Anti-mutagenicity of Swertiamarin and Its Metabolite in Incubated System of Human Intestinal Flora

Objective To study the biotransformation regulation and pharmacological effect of swertiamarin and its metabolite in incubated system of human intestinal flora. Methods Incubated system of human intestinal flora was utilized to research the intestinal metabolism of swertiamarin. Furthermore, mutagenic test and anti-mutagenic test were carried out to research the activity relationship of swertiamarin and its metabolite. Results Gentianine was found in the metabolites of swertiamarin. The pharmacological experiment indicated that swertiamarin and its metabolite both had good anti-mutagenic effect. Conclusion Swertiamarin is partly metabolized to gentianine after oral administration. They show similar anti-mutagenicity effects.

Inhibitory effects of the ferment liquids on sarcoma

Objective： To study the anti-tumor effects of the ferment liquid （FL） and to explore the anti-mutagenic effects induced by cyclophosphamide （CP）. Methods： Anti-tumor effects and Anti-mutagenic effects induced by cyclophosphamide （CP） of the ferment liquid were observed in tumor-bearing mice in vivo. Spleen lymphocytes proliferation of mice was stimulated by ConA and NK cell activity was analyzed by the lactate dehydrogenase （LDH） release assay. Results： FL Ⅰ,FL Ⅱ and FL Ⅲ of 16.7, 33.3 and 66.6 ml/kg inhibited growth of Sarcoma 180 sighificanth by 11.6%, 24.2%, 28.0%, 4.8%, 15.2%, 2.2% and 2.1%, 8.5%, 5.2% respectively. Polychromatic erythrocytes （PCE） at all doses of FL Ⅰ and FL Ⅱ were greatly decreased compared with control group （ P 〈 0.05）, but FL Ⅲ has no inhibition effents（ P 〉 0.05）. Production of IL-2 showed no significant difference between all treatment groups. The NK cell killing activity in all treated mice increased by FL Ⅰ and FL Ⅱ was significantly potentiated compared to controls （ P 〈 0.05）. Lymphocytes proliferation of ICR mice were stimulated by ConA 2.5 ml/L and there were no differences between groups. Conclusion： The present data suggested that three kinds of ferment liquid used as health drink have anfi-mutagenesis, immune enhancement effects and showed certain inhibitory effects on S180 tumor growth in vivo.

Inhibition of Escherichia coli nitroreductase by the constituents in Syzygium aromaticum

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds,hydroxylamines or aromatic amines,most of which are carcinogenic and mutagenic agents.Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon,so as to prevent colon diseases.In this study,the inhibitory effects of 55 herbal medicines against Escherichia coli(E.coli)nitroreductase(EcNfsA)were examined.Compared with other herbal extracts,Syzygium aromaticum extract showed superior inhibitory potency toward EcNf-sA mediated nitrofurazone reduction.Then,the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted.Compared with other tested natural compounds,ellagic acid,corilagin,betulinic acid,oleanic acid,ursolic acid,urolith-in M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA,with IC50 values ranging from 0.67 to 28.98 mol·L^(−1).Furthermore,the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA(Ki<2μmol·L−1)in a competitively inhibitory manner,which created strong interactions with the catalytic triad of EcNfsA.In summary,our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum,where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacteri-al nitroreductase.