Pharmacokinetic Study Of Cucurbitacin B From Trichosanthes Cucumerina L. In Rats

Abstract

Cucurbitacin B is a triterpenoid, majorly found in Cucurbitaceae family, particularly in the Trichosanthes cucumerina L. fruits. The pharmacological properties of cucurbitacin B have been studied for decades, particularly an anti-tumor and anti-inflammatory activity. However, the pharmacokinetic profile of this compound is still limited and the investigation is needed for further pharmaceutical product development. This study aimed to investigate the pharmacokinetic profile of cucurbitacin B after administering the compound at different doses and routes to the rats. Male Wistar rats, weighed approximately 400-500 g, were treated with cucurbitacin B extracted from Trichosanthes cucumerina L. The cucurbitacin B was administered at 0.1 mg/kg intravenously or at 1, 2, and 4 mg/kg orally. Blood, urine, feces, and internal organs were collected after administration at a designated time. The level of cucurbitacin B in biological samples was determined by liquid chromatography-tandem mass spectrometry. The absolute oral bioavailability of cucurbitacin B was approximately 10%. The maximum concentration in plasma after normalization by dose ranged from 4.85-7.81 µg/L and the time to reach maximum value was approximately within 30 min after oral dosing. The level of cucurbitacin B in plasma increased proportionally to the given dose. After intravenous administration, cucurbitacin B had a large volume of distribution of about 51.65 L/kg and exhibited a high tissue to plasma concentration ratio, approximately 60 to 280-fold in several organs. A negligible amount of unchanged cucurbitacin B could be detected in urine and feces and accounted for less than 1% of the administered dose. Cucurbitacin B had low oral bioavailability but could be distributed extensively into internal organs with a high volume of distribution and tissue to plasma ratio. Only negligible amounts of unchanged cucurbitacin B were excreted via urine and feces suggesting that the compound might be biotransformed before undergoing an excretion. Further studies of the metabolic pathway and tissue uptake mechanism are required to strategize the future development of cucurbitacin B into clinical studies.