Lignans with NADPH Oxidase 2 (NOX2)-inhibitory Activity from the Fruits of Schisandra chinensis

• Published in: Natural product sciences Vol. 24; no. 1; pp. 59 - 65
• Main Authors: Park, Jung-Min, Pel, Pisey, Chin, Young-Won, Lee, Moo-Yeol
• Format: Journal Article
• Language: Korean
• Published: 2018
• Subjects: Schisandra chinensis; NADPH oxidase 2 (NOX2); NOX2 inhibitor; Gomisin T
• ISSN: 1226-3907

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 $IC_{50}$ of $9.4{\pm}3.6$, and $62.9{\pm}11.3{\mu}M$, 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.