A new isoflavonoid glycoside and other constituents from Tilia amurensis with anti-neuroinflammatory activity

Abstract

Tilia amuresnsis Rupr. is a tree traditionally used in Korean medicine. Its leaves have been used as tea for health purposes [1]. As part of our ongoing search for bioactive constituents of natural Korean medicinal resources, we found in a preliminary study that the MeOH extract from the trunks of T. amurensis showed an inhibitory effect on nitric oxide (NO) production in an activated murine microglial cell line. A bioassay-guided fractionation and chemical investigation of the MeOH extract resulted in the isolation and identification of a new isoflavonoid glycoside, orobol 4'-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1) and 16 known compounds (2-17). The structure of the new compound was determined by spectroscopic methods, namely 1D and 2D NMR techniques, HRMS, and chemical methods. Anti-neuroinflammatory activities of the isolated compounds were determined by measuring NO levels in the medium using murine microglia BV-2 cells. Among them, twelve compounds, including compound 1 (most active with an IC50 value of 23.42 µM), inhibited NO production in lipopolysaccharide-stimulated BV-2. Moreover, compounds 1-4 showed moderate anti-proliferative activities against the SK-MEL-2 cell line with IC50 values ranging from 12.31 to 19.67 µM.