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

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 1.5mg/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 3mg/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.