Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn, Thailand.
Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Drug Des Devel Ther. 2024 Jul 11;18:2905-2917. doi: 10.2147/DDDT.S453847. eCollection 2024.
Our previous studies in vitro and in vivo have shown anti-severe acute respiratory syndrome coronavirus 2 activity of fingerroot extract () and its phytochemical panduratin A.
Therefore, the objective of this study was to determine the pharmacokinetic profiles of panduratin A, as a pure compound and in fingerroot extract, in rats.
Male rats were randomly divided into four groups. Rats underwent intravenous administration of 4.5 mg/kg panduratin A, a single oral administration of 45 mg/kg panduratin A, or a multiple oral administration of 45 mg/kg panduratin A-consisted fingerroot extract for 7 consecutive days. The concentrations of panduratin A in plasma, tissues, and excreta were measured by using LCMS with a validated method.
The rats showed no change in health status after receiving all test preparations. The absolute oral bioavailability of panduratin A administered as pure panduratin A and fingerroot extract were approximately 9% and 6%, respectively. The peak concentrations for the single oral doses of 45 mg/kg panduratin A and fingerroot extract, were 4833 ± 659 and 3269 ± 819 µg/L, respectively. Panduratin A was mostly distributed in gastrointestinal organs, with the highest tissue-to-plasma ratio in the stomach. Approximately 20-30% of unchanged panduratin A from the administered dose was detected in feces while a negligible amount was found in urine. The major metabolites of administered panduratin A were identified in feces as oxidation and dioxidation products.
Panduratin A from fingerroot extract showed low oral bioavailability, good tissue distribution, and partially biotransformed before excretion via feces. These findings will assist in developing fingerroot extract as a phytopharmaceutical product for COVID-19 treatment.
我们之前的体外和体内研究表明，莪术提取物及其植物化学物质莪术二酮具有抗严重急性呼吸系统综合征冠状病毒 2 的活性。
因此，本研究的目的是确定莪术二酮作为纯化合物和莪术提取物在大鼠中的药代动力学特征。
雄性大鼠随机分为四组。大鼠分别静脉注射 4.5mg/kg 莪术二酮、单次口服 45mg/kg 莪术二酮、或连续 7 天口服 45mg/kg 莪术二酮组成的莪术提取物。采用 LCMS 结合验证方法测定血浆、组织和排泄物中莪术二酮的浓度。
大鼠在接受所有测试制剂后健康状况无变化。纯莪术二酮和莪术提取物口服给药的绝对生物利用度分别约为 9%和 6%。单次口服 45mg/kg 莪术二酮和莪术提取物的峰浓度分别为 4833±659 和 3269±819μg/L。莪术二酮主要分布在胃肠道器官，胃中的组织与血浆比最高。从给予剂量中检测到的未改变的莪术二酮约有 20-30%在粪便中，而在尿液中几乎检测不到。给予的莪术二酮的主要代谢物在粪便中被鉴定为氧化和二氧化产物。
莪术提取物中的莪术二酮显示出低口服生物利用度、良好的组织分布，并在通过粪便排泄前部分生物转化。这些发现将有助于将莪术提取物开发为治疗 COVID-19 的植物药产品。
