Abstract
The development of a new drug is generally marked by a number of preclinical investigations
in a sequential order with regard to contents and logic. However, ethnopharmacology
often uses the “reverse pharmacology” approach, which is based on anecdotal therapeutic
effects of plants in ancient texts or based on the empirical knowledge of traditional
healers. While this approach could successfully lead to new therapeutic applications
by using sophisticated techniques and appropriate bioassays in a logical order, unfortunately
there is an exponentially increasing number of reports of pharmacological effects
of botanical extracts with insignificant bioactivities obtained in often irrelevant
in vitro bioassays. The interpretation based on in vitro data can only be misleading since the pharmacokinetic properties of a compound are
ignored, unacceptable high dosages of extracts are tested, or metabolism to inactive
metabolites is not considered. Further, many natural products are prodrugs that need
to be metabolized in vivo by the intestinal microflora or by mammalian phase I/II metabolism. Frequently, attempts
are made to master poor pharmacokinetics by administering the extract intraperitoneally
or intravenously, clearly moving away from the traditional oral application. In this
review article, it is proposed that preclinical testing strategies of botanicals should
start with the in vivo examination of extracts in relevant animal models to substantiate the ethnopharmacological/ethnopharmaceutical
use, followed by bioguided fractionation processes using an adequate in vitro model, further followed by pharmacokinetic studies and final in vivo testing of isolated compounds. With our article we would like to encourage authors,
reviewers and editors to implement this strategy for the design of experiments and
for the reviewing and editing process of manuscripts.
Key words
preclinical testing - ethnopharmacology - ethnopharmacy - botanicals -
in vivo
-
in vitro
- dosing - application
