| Summary: | Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. <i>Momordica charantia</i> L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, <b>6</b>) along with 25ξ-isopropenylchole-5(6)-ene-3-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (<b>1</b>), karaviloside VI (<b>2</b>), karaviloside VIII (<b>3</b>), momordicoside L (<b>4</b>), momordicoside A (<b>5</b>) and kuguaglycoside C (<b>7</b>) from an Indian cultivar of <i>Momordica charantia</i>. At 50 µM compounds, <b>2</b>–<b>6</b> differentially affected the expression of pro-inflammatory markers <i>IL-6</i>, <i>TNF-α</i>, and <i>iNOS</i>, and mitochondrial marker <i>COX-2</i>. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase.
|
|---|