Bioavailability and disposition kinetic of Cucurbitacin B in rats

Abstract

Background: Cucurbitacin B is an oxygen-rich containing triterpene which can be found mainly in Trichosanthes cucumerina. Cucurbitacin B gains some interests due to it exerts numerous pharmacological effects particularly antiinflammation and antitumor activity. Although Cucurbitacin B has been studied extensively in its pharmacological properties, the pharmacokinetic information in mammals of Cucurbitacin B is very limited. Thereby, this study aims to investigate the pharmacokinetic profiles of Cucurbitacin B given intravenously and orally at different therapeutic doses in rats.Methods: 24 male Wistar rats were treated by Cucurbitacin B extracted from Trichosanthes cucumerina fruit juice (90.7 %purity). The Cucurbitacin B was administered either at 0.1 mg/kg intravenously or by oral gavage at 1, 2, or 4 mg/kg to the Wistar rats. Blood samples and internal organs were collected serially after administration at different time points throughout 24 hours. Moreover, urine and feces were also collected from time 0 to 48 hours. The level of Cucurbitacin B in biological samples was determined by liquid chromatography-tandem mass spectrometry. Results: The oral absolute bioavailability of Cucurbitacin B was 10 %. The highest concentration in plasma ranged from 1 -100 ng/mL and reached maximum value approximately within 30 minutes. The level of Cucurbitacin B in plasma increased proportionally to the given dose. This can be concluded that Cucurbitacin B possesses the linear pharmacokinetics. The results also demonstrated that Cucurbitacin B had a large volume of distribution (Vd = 51.65 ± 39.16 L) and exhibited a high tissue to plasma ratio, accounting around 10-fold in several organs. Only trivial amount of unchanged Cucurbitacin B could be detected in urine and feces accounted less than 1% of the given dose. Conclusion: Cucurbitacin B has low oral absolute bioavailability, but it can distribute extensively into other organs. Cucurbitacin B is not excreted mainly in unchanged form both in urine and feces suggesting that it may be metabolized by hepatic or intestinal enzymes before undergoing an excretion. Further studies about possible metabolic pathway and tissue uptake mechanism are required to strategize the future development of Cucurbitacin B use in human.

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“…Cucurbitacin B is the most studied compound among all cucurbitacins, and hence, the literature information about the bioavailability and safety of this compound is the most comprehensive. Experiments with Wistar rats have shown that the oral bioavailability of cucurbitacin B was 10%, with the highest concentration in plasma ranging from 1 to 100 ng/mL and reaching maximum value approximately within 30 min [380]. Moreover, cucurbitacin B displayed a high tissue-to-plasma ratio, accumulating around 10-fold in several organs.…”