Aureonitol Analogues and Orsellinic Acid Esters Isolated from <i>Chaetomium elatum</i> and Their Antineuroinflammatory Activity

Abstract

Overexpression of various pro-inflammatory factors in microglial cells tends to induce neurodegenerative diseases, for which there is no effective therapy available. Aureonitol (<b>1</b>) and seven analogues, including six previously undescribed [elatumenol A-F (<b>2</b>-<b>4</b>, <b>6</b>-<b>8</b>, respectively)], along with two new orsellinic acid esters [elatumone A and B (<b>9</b> and <b>10</b>)], were isolated from <i>Chaetomium elatum</i>. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including high-resolution mass spectra and one- and two-dimensional NMR, and absolute configurations determined by the Mosher method, dimolybdenum tetraacetate-induced circular dichroism, and theoretical calculations including electronic circular dichroism and NMR. Metabolites <b>3</b>, <b>4</b>, <b>7</b>, and <b>8</b> exhibited antineuroinflammatory activity by attenuating the production of inflammatory mediators, such as nitric oxide, interleukin-6, interleukin-1β, tumor necrosis factor-α, and reactive oxygen species. Western blot results indicated <b>8</b> decreases the level of inducible nitric oxide synthase and cyclooxygenase-2 and suppresses the expression of Toll-like receptor 4 and nuclear factor kappa-B (NF-κB) as well as the phosphorylation of the inhibitor of NF-κB and p38 mitogen-activated protein kinases in lipopolysaccharide-activated BV-2 microglial cells.