Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat

Abstract

Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese medicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and there are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue distribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray ionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues collected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg (corresponding to 42 mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as internal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in rat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference. Moreover, in vivo metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in different time periods after oral and intramuscular administration of icariin. In vivo metabolic pathways were involved in hydrolysis, demethylation, oxidation, and conjugation. The preclinical data would be useful for fully understanding in vivo disposition of this compound and interpreting the mechanism of its biological response.

Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase‐3β‐mediated activation of autophagy

“…Of note, there still remains limitations in this study. First, although icariside II has been proved to cross the blood brain barrier (Xu et al, ), whereas under the I/R condition what percentage of icariside II can cross the blood brain barrier is unknown, as its pharmacokinetic, distribution and metabolism in the brain are unclear. Secondly, icariside II has been suggested to directly bind to PDE 5 and GSK‐3β; whether icariside II can be defined as a dual PDE 5/GSK‐3β inhibitor is worth investigating further.…”

mPEG-icariin nanoparticles for treating myocardial ischaemia

“…ICA has been found effective for treating ischaemic heart disease; however, the clinical application of ICA is limited because of its initial effect and poor water solubility [39]. Research has shown that drug-delivery characteristics could be improved by combining ICA with nano-carrier technology [40,41].…”

“…ICA is extracted from the traditional Chinese medicine plant Epimedium brevicormu maxim(structure in Figure 1). However, ICA is limited in clinical applications because of its first pass elimination and poor water solubility and thus low bioavailability [8,9]. For full pharmacological advantages of ICA, ICA nanoparticles (NPs) have been heavily researched and designed [10,11].…”

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“…The supernatant was evaporated at 45°C in nitrogen gas stream and was reconstituted in 100 µl of mobile phase and injected into the column for the detection of NAR (290nm). [23,24]…”