Abstract
BackgroundCucurbitacin B is the major bioactive constituent in Trichosanthes cucumerina L. fruits, which the pharmacological properties have been studied for decades particularly an anti-tumor activity. The pharmacokinetic profile of this compound is still limited and investigation is needed for further phytopharmaceutical product development. This study aimed to investigate the pharmacokinetic profile of cucurbitacin B after administering the compound at different doses and routes to rats.MethodsMale Wistar rats (n = 6) were treated by cucurbitacin B extracted from Trichosanthes cucumerina L. The cucurbitacin B was administered at 0.1 mg/kg intravenously or by oral gavage at 2–4 mg/kg. Blood samples and internal organs were collected serially within 24 h after administration. Urine and feces were collected from time 0 to 48 h. The level of cucurbitacin B in biological samples was determined by liquid chromatography-tandem mass spectrometry.ResultsThe 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. Negligible amount of unchanged cucurbitacin B could be detected in urine and feces and accounted less than 1% of administered dose.ConclusionCucurbitacin 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.
Highlights
Cucurbitacin B is the major bioactive constituent in Trichosanthes cucumerina L. fruits, which the pharmacological properties have been studied for decades an anti-tumor activity
Method validation Selectivity was determined by analyzing the potential interference that eluted simultaneously with cucurbitacin B and glycyrrhizic acid, the internal standard
Maximum plasma concentration; Tmax, time to maximum plasma concentration; AUC0-t, area under the curve from time zero to last sampling time point; AUC0-inf Area under the curve from time zero to infinity, F Absolute oral bioavailability, volume of distribution (Vd) Volume of distribution, CL Clearance, t1/2 Elimination half-life, mean residence time (MRT) Mean residence time understanding the relationship between the presented amount of the compound in systemic circulation or targeted organs to their therapeutic effects
Summary
Cucurbitacin B is the major bioactive constituent in Trichosanthes cucumerina L. fruits, which the pharmacological properties have been studied for decades an anti-tumor activity. This study aimed to investigate the pharmacokinetic profile of cucurbitacin B after administering the compound at different doses and routes to rats. Various reports confirmed the pharmacological activity of cucurbitacin B. It has been extensively studied in anti-inflammatory [6,7,8], antiatherosclerotic [9], hepatoprotective [10], and antineoplastic activity [4]. The mechanisms of action of cucurbitacin B for anti-cancer properties have been studied for decades; the main mechanisms involved proapoptosis by STAT3 pathway inhibition [11, 12]. Cucurbitacin B could promote cell cycle arrest by mediating multiple signaling pathways, for example, it could induce G2/M cell cycle arrest in breast cancer cells [13, 14] and lung cancer cell line [15]
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