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 EcNfsA 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, urolithin 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 (K_i < 2 μmol·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 bacterial nitroreductase.
Ellagic Acid/pharmacology* ; Escherichia coli ; Kinetics ; Nitroreductases/pharmacology* ; Plant Extracts/pharmacology* ; Syzygium

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.
Animals ; Colitis/drug therapy* ; Mesalamine/pharmacology* ; Mice ; Nitroreductases ; Oleanolic Acid/pharmacology* ; Prodrugs

Bacterial Proteins ; Humans ; Metronidazole/pharmacology* ; Mycobacterium tuberculosis ; NAD ; Nitroreductases ; Tuberculosis, Lymph Node

OBJECTIVETo demonstrate the correlation of rdxA gene mutation and metronidazole (MTZ) resistance of H.pylori isolates in the local area.

METHODSClinical strains of H.pylori were isolated from gastric biopsy of patients. Resistance to metronidazole of the isolates was determined by using diffusion test and two fold dilution test. Genome DNAs of the isolates were prepared for PCR to detect rdxA gene. The target amplification products were sequenced after T-A cloning. The sequences were compared with the reported sequences from Hp26695 and 134 other strains of H.pylori.

RESULTSMTZ resistance rate was 76.1% in 21 clinical isolates. The target fragment 886 bp in length containing rdxA gene could be successfully amplified. In comparison with the reported corresponding sequence of H.pylori stain 26695, homologies of the nucleotide sequences from the amplification products were 90.1% approximate, equals 95.1%. Mutations caused by base insertion/deletion and substitution in the MTZ resistance isolates were found. Among these mutations, two types of insertion mutations have not been reported in literatures. No same mutations were present in the MTZ sensitive isolates.

CONCLUSIONThe rdxA gene mutation may play an important role in MTZ resistance of H.pylori.

Amino Acid Sequence ; Drug Resistance, Bacterial ; Helicobacter pylori ; drug effects ; genetics ; Metronidazole ; pharmacology ; Molecular Sequence Data ; Mutation ; Nitroreductases ; chemistry ; genetics