Phytochemical and pharmacological characterization of plant extracts containing flavones with antidepressant activity

Screening throughput is an important requirement in the early phases of a drug discovery program because it determines the ability to evaluate a large number of compounds and, thereby, the discovery of new pharmaceuticals. The dominant drug discovery paradigm for synthetic drugs is the mechanism-based screening using in-vitro tests for the lead identification. This approach is a superior strategy for well-validated targets with defined mechanism of action, but has limitations for the development of symptomatic treatments in indications with an unclear or multifactorial aetiology. In this cases a screening approach, based on biological efficacy in a disease model, seems to be more rewarding because it can identify compounds with novel or unknown modes of action. However, the limitation of this strategy is the low screening capacity because most of the disease models are time consuming in-vivo tests.

Aim of our investigation was the development of a new antidepressant plant extract based on the content of flavone glycosides with demonstrated antidepressant activity like hyperosid, isorhamnetin or rutin. As disease model we used the rat „forced swimming test“ (FST) with a treatment period of 9-days. Selection of extracts was based on the analysis of chromatograms by gradient HPLC of raw extracts and its acidic hydrolysates. The quantification of the formed aglycons (quercetin, isorhamnetin and kaempferol) in combination with an interesting glycoside pattern established a priority list for testing. Evaluation of 279 total extracts, 355 special extracts and 321 hydrolysats of methanol extracts lead to the selection of 32 extracts for in-vivo testing. Although all the tested extracts contained high amounts of flavonoids described to be effective in the FST only twelve of the 32 extracts were found to be active in our hands. There was no correlation between the concentration of single flavonoids and the efficacy in the FST test. Thus, it seems that the different spectrum of flavonoid glycosides in combination with other ingredients is responsible for the efficacy in the FST or that different flavonoids act synergistically in this animal model.