Isojacareubin from the Chinese Herb Hypericum japonicum: Potent Antibacterial and Synergistic Effects on Clinical Methicillin-Resistant Staphylococcus aureus (MRSA)

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Zuo, Guo-Ying ; An, Jing ; Han, Jun ; Zhang, Yun-Ling ; Wang, Gen-Chun ; Hao, Xiao-Yan ; Bian, Zhong-Qi (2012)
  • Publisher: Molecular Diversity Preservation International
  • Journal: International Journal of Molecular Sciences, volume 13, issue 7, pages 8,210-8,218 (issn: 1422-0067, eissn: 1422-0067)
  • Related identifiers: pmc: PMC3430230, doi: 10.3390/ijms13078210
  • Subject: Chemistry | Hypericum japonicum | synergy | &lt;em&gt;Hypericum japonicum&lt;/em&gt; | Isojacareubin | anti-MRSA activity | MIC | QD1-999 | Article | Biology (General) | QH301-705.5 | <em>Hypericum japonicum</em>

Through bioassay-guided fractionation of the extracts from the aerial parts of the Chinese herb &lt;em&gt;Hypericum japonicum&lt;/em&gt; Thunb. Murray, Isojacareubin (ISJ) was characterized as a potent antibacterial compound against the clinical methicillin-resistant S&lt;em&gt;taphylococcus aureus&lt;/em&gt; (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&lt;sub&gt;50&lt;/sub&gt;/MBC&lt;sub&gt;50&lt;/sub&gt;) 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&lt;sub&gt;50&lt;/sub&gt;) 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&lt;sub&gt;10&lt;/sub&gt;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 &lt;em&gt;in vitro&lt;/em&gt; 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.
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