Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Loew, D. et al.

Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo.

PURPOSE: Harpagophytum extract and its marker substance harpagoside were shown to exert anti- inflammatory effects by interacting with the eicosanoid biosynthesis. In this study, different Harphagophytum extracts were tested with respect to inhibition of leukotriene and thromboxane biosynthesis in vitro and ex vivo. In addition, pharmacokinetic parameters of Harpagophytum extracts were investigated in vivo.Methods And Subjects: Different fractions of Harpagophytum extracts were tested in vitro in human whole blood samples for effects on basal and ionophore A23187-stimulated cysteinyl-leukotriene (Cys-LT) and thromboxane synthesis. Furthermore, in 3 independent studies with different numbers of human male volunteers, a Harpagophytum extract was administered orally and tested in whole blood samples for Cys-LT and thromboxane B2 (TXB2) biosynthesis and for the determination of pharmacokinetic parameters of harpagoside. RESULTS: The special Harpagophytum extract WS1531 had a stronger inhibitory effect on ionophore A23187-stimulated Cys-LT levels compared with pure harpagoside or other extract fractions. Fractions without harpagoside had no pronounced inhibitory effect. When Cys-LT levels were measured after oral intake of Harpagophytum extract, a biphasic but dose-independent decrease of 28% and 58%, respectively, in basal Cys-LT formation was observed. Pharmacokinetic studies with the Harpagophytum extract WS1531 showed that the maximum levels of plasma harpagoside were reached after 1.3 to 2.5 hours. A linear relationship between dose and the first maximal concentration (Cmax) or area under the curve (AUC) (0-1)/AUC(0-infinity) was observed. CONCLUSIONS: Our observations strongly indicate a close relation between serum harpagoside levels and the inhibition of leukotriene biosynthesis.[1]

References

Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Loew, D., Möllerfeld, J., Schrödter, A., Puttkammer, S., Kaszkin, M. Clin. Pharmacol. Ther. (2001) [Pubmed]

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