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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.

Vasculopathy including endothelial cell (EC) apoptosis and inflammation contributes to the high incidence of stroke and myocardial infarction in diabetic patients. The aim of the present study was to investigate the effect of calycosin-7-O-β-D-glucopyranoside (CG), a phytoestrogen, on advanced glycation end products (AGEs)-induced HUVEC damage. We observed that CG can significantly ameliorate AGEs-induced HUVEC oxidative stress and apoptosis. The ratio of SOD/MDA was significantly increased to the normal level by CG pretreatment. CG preincubation dramatically increased anti-apoptotic Bcl-2 while decreased pro-apoptotic Bax and Bad expressions as detected by immunocytochemistry. Moreover, CG ameliorated macrophage migration and adhesion to HUVEC; the monocyte chemotactic protein-1 and interleukin-6 levels in the culture supernatant were dramatically reduced by CG as determined by ELISA; the expressions of inflammatory proteins including ICAM-1, TGF-β1, and RAGE in both protein and mRNA levels were significantly reduced to the normal level by CG pretreatment as determined by immunocytochemistry and real-time RT-PCR. The intracellular investigation suggests that CG can reverse AGEs-activated ERK1/2 and NF-κB phosphorylation, in which estrogen receptors were involved in. Our results strongly indicate that CG can modulate EC dysfunction by ameliorating AGEs-induced cell apoptosis and inflammation.

Ethnopharmacological relevance Traditional herbs are a valuable source of novel antibacterials in combating pathogenic isolates of methicillin-resistant Staphylococcus aureus (MRSA), a global nosocomial problem. Aim of the study To assess in vitro anti-MRSA activity of extracts from Chinese herbs. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined in the setting of clinical MRSA isolates. Materials and methods A collection of 19 plant extracts were obtained and bioassay-guided phytochemical analysis performed. Antibacterial susceptibilities were screened for inhibitory zone and MICs/MBCs determined by serial dilution with a standardized microdilution broth methodology. 9 MRSA isolates and a standard control strain (ATCC 25923) were cultured and exposed to the plant extract and isolated compound. Vancomycin was used as a positive control agent. Results All the presented 19 plants showed anti-MRSA activity with MIC of 1.25–3.07 mg/ml. The most active antimicrobial plants were Dendrobenthamia capitata , Elsholtzia rugulosa , Elsholtzia blanda , Geranium strictipes and Polygonum multiflorum (MIC ≤ 1.43 mg/ml), and betulinic acid isolated from the active ethyl acetate fraction of Dendrobenthamia capitata extract was determined with MIC/MBC values as 62.5/125.0 mg/ml. Conclusions Dendrobenthamia capitata , Elsholtzia rugulosa , Elsholtzia blanda , Geranium strictipes Polygonum multiflorum and betulinic acid demonstrate promising anti-MRSA potential.

Treatment of the chronic hepatitis C virus (HCV) infection is an unmet medical need, and the HCV NS3 serine protease (NS3-SP) has been used as an attractive target of antiviral screening against HCV. To find naturally chemical entities as lead compounds from which novel anti-HCV agents could be developed, bioassay-guided fractionation and isolation were performed on a crude ethanol extract from rhizomes of the Chinese medicinal herb Rhodiola kirilowii (Regel) Maxim using column chromatography (CC) techniques and in vitro inhibitory activity against HCV NS3-SP. The partition of the extract between water and different organic solvents led to the isolation and identification of 12 compounds in the ethyl acetate part which proved to be the most active. These compounds were tested for in vitro activity against HCV NS3-SP, among which four (-)-Epicatechin derivatives: 3,3'-Digalloylproprodelphinidin B2 (Rhodisin, 1); 3,3'-Digalloylprocyanidin B2 (2); (-)-Epigallocatechin-3-O-gallate (EGCG, 3); and (-)-Epicatechin-3-O-gallate (4, ECG) represented the most potent ones with IC(50) of 0.77, 0.91, 8.51, and 18.55 microM, respectively. Salidroside, the commonly known compounds, together with the other compounds showed no activity up to 100.0 microM. Methylation and acylation of the hydroxyl groups of 1-4 caused a decrease of activity. Cell viability and secreted alkaline phosphatase (SEAP) activity assays with 1-4 revealed little if any toxicity. These nonpeptide inhibitors of HCV NS3-SP might serve as potential candidate anti-HCV agents.

The aim of this study was to search for new natural anti-HCV agents from Chinese herbal medicine. Bioactivity-guided extraction and isolation methods were used. Active part and pure compounds were obtained from ethanolic extract of Saxifraga melanocentra Franch. and their in vitro inhibitory activities (IC50) against HCV NS3 serine protease were tested by enzyme-linked immunosorbent assay. Results showed that the polyphenolic ethyl acetate part of the herbal extract was the most active, and from this 18 polyphenols representing active compounds were isolated and identified. IC50 values of these compounds and five related ones were obtained. A broad-degree of anti-HCV activity was observed among them in the following order: gallated esters of D-glucose and rutin (0.68–4.86 μM)> flavonoids (33.11–370.37 μM)> gallic acid and its methyl and ethyl esters, Bergenin and others (over 1000 μM). The most active compound was 1,2,3,4,6-penta- O-galloyl-β-D-glucoside (0.68 μM). In conclusion, polyphenols were responsible for the anti-HCV constitution of S. melanocentra, and multigallated esters of D-glucose possessed the strongest inhibition against HCV NS3 serine protease and little cytotoxic effect, suggesting the potential use of these compounds for designing and developing drugs for treatment of the viral infection.

Ethnopharmacological relevance The herb of Chelidonium majus Linn is known to possess a variety of biological activities and applied in the therapy of various infectious diseases. Aim of the study To evaluate the in vitro antifungal activity of the active components from Chelidonium majus against clinical drug-resistant yeast isolates. Materials and methods Active compounds were obtained using bioassay-guided method. Six species of yeast fungi were exposed to the compounds. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined according to the standard broth microdilution method. Results Of the six compounds determined, 8-hydroxydihydrosanguinarine ( 1 ) and 8-hydroxydihydrochelerythrine ( 2 ) demonstrated potent activity with the MIC ranges of 2–80 and 4–100 μg/mL, respectively. Dihydrosanguinarine ( 3 ), dihydrochelerythrine ( 4 ), sanguinarine (5) and chelerythrine (6) had some degree of antifungal activity. Conclusions The overall results provided important information for the potential application of the 8-hydroxylated alkaloids from Chelidonium majus in the therapy of serious infection caused by drug-resistant fungi.

Two new atisane-type diterpenoid glucosides, spiraeosides A (1) and B (2), were isolated from the aerial parts of Spiraea japonica L. f. var. ovalifolia. Their structures were characterized based on spectral analysis, and the structure of 1 was further confirmed by single-crystal X-ray diffraction.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 microM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells., published_or_final_version