ABSTRACT
Bioactivity-guided fractionation by preliminary screening using interleukin-1β production in lipopolysaccharides (LPS)-induced J774A.1 cell line led to the isolation of fourteen structures including chromone, isocoumarins, flavanoids, and triterpenes from the aerial part of Agrimonia pilosa Ledeb. All structures were determined by measuring their spectroscopic data and comparing their spectroscopic data with the literatures. All the isolates were tested for their inhibitory activities against interleukin-1β production in LPSinduced J774A.1 cell. Of the tested compounds, (S)-(+)-5,7-dihydroxy-2-(1-methylpropyl)chromone (1), agrimonolide-6-O-β-D-glucopyranoside (5), agrimonolide-6-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (6), and catechin (10) were found to be active. Furthermore, compound 1 suppressed the protein expressions of NLRP3 and NLRC4 in murine macrophage.
ABSTRACT
An isoform of NADPH oxidase (NOX), NOX2 is a superoxide-generating enzyme involved in diverse pathophysiological events. Although its potential as a therapeutic target has been validated, there is no clinically available inhibitor. Herein, NOX2-inhibitory activity was screened with the constituents isolated from Schisandra chinensis, which has been reported to have antioxidant and reactive oxygen species (ROS)-scavenging effects. Among the partitions prepared from crude methanolic extract, a chloroform-soluble partition showed the highest NOX2-inhibitory activity in PLB-985 cell-based NOX2 assay. A total of twenty nine compounds (1 – 29) were identified from the chloroform fraction, including two first isolated compounds; dimethyl-malate (25) and 2-(2-hydroxyacetyl) furan (27) from this plants. Of these constituents, two compounds (gomisin T, and pregomisin) exhibited an NOX2-inhibitory effect with the IC₅₀ of 9.4 ± 3.6, and 62.9 ± 11.3 µM, respectively. They are confirmed not to be nonspecific superoxide scavengers in a counter assay using a xanthine-xanthine oxidase system. These findings suggest the potential application of gomisin T (6) and other constituents of S. chinensis to inhibit NOX2.