Zhang Chun-Nan, Wang Zhi-Bin, Du Rui-Tong, Zhang Shu-Lu, Wang Chu-Qiao, Wang Meng, Wu Li-Hong, Yang De-Qiang, Wang Chen
Traditional Chinese Medicine Department, Heilongjiang Provincial Hospital, Harbin, China.
Key Laboratory of Basic and Application Research of Beiyao, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, China.
Front Pharmacol. 2025 Sep 10;16:1647015. doi: 10.3389/fphar.2025.1647015. eCollection 2025.
Cucurbitacin, a class of triterpenoid compounds isolated from , possesses various biological activities and is the primary active component of cucurbitacin tablets (CUT) used to treat chronic hepatitis and primary liver cancer. Nanosuspensions can potentially improve the oral bioavailability of pharmacopotent substances. This is the first study comparing the pharmacokinetics of three cucurbitacin triterpenoids (cucurbitacin B [CuB], cucurbitacin D [CuD], and cucurbitacin E [CuE] following oral administration of CUT and a novel . nanosuspension (MP-NPs) in rats.
The plasma concentrations of these cucurbitacin triterpenoids were quantified through ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A selective, simple, and sensitive UHPLC-MS/MS method was developed using the positive ion mode for multiple reaction monitoring analysis. The chromatographic column used was Waters Acquity HSS T3 (1.8 μm, 2.1 × 100 mm), the column temperature was 35 °C, the flow rate was 0.3 mL/min, the injection volume was 5 μL, and the mobile phase was a gradient elution of water (A) and methanol (B). The intra- and inter-day precision for all analytes was <13%, and accuracy ranged from -6.41% to -4.01.
According to the pharmacokinetic results, when the two rat groups were orally administered with the same dose of CUT and MP-NPs, the elimination half-life ( ) of CuD and CuE was longer than that of CuB, indicating slower elimination. Compared with the CUT group, the triterpenoids in the MP-NPs group reached the maximum plasma concentration ( ) within 2 h, and both and the area under the plasma concentration increased significantly.
The MP-NPs formulation significantly enhanced the oral bioavailability of cucurbitacin triterpenoids compared to conventional CUT. These findings underscore the potential of nanosuspension technology in improving the pharmacokinetic profile of cucurbitacin-based therapeutics. This study provides valuable insights for further development and clinical application of cucurbitacin nanosuspensions.
葫芦素是从[具体来源未给出]中分离出的一类三萜类化合物，具有多种生物活性，是用于治疗慢性肝炎和原发性肝癌的葫芦素片（CUT）的主要活性成分。纳米混悬液有可能提高药效物质的口服生物利用度。这是第一项比较大鼠口服CUT和新型纳米混悬液（MP-NPs）后三种葫芦素三萜（葫芦素B [CuB]、葫芦素D [CuD]和葫芦素E [CuE]）药代动力学的研究。
通过超高效液相色谱-串联质谱（UHPLC-MS/MS）对这些葫芦素三萜的血浆浓度进行定量。采用正离子模式进行多反应监测分析，建立了一种选择性、简单且灵敏的UHPLC-MS/MS方法。所用色谱柱为Waters Acquity HSS T3（1.8μm，2.1×100mm），柱温为35℃，流速为0.3mL/min，进样量为5μL，流动相为水（A）和甲醇（B）的梯度洗脱。所有分析物的日内和日间精密度均<13%，准确度范围为-6.41%至-4.01。
根据药代动力学结果，当两组大鼠口服相同剂量的CUT和MP-NPs时，CuD和CuE的消除半衰期（ ）长于CuB，表明消除较慢。与CUT组相比，MP-NPs组的三萜类化合物在2小时内达到最大血浆浓度（ ），且 和血浆浓度-时间曲线下面积均显著增加。
与传统的CUT相比，MP-NPs制剂显著提高了葫芦素三萜的口服生物利用度。这些发现强调了纳米混悬液技术在改善基于葫芦素的治疗药物药代动力学方面的潜力。本研究为葫芦素纳米混悬液的进一步开发和临床应用提供了有价值的见解。
