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高良姜主要生物活性成分化合物D在大鼠体内的药代动力学

Pharmacokinetics of Compound D, the Major Bioactive Component of Zingiber cassumunar, in Rats.

作者信息

Khemawoot Phisit, Hunsakunachai Natthaphon, Anukunwithaya Tosapol, Bangphumi Kunan, Ongpipattanakul Boonsri, Jiratchariyakul Weena, Soawakontha Ruedee, Inthachart Thanakorn, Dechatiwongse Na Ayudhya Thaweephol, Koontongkaew Sittichai, Poachanukoon Orapan

机构信息

Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

出版信息

Planta Med. 2016 Aug;82(13):1186-91. doi: 10.1055/s-0042-104658. Epub 2016 Apr 28.

Abstract

Rhizomes of Zingiber cassumunar have been used for many years in traditional Thai medicine as an anti-inflammatory agent. The major bioactive component of this plant is Compound D [E-4-(3', 4'-dimethoxyphenyl)but-3-en-1-ol], which is a strong smooth muscle relaxant, and has antihistamine and anti-inflammatory actions. There is, however, incomplete information available for the pharmacokinetics of Compound D in mammals. In this study, we examined the pharmacokinetic profiles of Compound D in male Wistar rats. A standardized extract of Z. cassumunar containing 4 % w/w Compound D was administered intravenously at 25 mg/kg or by oral gavage at 25, 75, or 250 mg/kg to Wistar rats. Blood, tissues, urine, and feces were collected from 0 to 48 h after dosing and the level of Compound D was determined by liquid chromatography-tandem mass spectrometry. The concentration of Compound D ranged from 10-100 µg/L, reached a maximum approximately 0.15 h after oral dosing. Compound D exhibited an excellent tissue to plasma ratio, ranging from 1- to 1000 in several organs at 1-4 h after oral dosing. Less than 1 % of unchanged Compound D was excreted in the urine and feces. Further studies on tissue uptake and metabolite identification are required to obtain complete pharmacokinetic information and to develop appropriate dosing strategies of Compound D and the standardized extract of Z. cassumunar.

摘要

多年来,泰国传统医学一直将高良姜的根茎用作抗炎剂。这种植物的主要生物活性成分是化合物D [E-4-(3', 4'-二甲氧基苯基)丁-3-烯-1-醇],它是一种强效的平滑肌松弛剂,具有抗组胺和抗炎作用。然而,关于化合物D在哺乳动物体内的药代动力学信息并不完整。在本研究中,我们检测了化合物D在雄性Wistar大鼠体内的药代动力学特征。将含有4% w/w化合物D的高良姜标准化提取物以25 mg/kg的剂量静脉注射或分别以25、75或250 mg/kg的剂量灌胃给予Wistar大鼠。给药后0至48小时收集血液、组织、尿液和粪便,采用液相色谱-串联质谱法测定化合物D的含量。化合物D的浓度范围为10-100 μg/L,口服给药后约0.15小时达到最大值。化合物D表现出良好的组织与血浆比值,口服给药后1至4小时在几个器官中的比值范围为1至1000。尿液和粪便中排出的未变化的化合物D不到1%。需要进一步研究组织摄取和代谢物鉴定,以获得完整的药代动力学信息,并制定化合物D和高良姜标准化提取物的合适给药策略。

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