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Metabolite identification and pharmacokinetic study of platycodi radix (Jiegeng) in vivo

机译:桔梗(Jiegeng)体内 的代谢产物鉴定和药代动力学研究

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Platycodi radix (Jiegeng) is commonly used as a channel ushering drug for assistance in treating respiratory diseases, because of the activities of saponins that are called platycosides. In this study, using ultra high pressure liquid chromatography with quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS) and a strategy based on fragmentation behaviors, a total of thirteen platycosides were identified in the total saponins, and seven of these were found in rat plasma following a single oral dose of total saponins. The secondary platycosides were proved to be the main absorbed saponins in vivo. The major absorbed platycosides, 3-O-β-D-glucopyranosylplatyconic acid (GPA) and 3-O-β-D-glucopyranosylplatycodigenin (GP), were isolated from total saponins and the pharmacokinetics were evaluated in mice by liquid chromatography with triple quadrupole mass spectrometry (LC-QQQ). The results of the pharmacokinetic analysis indicated that GPA and GP were quickly absorbed with short Tmax (<45 min). Cmax (μg L?1), AUC0–t (μg h L?1) and MRT0–t (h) of GPA were 1147.75 ± 307.23, 2119.16 ± 530.84 and 4.10 ± 0.33 at a dose of 105 mg kg?1, and 3673.10 ± 1250.44, 8734.07 ± 2362.48 and 3.95 ± 0.82 at a dose of 350 mg kg?1. The above pharmacokinetic parameters were higher than those of GP at the same dosage, which showed that GPA was likely to be the main absorbed saponin in vivo. These findings provide useful information that will support the studies on identification of bioactive platycosides in vivo, and will lay the foundation for the development of Jiegeng.
机译:Platycodi radix(Jiegeng)由于被称为platycosides的皂苷的活性,通常被用作辅助治疗呼吸道疾病的通道引导药物。在这项研究中,使用具有四极杆飞行时间质谱(UPLC-Q / TOF-MS)的超高压液相色谱法和基于碎片行为的策略,在总皂苷中总共鉴定出13种桔梗苷,其中7种单次口服总皂苷后,在大鼠血浆中发现了维生素D。已证明次生桔梗是体内主要吸收的皂苷。主要吸收的桔梗3- O -β- D -吡喃葡萄糖基铂酸(GPA)和3- O -β- D从总皂苷中分离出-吡喃葡萄糖基铂二糖苷原(GP),并通过液相色谱-三重四极杆质谱(LC-QQQ)对小鼠的药代动力学进行了评估。药代动力学分析结果表明,GPA和GP被 T max 短时(<45分钟)迅速吸收。 C max (μgL ?1 ),AUC 0– t (μgh L ?1 )和MRT 0– t (h)在剂量为105 mg kg ?1时的GPA为1147.75±307.23、2119.16±530.84和4.10±0.33 sup> 和3673.10±1250.44、8734.07±2362.48和3.95±0.82(剂量为350 mg kg ?1 )。在相同剂量下,上述药代动力学参数均高于GP,这表明GPA可能是体内主要吸收的皂苷。这些发现提供了有用的信息,将支持对体内生物活性白石棉的鉴定研究,为解庚的发展奠定基础。

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