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 (MIC50/MBC50) 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 (FICI50) 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 log10CFU/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.

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“…An 85% ethanol-treated water extract is documented in the Chinese Pharmacopoeia as an injection for the treatment of viral hepatitis [2, 3]. Moreover, H. japonicum is used as an animal feed in China because of its widespread growth.…”

Antimicrobial activity and synergy of antibiotics with two biphenyl compounds, protosappanins A and B from Sappan Lignum against methicillin-resistant Staphylococcus aureus strains

“…The MICs (mg/L) of PsA and PsB used in combination with the five clinically used antibiotics, including the FICIs of each combination against the 10 MRSA strains are shown in Table . The synergistic interactions with the antibiotics were evaluated through the classical checkerboard method (Table ) and time‐kill curve method (Table and Figure ) [15,16]. There were eight and five MRSA strains that showed synergy in the two combinations of PsA and PsB with Ak, respectively.…”

“…Further exploring the new constituents against MRSA in Sappan Lignum led us to find PsA and PsB as another two active compounds from its ethanol extract through bioactivity‐guided isolation and identification [28–30]. The present study reports the evaluation of these two compounds for their potential synergistic effects with conventional antibiotics against clinical MRSA strains through the checkerboard and time‐kill curve methods [14–16]…”

“…Potential interactions of PsA and PsB in combination with various antibiotics against MRSA were evaluated by determination of fractional inhibitory concentration indices (FICIs) and time‐kill curves through the use of a checkerboard and dynamic time‐kill methods, as described previously [14–16]. The bacteriostatic interaction mode was judged by FICIs as follows: FICI ≤ 0.5, synergy; 0.5 < FICI ≤ 1, additive; and 1 < FICI < 2, indifferent (or no effect) and FICI ≥ 2, antagonism [38,39].…”

Diversity and bioactive potential of endophytic fungi from Nothapodytes foetida, Hypericum mysorense and Hypericum japonicum collected from Western Ghats of India

“…Some bioactive chemicals like salothranols, saropyrone, salothralens, sarolactones, taxifolin-7-Orhamnoside, isoquercitrin, quercitrin, chromone glycosides, quercetin and kaempferol have been characterized in H. japonicum. This plant is also known for its antioxidant properties (Samaga and Rai 2013a;Zuo et al 2012).…”