Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts—Computational and Experimental Investigations

Abstract

The root of <i>Geranium collinum</i> Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of <i>G. collinum</i>. The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC₅₀ values of 0.10 μg/mL and 0.09 μg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of <i>G. collinum</i>, led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra-<i>O</i>-methylellagic acid (<b>1</b>), 3,3'-di-<i>O</i>-methylellagic acid (<b>2</b>), quercetin (<b>3</b>), caffeic acid (<b>4</b>), (+)-catechin (<b>5</b>), (-)-epicatechin (<b>6</b>), (-)-epigallocatechin (<b>7</b>), gallic acid (<b>8</b>), β-sitosterol-3-<i>O</i>-β-d-glucopyranoside (<b>9</b>), and corilagin (<b>10</b>). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC₅₀ values below 0.9 μg/mL, more effective than the positive control (1.46 μg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and β-sitosterol-3-<i>O</i>-β-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of <i>G. collinum</i> is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from <i>G. collinum</i> shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of <i>G. collinum.</i>