Salunkhe Ruchira, Gadgoli Chhaya, Naik Archana, Patil Nikita
Saraswathi Vidya Bhavan's College of Pharmacy, Dombivli, India.
Front Pharmacol. 2021 Apr 29;12:629272. doi: 10.3389/fphar.2021.629272. eCollection 2021.
Diosgenin, charantin, and hydroxychalcone are utilized for standardization of popular antidiabetic herbal drugs L belonging to family Fabaceae, L belonging to family Cucurbitaceae, and J. Presl belonging to family Lauraceae. However, no reports on the bioavailability of these markers were available. The present study was undertaken to determine the bioavailability and pharmacokinetic profile of the markers and formulations containing the herbs. The pharmacokinetic profile and absolute bioavailability of the pure active markers were determined in male Wistar rats by administrating individually the doses of 1.5 mg/kg i.v. and 15 mg/kg p.o., followed by estimation of serum levels of the markers at 0, 10, 30, 60, 120, and 240 mins till 24 h time points by a validated bioanalytical HPTLC method. Two standardized antidiabetic capsule formulations containing spray dried hydroalcoholic extracts of seeds of L. (42.8 mg equivalent to 0.95%w/w of diosgenin), fresh fruits of L. (21.4 mg equivalent to 0.4% w/w of charantin), and bark of J. Presl (10.71 mg equivalent to 0.079 %w/w hydroxychalcone) were prepared. In one formulation, piperine 1.5 mg was added along with the other herbal extracts mentioned. Bioavailability and pharmacokinetic profile of these two formulations were determined in male Wistar rats through estimating serum levels of active markers diosgenin, charantin, and hydroxychalcone at 0, 10, 30, 60, 120, and 240 mins till 24 h later oral administration of the formulations (Formulation without piperine F1 and formulation with Piperine F2). Plasma concentrations were found to decline mono-exponentially following intravenous administration, and the mean elimination half-life (t) was observed to be 7.93, 8.21, and 4.66 h, respectively. The absolute oral bioavailability of pure markers was observed to be 9.0 ± 0.2%, 8.18 ± 0.36%, and 10.54 ± 0.52% by the dose normalization method. The oral bioavailabilities of the formulations with respect to diosgenin, charantin, and hydroxychalcone were found to be 9.78, 10.743, and 8.07%, respectively. The formulation containing piperine indicated a significant ( < 0.01) increase in the bioavailabilities of all the marker compounds. In conclusion, diosgenin and charantin have low bioavailabilities as compared to hydroxychalcone. The bioavailabilities of all the three marker compounds can be increased exponentially with the addition of piperine.
薯蓣皂苷元、葫芦素和羟基查耳酮被用于对豆科、葫芦科和樟科的常见抗糖尿病草药进行标准化。然而，关于这些标志物生物利用度的报道尚无。本研究旨在确定这些标志物以及含草药制剂的生物利用度和药代动力学特征。通过分别静脉注射1.5mg/kg和口服15mg/kg剂量，然后采用经过验证的生物分析高效薄层色谱法在0、10、30、60、120和240分钟直至24小时时间点估算标志物的血清水平，来测定雄性Wistar大鼠中纯活性标志物的药代动力学特征和绝对生物利用度。制备了两种标准化抗糖尿病胶囊制剂，一种含有豆科种子喷雾干燥的水醇提取物（42.8mg相当于0.95%w/w的薯蓣皂苷元）、葫芦科新鲜果实（21.4mg相当于0.4%w/w的葫芦素）和樟科树皮（10.71mg相当于0.079%w/w的羟基查耳酮）。在一种制剂中，加入了1.5mg胡椒碱以及上述其他草药提取物。通过在口服制剂（不含胡椒碱的制剂F1和含胡椒碱的制剂F2）后0、10、30、60、120和240分钟直至24小时估算活性标志物薯蓣皂苷元、葫芦素和羟基查耳酮的血清水平，来测定这两种制剂在雄性Wistar大鼠中的生物利用度和药代动力学特征。静脉注射后血浆浓度呈单指数下降，平均消除半衰期（t）分别观察到为7.93、8. and 4.66小时。通过剂量归一化法观察到纯标志物的绝对口服生物利用度分别为9.0±0.2%、8.18±0.36%和10.54±0.52%。发现含胡椒碱制剂中薯蓣皂苷元、葫芦素和羟基查耳酮的口服生物利用度分别为9.78%、10.743%和8.07%。含胡椒碱的制剂表明所有标志物化合物的生物利用度均有显著（<0.01）提高。总之，与羟基查耳酮相比，薯蓣皂苷元和葫芦素的生物利用度较低。添加胡椒碱可使所有三种标志物化合物的生物利用度呈指数增加。
