Growth-Inhibiting, Bactericidal, and Urease Inhibitory Effects of Paeonia lactiflora Root Constituents and Related Compounds on Antibiotic-Susceptible and -Resistant Strains of Helicobacter pylori

An assessment was made of the growth-inhibiting, bactericidal, and urease inhibitory activities of paeonol (PA), benzoic acid (BA), methyl gallate (MG), and 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (PGG) identified in Paeonia lactiflora root, structurally related compounds, and four antibiotics toward three reference strains and four clinical isolates of Helicobacter pylori using broth dilution bioassay and Western blot. BA and PA showed strong bactericidal effect at pH 4, while MG and PGG were effective at pH 7. These constituents exhibited strong growth-inhibiting and bactericidal activity toward the five strains resistant to amoxicillin (minimal inhibitory concentration (MIC) 12.5 mg/L), clarithromycin (64 mg/L), metronidazole (64 mg/L), or tetracycline (15 mg/L), indicating that these constituents and the antibiotics do not share a common mode of action. Structural characteristics, such as types of functional groups and carbon skeleton, and hydrophobicity appear to play a role in determining the anti-H. pylori activity. H. pylori urease inhibitory activity of PGG was comparable to that of acetohydroxamic acid, while MG was less potent at inhibiting urease than thiourea. The UreB band disappeared at 250 mg/L PGG on Western blot, while the UreA bands were faintly visible at 1000 mg/L PGG. These constituents showed no significant cytotoxicity. Global efforts to reduce the level of antibiotics justify further studies on P. lactiflora root-derived materials containing MG, PA, and PGG as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by H. pylori.