Neuroprotective extract fractions and single substances from Sideritis scardica in the nematode Caenorhabditis elegans, an in-vivo model for neurodegenerative diseases

Hydroethanolic extracts of Sideritis scardica Griseb. (Lamiaceae), widely known as Greek mountain tea, have repeatedly shown CNS-associated activities, such as enhancement of cognitive performance [1] and ameliorating effects on pathomechanisms of neurodegenerative diseases [2]-[4]. To investigate the active principle in terms of neuroprotection, we chose Caenorhabditis elegans to examine the in-vivo activity of six extract fractions (prepared by liquid-liquid extraction, re-precipitation in ethanol and solid-liquid separation of a 40% ethanolic primary extract of aerial parts) as well as seven single compounds occurring in S. scardica. The transgenic C. elegans strain CL2355 expresses pan-neuronal human amyloid-β, leading to a degeneration of nerve cells involved in chemotactic behavior. The chemotaxis index of the worms significantly increased when treated with the polar-lipophilic fractions or polar, phenolic compounds belonging to the class of phenylethanoid glycosides, including acteoside. Exactly the same pattern was observed in two further assays: These fractions and substances also protected dopaminergic neurons of strain BZ555 from 6-OHDA-induced degeneration (quantifiable through fluorescence intensity) and they reduced the number of aggregates of Q40::YFP, a polyglutamine peptide, in strain AM141. The investigated mechanisms are linked to neurodegeneration in Alzheimer’s, Parkinson’s, and Huntington’s disease, respectively, and were positively influenced by neuroprotective properties of polar-lipophilic S. scardica extract fractions and phenylethanoids. In each case, the measured significant effects did not exceed the activity of the primary extract itself. That indicates a relevant contribution to the overall efficacy of crude, hydroethanolic extracts, which themselves, representing multi-substance mixtures, we regard as the active principle of Sideritis scardica.

• References

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