Nitric oxide inhibitory principles from Derris trifoliata stems

Nine rotenoids were isolated from the hexane and dichloromethane extracts of Derris trifoliata stems and were tested for nitric oxide (NO) inhibitory activity using RAW264.7 cells. The result indicated that 12a-hydroxyrotenone (7) possessed very potent NO inhibitory activity with an IC50 value of 0.002 mu M, followed by 1 (deguelin, IC50 = 0.008 mu M), 9 (12a-hydroxyelliptone, IC50 = 0.010 mu M) and 2 (alpha-toxicarol, IC50 = 0.013 mu M), respectively. In addition, the DPPH scavenging activity of rotenoids was also investigated. It was found that 6a,12a-dehydrodeguelin (5) possessed the highest activity against DPPH with an IC50 value of 7.4 mu M, followed by deguelin (1, IC50 = 27.4 mu M). All compounds did not show any cytotoxicity at their IC50 values for NO inhibitory activity. Structure-activity relationships (SARs) of these rotenoids against NO release are as follows: (1) hydroxylation at C12a dramatically increased activity, (2) prenylation at furan ring increased activity markedly and (3) hydrogenation of a double bond at C6a-C12a conferred higher activity. For the DPPH radical scavenging effect, it was found that (1) introduction of a double bond at C6a-C12a increased activity and (2) hydroxylation of C11 at the D-ring decreased activity. As regards active compounds of Derris trifoliata stems, the isolated compounds are responsible for the NO inhibitory effect, especially 7, 1, 9 and 2, whereas 5 and 1 are those for the DPPH scavenging activity. (C) 2008 Elsevier GmbH. All rights reserved.