Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens Thunb extract in rats

作者：Wen, Binyu; He, Rong; Li, Pengyue; Xu, Qihua; Lu, Yanli; Peng, Bo; Li, Jianrong^*

来源：Journal of Ethnopharmacology, 2013, 147(2): 503-508.

DOI：10.1016/j.jep.2013.03.048

• Ajuga decumbens Thunb extract
• 8-O-acetylharpagide
• Harpagide
• Pharmacokinetics
• Metabolite

Ethnopharmacological relevance: Ajuga decumbens Thunb is a medicinal plant native to China popularly used to treat chronic pelvic inflammation and hysteromyoma. Its main bioactive components are iridoid glycosides, such as 8-O-acetylharpagide and harpagide that had presented antibacterial, anti-inflammatory, and antiviral activities.
Aim of the study: To establish a sensitive LC-MS/MS method and compare the pharmacokinetics of 8-O-acetylharpagide and harpagide in rats after oral administration of their pure forms and from compounds obtained from Ajuga decumbens extract.
Materials and methods: Rats received orally 15 mg/kg (equivalent of 6 mg/kg 8-O-acetylharpagide and 1.5 mg/kg harpagide), 30 mg/kg and 60 mg/kg of Ajuga decumbens Thunb extract and were compared to animals that received 12 mg/kg of 8-O-acetylharpagide or 3 mg/kg of harpagide p.o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartmental analysis.
Results: Results showed that the iridoid glycosides were quickly absorbed by oral route and showed a dose-dependence profile. Pharmacokinetic parameters of both glycosides were essentially the same except Tmax when dosed as the extract or pure forms.
Conclusion: 8-O-acetylharpagide was metabolized to harpagide, which affected the pharmacokinetic profiles of harpagide when dosed as the extract. This pharmacokinetic study seems to be useful for a further clinical study of Ajuga decumbens Thunb extract.

• 出版日期2013-5-20
• 单位中国中医科学院