Effects of isoflavones and soybeans fermented with Bacillus subtilis on lipopolysaccharide-induced production of tumor necrosis factor-alpha and fibrinolysis in vivo.

The effects of isoflavones and of a derivative of soybeans fermented with Bacillus subtilis, designated Nattoesse, on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) and fibrinolysis were investigated in vivo. The dietary supplement Nattoesse contains several isoflavones. Therefore, we examined the effects of individual isoflavones (daidzein, daidzin, genistein, and genistin) on the LPS-induced production of TNF-alpha. Intraperitoneal injections of daidzein, daidzin, and genistin (but not of genistein before a challenge with LPS) resulted in significant depression of serum levels of TNF-alpha in mice. Daidzein had the strongest activity in this assay. Oral administration of daidzein to mice also had a significant suppressive effect, as compared with that of the Citrus flavanone naringin. In galactosamine-sensitized mice, by contrast, the suppression of LPS-induced lethal shock by daidzein was very weak. Nattoesse did not inhibit the production of TNF-alpha nor did it prevent lethal shock. However, oral administration of Nattoesse to mice significantly suppressed LPS-induced increases in scores of the fibrin degradation product, and the effect was both dose- and time-dependent. Thus, it appears that Nattoesse has fibrinolytic activity during LPS-induced circulatory failure.