Frontiers in Pharmacology · 2021 · 15 citations · 48 references
Medicinal plant extracts are becoming increasingly important as an alternative for traditional drugs against diabetes mellitus (DM). For this reason, we initialized a target-based screening of 111 root extracts from an open access plant extract library (PECKISH) by ascertaining their <i>in-vitro</i> inhibitory efficacy on α-glucosidase. The two most active extracts <i>Geum urbanum</i> L. (roseroot) and <i>Rhodiola rosea</i> L. (avens root) were further tested for their antidiabetic activities in terms of their impact on different regulatory key points of glucose homeostasis. To this end, various enzyme- and cell culture-based <i>in-vitro</i> assays were employed including the determination of sodium-dependent glucose transporter 1 (SGLT1) activity in Caco-2 monolayers by Ussing chambers and of glucose transporter 4 (GLUT4) translocation in a GFP-reporter cell line. Subsequently, the antidiabetic potential of the root extracts were further evaluated in <i>in-vivo</i> models, namely hen's eggs test and the fruit fly <i>Drosophila melanogaster</i>. Avens root extract was found to be a more potent inhibitor of the enzymes α-glucosidase and dipeptidyl peptidase-4 (DPP4) than roseroot extract. Most importantly, only avens root extract exhibited antidiabetic activity in the two <i>in-vivo</i> models eliciting a reduced blood glucose level in the <i>in-ovo</i> model and a decline of the triglyceride level in a dietary starch-induced <i>D. melanogaster</i> obesity model. Analyses of the polyphenolic composition of the avens root extract by HPLC revealed a high content of ellagic acid and its derivatives as well as ellagitannins such as pedunculagin, stenophyllanin, stachyurin, casuarinin and gemin A. In conclusion, avens root extract represents a promising medicinal plant that should be considered in further <i>in-vivo</i> studies on hyperglycemia in laboratory rodents and humans.
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