Nat Prod Sci.  2018 Mar;24(1):59-65. 10.20307/nps.2018.24.1.59.

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

Affiliations
  • 1College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea. f2744@dongguk.edu, mlee@dongguk.edu

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 ICâ‚…â‚€ 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.

Keyword

NADPH oxidase 2 (NOX2); NOX2 inhibitor; Schisandra chinensis; Gomisin T

MeSH Terms

Chloroform
Fruit*
Lignans*
Methanol
NADP*
NADPH Oxidase*
Oxidoreductases
Reactive Oxygen Species
Schisandra*
Superoxides
Chloroform
Lignans
Methanol
NADP
NADPH Oxidase
Oxidoreductases
Reactive Oxygen Species
Superoxides

Figure

  • Fig. 1 Inhibitory effects of S. chinensis extract and its constituents on NOX2. PLB-985 cells were pretreated with (A) methanolic extract of S. chinensis and its partitions or (B) 29 constituents isolated from chloroform partition for 60 min. NOX2 was activated with PMA, and the resultant ROS was measured with Amplex Red for 60 min. Acknowledged NOX inhibitors DPI and VAS2870 were used as a positive control. All values are mean ± standard error (n = 5 for A and 3 for B).

  • Fig. 2 Structures of compounds isolated from the chloroform-soluble extract of S. chinensis.

  • Fig. 3 Concentration-dependent NOX2-inhibitory activity of compounds 6, and 29. PLB-985 cells were pretreated with testing compounds, and PMA-stimulated NOX2 activity was assessed with Amplex Red. Values are mean ± standard error (n = 3 − 4).

  • Fig. 4 Assessment of superoxide-scavenging activity of compounds 6 and 29. Superoxide was produced by xanthine and xanthine oxidase in the presence or absence of testing compound and was quantified with WST-1. Values are mean ± standard error (n = 8).

  • Fig. 5 Effect of compounds 6 and 29 on HRP activity. HRP was treated with the indicated concentrations of compound 6 or 29, and its activity was determined by a colorimetric method using a peroxidase substrate o-dianisidine. The activity of heat-inactivated HRP was measured as a negative control. Values are mean ± standard error (n = 3).


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