Suppression of nitric oxide production in mouse macrophages by soybean flavonoids accumulated in response to nitroprusside and fungal elicitation

Background

The anti-inflammatory properties of some flavonoids have been attributed to their ability to inhibit the production of NO by activated macrophages. Soybean cotyledons accumulate certain flavonoids following elicitation with an extract of the fungal pathogen Diaporthe phaseolorum f. sp. meridionalis (Dpm). Sodium nitroprusside (SNP), a nitric oxide donor, can substitute for Dpm in inducing flavonoid production. In this study, we investigated the effect of flavonoid-containing diffusates obtained from Dpm- and SNP-elicited soybean cotyledons on NO production by lipopolysaccharide (LPS)- and LPS plus interferon-γ (IFNγ)-activated murine macrophages.

Results

Significant inhibition of NO production, measured as nitrite formation, was observed when macrophages were activated in the presence of soybean diffusates from Dpm- or SNP-elicited cotyledons. This inhibition was dependent on the duration of exposure to the elicitor. Daidzein, genistein, luteolin and apigenin, the main flavonoids present in diffusates of elicited cotyledons, suppressed the NO production by LPS + IFNγ activated macrophages in a concentration-dependent manner, with IC₅₀ values of 81.4 μM, 34.5 μM, 38.6 μM and 10.4 μM respectively. For macrophages activated with LPS alone, the IC₅₀ values were 40.0 μM, 16.6 μM, 10.4 μM and 2.8 μM, respectively. Western blot analysis showed that iNOS expression was not affected by daidzein, was reduced by genistein, and was abolished by apigenin, luteolin and Dpm- and SNP-soybean diffusates at concentrations that significantly inhibited NO production by activated macrophages.

Conclusions

These results suggest that the suppressive effect of flavonoids on iNOS expression could account for the potent inhibitory effect of Dpm- and SNP-diffusates on NO production by activated macrophages. Since the physiological concentration of flavonoids in plants is normally low, the treatment of soybean tissues with SNP may provide a simple method for substantially increasing the concentration of metabolites that are beneficial for the treatment of chronic inflammatory diseases associated with NO production.

     

The stability properties ofq-step backward difference schemes

We present a new proof that aq-step backward difference scheme for the approximate solution of a first order ordinary differential equation is stable in the sense of Dahlquist iff 1q6.The only other proof known to the authors was given by Cryer in a condensed version with most proofs omitted of a much larger technical report.     

Measurement of the fundamental thermal noise limit in a cryogenic sapphire frequency standard using bimodal maser oscillations

We report observations of the Schawlow-Townes noise limit in a cryogenic sapphire secondary frequency standard. The effect causes a fundamental limit to the frequency stability, and was measured through the novel excitation of a bimodal maser oscillation of a Whispering Gallery doublet at 12.04 GHz. The beat frequency of 10 kHz between the oscillations enabled a sensitive probe for this measurement of fractional frequency instability of 10(-14) tau(-1/2) with only 0.5 pW of output power.     

Four-wave mixing from Fe3+ spins in sapphire

Fe(3+) ions in sapphire exhibit an electron spin resonance which interacts strongly with high-Q whispering gallery modes at microwave frequencies. We report the first observation of a third-order paramagnetic nonlinear susceptibility in such a resonator at cryogenic temperatures and the first demonstration of four-wave mixing using this parametric nonlinearity. This observation of an all-microwave nonlinearity is an enabling step towards a host of quantum measurement and control applications which utilize spins in solids.