ji Wang,Yan Liang,Peng Zhang,Ying Peng,Jian-Guo Sun

doi:10.3390/molecules191220613

Xiao Wu, Hui Chen + Show 6 more

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https://doi.org/10.3390/molecules191220613

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Abstract

Verticinone, the main active component in F. hupehensis, exhibits potent antitussive and expectorant effects. Here, a LC-MS method was developed and applied to study the pharmacokinetics, tissue distribution and excretion of verticinone in rats, and its plasma protein binding in vitro. A significant gender difference in the pharmacokinetics of verticinone in rats was observed, as its absolute oral bioavailability in male and female rats was 45.8% and 2.74%, respectively. The relative bioavailability of verticinone was significantly lower in female rats as compared to male, following intragastrical (i.g.) and intravenous (i.v.) administration. After successive i.g. administration of verticinone, accumulation was observed in female rats but not in the male ones. The tissue distribution study showed that verticinone had a good tissue penetrability and a high tissue affinity in most studied tissues, except brain. After a 2 mg/kg oral dose, less than 4% of the dose was excreted as unchanged parent compound in male rats, and less than 1% in female rats, which indicated that verticinone was metabolized more extensively in female rats than in male rats.

Highlights

Beimu, the dried bulbs of various Fritillaria species, has been used in Traditional Chinese Medicine as an important antitussive and expectorant herb for more than 2000 years
The time-concentration curves of verticinone following i.g. and i.v. administration are shown in Figures 2 and 3
The curves fitted well a two-compartmental model after i.g. dose and a three-compartmental model after i.v. dose based on the Akaike information criterion (AIC)

Summary

Introduction

The dried bulbs of various Fritillaria species, has been used in Traditional Chinese Medicine as an important antitussive and expectorant herb for more than 2000 years. Verticinone (Figure 1) is the main alkaloid in F. hupehensis Hsiao et KC Hsia (Hubei Beimu), with a content of about 0.3% in the crude herb. It has potent antitussive and expectorant activities [5], and no addictive effect in mice [6,7]. Verticinone has antitumor [2,8] and analgesic effects [7]. Due to the potent antitussive activity and no addictive effect, verticinone seems to be a promising potential antitussive drug

Results

Discussion

Conclusion