The disconnection approach: integrationism and reductionism in the study of medicinal plants

Nowadays there have been numerous discussions about the reductionist and integrationist (or holistic) approaches in the search of new biologically active compounds [1]. In this study, we propose the combination of both approaches to investigate the mode of action of the medicinal plant Tithonia diversifolia (Hemsl). A. Gray (Asteraceae) through the „disconnection approach“, i.e. the receipt of different plant extracts from a biological matrix and further dereplication. Leaves of T. diversifolia, which are traditionally used as anti-inflammatory remedy, were used to obtain the following extracts: aqueous crude extract by infusion of entire leaves; leaf rinse extract [2] by rinsing entire dried leaves with acetone; 70% methanol extract of powdered leaves without glands. The essential oil was obtained by steam distillation of leaves. The extracts and their main isolated compounds were evaluated using in vivo (subchronic toxicity in rats, paw oedema and croton oil assays in mice) and in vitro (MPO activity, NO, IL, TNF-α, etc.) models while the essential oil was evaluated by the croton oil assay. The dereplication using HPLC-DAD-MS/MS indicated flavonoids, chlorogenic acids and sesquiterpene lactones (STLs) in the extracts while mono and sesquiterpenes were identified in the essential oil by GC-MS. The extracts and the oil showed anti-inflammatory activity while the products containing STLs were found to be toxic; not only STLs are involved in the anti-inflammatory activity as expected [3]. As conclusion, using the disconnection approach it was possible to find out which classes of compounds are related to a certain biological property as well as to propose modes of action.

Acknowledgements: FAPESP, CAPES and CNPq.

References: 1. Peterson, RT (2008) Nat. Chem. Biol. 11: 635–638.

2. Ambrósio, S.R. et al. (2008) Phytochemistry 69: 2052–2060.

3. Valério, D.A.R. et al. (2007) Eur. J. Pharmacol. 562: 155–163.