title: Isojacareubin from the Chinese herb Hypericum japonicum: potent antibacterial and synergistic effects on clinical methicillin-resistant Staphylococcus aureus (MRSA).
abstract: Through bioassay-guided fractionation of the extracts from the aerial parts of the Chinese herb Hypericum japonicum Thunb. Murray, Isojacareubin (ISJ) was characterized as a potent antibacterial compound against the clinical methicillin-resistant Staphylococcus aureus (MRSA). The broth microdilution assay was used to determine the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ISJ alone. The results showed that its MICs/MBCs ranged from 4/16 to 16/64 μg/mL, with the concentrations required to inhibit or kill 50% of the strains (MIC(50)/MBC(50)) at 8/16 μg/mL. Synergistic evaluations of this compound with four conventional antibacterial agents representing different types were performed by the chequerboard and time-kill tests. The chequerboard method showed significant synergy effects when ISJ was combined with Ceftazidime (CAZ), Levofloxacin (LEV) and Ampicillin (AMP), with the values of 50% of the fractional inhibitory concentration indices (FICI(50)) at 0.25, 0.37 and 0.37, respectively. Combined bactericidal activities were also observed in the time-kill dynamic assay. The results showed the ability of ISJ to reduce MRSA viable counts by log(10)CFU/mL at 24 h of incubation at a concentration of 1 × MIC were 1.5 (LEV, additivity), 0.92 (CAZ, indifference) and 0.82 (AMP, indifference), respectively. These in vitro anti-MRSA activities of ISJ alone and its synergy with conventional antibacterial agents demonstrated that ISJ enhanced their efficacy, which is of potential use for single and combinatory therapy of patients infected with MRSA.
authors.affiliation: Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Zuo
authors.affiliation: Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China.|School of Pharmacy, Guiyang Medical University, Guiyang 550004, Guizhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.affiliation: School of Basic Medical Sciences, Yunnan Traditional Chinese Medical College, Kunming 650500, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China.
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Research Center for Natural Medicines, Kunming General Hospital, PLA, Kunming 650032, China.
authors.forename: Gen-Chun
authors.initials: GC
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Guiyang Medical University, Guiyang 550004, Guizhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Hao
authors.affiliation: Center for Infectious Diseases, Kunming General Hospital, PLA, Kunming 650032, China.
authors.forename: Zhong-Qi
authors.initials: ZQ
authors.lastname: Bian
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology; D052978:Disk Diffusion Antimicrobial Tests; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005798:Genes, Bacterial; D020902:Hypericum / Q000737:chemistry; D020128:Inhibitory Concentration 50; D064704:Levofloxacin / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D035261:Plant Components, Aerial / Q000737:chemistry; D014966:Xanthenes / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; D014966:Xanthenes; C458659:isojacareubin; D064704:Levofloxacin; D000667:Ampicillin; D002442:Ceftazidime