In vivo pharmacokinetics comparisons of icariin, emodin and psoralen from Gan-kang granules and extracts of Herba Epimedii, Nepal dock root, Ficus hirta yahl

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Abstract

Ethnopharmacological relevance

Gan-kang granules (GKG) contains the extracts from eight Chinese herbs and is a traditional Chinese composite prescription for treatment of hepatitis B. Icariin, emodin and psoralen are main effective ingredients of the medicine.

Aim of the study

In this research, pharmacokinetic comparisons of icariin, emodin and psoralen from the extracts of Herba Epimedii, Nepal dock root and Ficus hirta yahl, and GKG were conducted.

Materials and methods

At different time points (0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 and 24 h) after administration, the concentrations of icariin, emodin and psoralen in rat plasma were determined by HPLC-UV, and main pharmacokinetic parameters were estimated.

Results

The pharmacokinetic parameters of icariin, emodin and psoralen in GKG were elevated comparing with those of herb extracts.

Conclusions

Three HPLC-UV methods were developed successfully for the analysis of icariin, emodin and psoralen in SD rat plasma. Some ingredients in GKG may increase the dissolution and absorption, and improve bioavailability of icariin, emodin and psoralen in rats.

Introduction

Traditional Chinese medicine (TCM) has been applied in clinical practice for over 2000 years. Because of the complexity and unknown effective ingredients, the development of TCM is faced with many difficulties. Pharmacokinetic studies on TCM play an important role in explaining and predicting efficacy and toxicity of TCM.

Pharmacokinetic study of TCM has developed rapidly in the past 10 years. Most researches (Lee et al., 2003a, Lee et al., 2003b, Si et al., 2008, Zhang et al., 2008) were focused on pharmacokinetic studies by using mono-ingredient or single herb extract over past years. However, it may not represent the pharmacokinetics of the whole composite prescription. Thus, it is better to select several effective ingredients as the targets to investigate the pharmacokinetics of the whole prescription, and compare the pharmacokinetic differences between single and multiple components (Lu et al., 2007, Guo et al., 2008, Xu et al., 2008).

GKG is a traditional Chinese composite prescription containing Actinidia arguta roots (Actinidia arguta (Sieb. et Zucc.) Planch. ex Miq., Actinidiaceae), Rabdosin serra Hara (Isodon lophanthoides (Buch.-Ham.exD.Don) H.Hara), Radix Astragali (Astragalus mongbolicus (Bge.) Hsiao, Leguminosae), Fructus Crataegi (Crataegus pinnatifida Bge. Rosales), Mahonia bealei (fort.) Carr (Mahonia bealei(Fort)Carr., Berberis), Herba Epimedii (Epimedium brevicornum Maxim., Berberis), Nepal dock root (Rumex japonicus Houtt., Polygonaceae), Ficus hirta yahl (Psoralea corylifolia L., Leguminosae), among which Herba Epimedii, Nepal dock root and Ficus hirta yahl are three key ingredient herbs. The main bioactive components and pharmacologic action of GKG are given in Table 1. It has been proved that GKG is a safe and effective drug in the treatment of hepatitis B (Tang et al., 2005, Chen et al., 2006). Icariin, emodin and psoralen are the main effective compounds of the three herbs and have been used as phytochemical markers for the quality control. Their structures are given in Fig. 1.

Pharmacokinetic studies on icariin (Cheng et al., 2007, Tu et al., 2008), emodin (Lee et al., 2003a, Lee et al., 2003b) and psoralen (Huang et al., 1991, Pang et al., 2001, Xia et al., 2008) in some herb extracts have been carried out. However, the pharmacokinetic studies on those three ingredients in composite prescription were seldom reported. In this paper, we developed three simple and rapid HPLC methods to determine the concentrations of icariin, emodin and psoralen in rat plasma after intragastric administration of the extracts of Herba Epimedii, Nepal dock root and Ficus hirta yahl and GKG, respectively. The aim of this research is to obtain pharmacokinetic parameters and the possible pharmacokinetic differences of the three ingredients after administration of single herb extract and GKG, and explore whether there are synergistic effects on the three ingredients in GKG.

Section snippets

Materials and reagents

Herba Epimedii, Nepal dock root and Ficus hirta yahl were purchased from Shaoyang (Hunan, China). The raw herbs were certified by Hunan Provincial Institute for Drug Control (Hunan, China). Icariin, emodin, psoralen, antipyrine benzoate (HPLC grade, internal standard), 2-methyl-anthraquinone (HPLC grade, internal standard), alficetin (HPLC grade, internal standard) were supplied by the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Methanol,

Specificity

Fig. 2, Fig. 3, Fig. 4 shows that no interference peaks from endogenous constituents were detected, respectively.

Linearity of calibration curve and lower limit of quantification

Calibration curves showed excellent linearity in the range 0.0638–10.2 μg/ml for icaiin, 0.05–10 μg/ml for emodin and 0.0625–10.0 μg/ml for psoralen in rat plasma. Typical equations for the calibration curves were: Y = 0.0413X + 0.0006, r = 0.9997 for icariin, Y = 0.0164X − 0.0002, r = 0.9991 for emodin and Y = 0.0493X + 0.0048, r = 0.9993 for psoralen. The LLOQ was found to be 0.0638 μg/ml for icariin,

Iicariin pharmacokinetic parameters

We know that icariin was distributed as opened two-compartment model after intragastric administration of Herba Epimedii extract and GKG. The pharmacokinetic parameters of icariin after administration of GKG, in comparison with Herba Epimedii extract alone, show a higher Cmax (3.13 ± 0.29 μg/ml versus 2.41 ± 0.20 μg/ml, P < 0.01), a higher AUC0–∞ (30.84 ± 3.68 μg h ml−1 versus 23.62 ± 1.37 μg h ml−1, P < 0.01), a longer Tmax (2.06 ± 0.15 h versus 1.55 ± 0.53 h, P < 0.05) and a longer t1/2(a) (0.35 ± 0.32 h versus 0.11 ± 0.07 h,

Conclusion

Three sensitive, specific and accurate HPLC-UV methods were developed for the analysis of icariin, emodin and psoralen in SD rat plasma. These methods have advantages of satisfactory selectivity, recovery, precision, stability, robustness and simple sample preparation. The analytical procedure was then successfully applied to the pharmacokinetic study of icariin, emodin and psoralen in rats after intragastric administration of GKG and single herb extract. It plays an important role in

Acknowledgements

We thank to Natural Science Fund of Hunan Province. We thank to Dr. Hengming Ke at University of North Carolina at Chapel Hill, USA for critical proofreading this manuscript. We thank to Dr. Tang Yijia and Quanfang Pharmaceutical Company for financial support.

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