[Show abstract][Hide abstract] ABSTRACT: Background:
Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays.
The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments.
ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25.
ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.
Preview · Article · Dec 2015 · BMC Complementary and Alternative Medicine
[Show abstract][Hide abstract] ABSTRACT: Salvianolate (SAL) is a prescribed medicine from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It has been widely used in treatment of coronary and other diseases with significant effects. The in vitro antimicrobial activities of SAL against infectious pathogens were assayed and its combined effects on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA) with ten antibiotics were evaluated. Susceptibility to each agent alone was tested using a broth microdilution method, and the chequerboard and time-kill experiments were used for the combined activities. The results showed MIC was 128-256 mg/L for SAL used alone against MRSA. Significant synergies were observed for SAL/ Ampicillin (Fosfomycin, Erythromycin, Piperacillin-tazobactam or Clindamycin) combination against over half of the isolates, with their MICs reduced by times of dilution (TOD) to 4-32 (FICIs 0.375-0.5), respectively. SAL/ AMP combination showed the best combined effect of synergy on bacteriostatic and bactericidal activities, while SAL/ AMK combination reversed the resistance of MRSA to AMK. The results demonstrated that SAL enhanced widely the in vitro anti-MRSA efficacy of the ten antibacterial agents, which had potential for combinatory therapy of patients infected with MRSA and warrants further investigations.
Preview · Article · Nov 2015 · Journal of Pharmacological Sciences
[Show abstract][Hide abstract] ABSTRACT: One new flavonoid, 5,6,7-trimethoxyflavone-8-O-β-d-glucopyranoside (1), along with six known compounds 2-7, was isolated from Oroxylum indicum. Their structures were determined on the basis of spectral data. The antibacterial activities of compounds 1-4 were studied. Compounds 1 and 3 showed medium antibacterial activity against Staphylococcus aureus with MIC/MBC at 32-128 μg/ml.
Full-text · Article · Feb 2015 · Natural Product Research
[Show abstract][Hide abstract] ABSTRACT: A new limonoid, 3-de(2-methylbutanoyl)-3-propanoylcipadesin (1), along with 10 known limonoids and 1 known triterpenoid, was isolated from the fruits of Cipadessa cinerascens. Their structures were elucidated on the basis of spectroscopic analysis. All compounds were evaluated for their antimicrobial activities, and compounds 6 and 12 showed weak antimicrobial activities against MRSA 82(#) and MRSA 92(#).
No preview · Article · Jun 2014 · Journal of Asian Natural Products Research
[Show abstract][Hide abstract] ABSTRACT: One Myrioneuron alkaloid, myrifabine (1), the first example of a dimer with 12 chiral centers embraced in a decacyclic novel skeleton, was isolated from Myrioneuron faberi . Its structure was elucidated by spectroscopic data and single-crystal X-ray diffraction. The antimicrobial and cytotoxic activities of 1 were evaluated in vitro.
[Show abstract][Hide abstract] ABSTRACT: Four new terpenoids, nemoralisins D-G (1-4), were isolated from the leaves and stems of Aphanamixis grandifolia, along with two known diterpenoids, nemoralisin C and nemoralisin. Among them, compound 1 is the first example of norsesquiterpenoid with δ-lactone moiety, and nemoralisins E-G (2-4), are a class of acyclic diterpenoids, which are structurally related nemoralisin C and nemoralisin. These structures were established on the basis of spectroscopic methods and the absolute configuration of 1 was determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Nemoralisins D-G (1-4) were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines (IC50>40 μM), as well as the antimicrobial activities on Staphylococcus aureus, Pseudomonas aeruginosa, MRSA92(#) and MRSA98(#) (MIC>50 μg/mL).
[Show abstract][Hide abstract] ABSTRACT: Two new compounds, khayseneganin I (1) and 2α,3α,16β-trihydroxy-20-acetoxy-20(R)-pregnane (2), along with six known compounds, 2α,3α,20-trihydroxy-16β-acetoxy-20(R)-pregnane (3), 2α,3β-dihydroxypregnan-16-one-2β,19-hemiketal (4), (+)-catechin (5), ivorenolide A (6), luteolin-7-O-α-l-rhamnoside (7), and ( - )-5'-methoxy-isolariciresinol-2a-O-β-d-xylopyranoside (8), were isolated from the leaves and twigs of Khaya senegalensis. The structures of new compounds were elucidated by 2D NMR spectroscopy and MS. Selected compounds (2-8) were evaluated for their antimicrobial activities and compounds 5 and 7 showed weak antimicrobial activities against MRSA 92(#) and MRSA 98(#).
Full-text · Article · May 2013 · Journal of Asian natural products research
[Show abstract][Hide abstract] ABSTRACT: N-Methyl-dihydroberberine (M-Ber) was synthesized, and antibacterial activities of Berberine (Ber) and M-Ber alone and combined with antibiotics were studied against ten clinical MRSA isolates. MICs/MBCs (μg/ml, alone) ranges were 32–128/64–256 (Ber) and 64–128/256–1,024 (M-Ber) by a broth microdilution method. Significant synergies of Ber (M-Ber)/Azithromycin and Ber (M-Ber)/Levofloxacin combinations were observed by the chequerboard test. The Ber (M-Ber)/Ampicillin and Ber (M-Ber)/Cefazolin combinations showed indifference. These results demonstrated that Ber and M-Ber enhanced the in vitro inhibitory efficacy of Azithromycin and Levofloxacin, which had potential for combinatory therapy of patients infected with MRSA.
No preview · Article · May 2013 · Medicinal Chemistry Research
[Show abstract][Hide abstract] ABSTRACT: Two new daphnicyclidin-type Daphniphyllum alkaloids, daphmacrodins A and B (1 and 2) were isolated from the leaves and stems of Daphniphyllum macropodum. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. The relative configuration of 1 was further confirmed by a single-crystal X-ray diffraction analysis. Their cytotoxic activities against five human cancer cell lines, pesticidal activities against brine shrimp (Artemia salina), and antibacterial activities against five standard bacterial and fungal strains were evaluated. The structure of 1 was successfully transformed to 2 by a chemical method.
Electronic Supplementary Material
Supplementary material is available for this article at 10.1007/s13659-012-0095-z and is accessible for authorized users.
[Show abstract][Hide abstract] 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.
Preview · Article · Dec 2012 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: The in vitro antimicrobial activities of 30 Chinese medicinal plants were evaluated with reference to the treatment record of infectious diseases in the Traditional Chinese Medicine (TCM) literature. The plant materials were extracted with 80% ethanol and the extracts were primarily screened against conventional clinical pathogens like Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans by the agar diffusion method. Their inhibition zone diameters (IZDs, mm, 50 mg/mL) ranged from 2,048 by the standard broth microdilution method. The seven extracts from M. yunnanensis, S. sinensis, G. morella, E. daneillii, M. squamulata, S. arborescens and B. hancei were determined as the most active extracts, with MICs of 8-64 μg/mL. The results were in good agreement with their traditional applications in skin and other infections.
[Show abstract][Hide abstract] ABSTRACT: Antibacterial activity of berberine (Ber) and 8-acetonyl-dihydroberberine (A-Ber) alone and combined uses with antibacterial agents ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) was studied on 10 clinical isolates of SCCmec III type methicillin-resistant Staphylococcus aureus (MRSA). Susceptibility to each agent alone was tested using a broth microdilution method and the chequerboard and time-kill tests for the combined evaluations, respectively. The alone MICs/MBCs (μg/mL) ranges were 32-128/64-256 (Ber) and 32-128/128-512 (A-Ber). Significant synergies were observed for the Ber (A-Ber)/AZM and Ber (A-Ber)/LEV combinations against 90% of the tested MRSA strains, with fractional inhibitory concentration indices (FICIs) values ranged from 0.188 to 0.500. An additivity result was also observed for the Ber/AZM combination by time-kill curves. These results demonstrated for the first time that Ber and A-Ber enhanced the in vitro inhibitory efficacy of AZM and LEV to a same extent, which had potential for further investigation in combinatory therapeutic applications of patients infected with MRSA.
[Show abstract][Hide abstract] ABSTRACT: Two new degraded diterpenoids, trigohowilols A (1) and B (2), four new heterodimers, trigohowilols C-F (3-6), one new homodimer, trigohowilol G (7), and three known degraded diterpenoids (8-10) were isolated from the methanol extract of the stems of Trigonostemon howii. Compounds 1-7 were evaluated for their cytotoxic activity against five human tumor cell lines by an MTT assay, and trigohowilols E (5) and F (6) exhibited inhibitory activity with IC(50) values ranging from 2.33 to 12.57 μM. Moreover, compounds 1-6 showed weak antimicrobial activities (MIC values: 6.25-25 μg/mL) against Staphylococcus aureus, Pseudomonas aeruginosa, MRSA 92(#), and MRSA 98(#) using a 2-fold dilution method.
No preview · Article · Nov 2012 · Journal of Natural Products
[Show abstract][Hide abstract] ABSTRACT: In vitro activities of 80% ethanol extracts from 26 plants native to South-Eastern Yunnan, China, were evaluated against clinical multi-drug resistant (MDR) pathogens. The extracts were initially screened by the agar hole diffusion test. Then the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum fungicidal concentration (MFCs) were determined through serial dilution with a standard broth micro-dilution method. Of the 26 extracts, 9 showed different potencies against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. The most active plants against both S. aureus and methicillin-resistant S. aureus (MRSA) were Rhodoleia parvipetala Tong, Diplopanax stachyanthus Hand.-Mazz and Sarcosperma kachinense Exell var. simondii Lam.et Royen, and their MIC/MBCs were 512, 512, 256-512 mg/L, respectively. Sladenia celastrifolia Kurz extract showed strong activity against P. aeruginosa and C. albicans, and their MICs were 512-2048 and 2048 mg/L, together with no activities of MBC or MFC up to the concentrations of 2048 mg/L. All these plants showed weak inhibition against E. coli.
Preview · Article · May 2012 · African journal of microbiology research
[Show abstract][Hide abstract] ABSTRACT: Trigoflavidols A (1) and B (2), tetranorditerpenoid dimers possessing a rearrangement skeleton with a spiroketal core moiety, and trigoflavidol C (3), a hexanorditerpenoid, have been isolated from Trigonostemon flavidus along with two known compounds. Compounds 1 and 2 showed moderate antimicrobial activities (MIC values: 3.12-6.25 μg/mL) against Staphylococcus aureus, 8(#)MRSA, and 82(#)MRSA, and 1, 2, and 5 showed weak activities (IC(50) values: 3.75-28.99 μM) against various human tumor cell lines.
Full-text · Article · May 2012 · Journal of Natural Products
[Show abstract][Hide abstract] ABSTRACT: The antibacterial activity of two bisbenzylisoquinoline alkaloids, tetrandrine (Tet) and demethyltetrandrine (d-Tet), alone and in combination with the antibiotics ampicillin (AMP), azithromycin (AZM), cefazolin (CFZ) and levofloxacin (LEV) against 10 clinical isolates of staphylococcal chromosomal cassette mec (SCCmec) III type methicillin-resistant Staphylococcus aureus (MRSA) was studied. Susceptibility to each agent alone was tested using a broth microdilution method. The chequerboard and time-kill tests were used for the combined evaluations. The minimal inhibitory concentrations/minimal bactericidal concentrations (MICs/MBCs, μg/mL) ranges alone were 64-128/256-1,024 for both Tet and d-Tet. Significant synergies against 90% of the isolates were observed for the Tet/CFZ combination, with their MICs being reduced by 75-94% [fractional inhibitory concentration indices (FICIs) ranged from 0.188 to 0.625], respectively. An additive bactericidal result was also observed for the Tet (d-Tet)/CFZ combination in the time-kill experiments. These results demonstrated that Tet and d-Tet enhanced the in vitro inhibitory efficacy of CFZ. Their potential for combinatory therapy of patients infected with MRSA warrants further pharmacological investigation.