Tanshinone I inhibited growth of human chronic myeloid leukemia cells via JNK/ERK mediated apoptotic pathways

Tanshinone I (Tan I) is one of the main bioactive ingredients derived from Salvia miltiorrhiza Bunge, which has exhibited antitumor activities toward various human cancer cells. However, its effects and underlying mechanisms on human chronic myeloid leukemia (CML) cells still require further investigation. This study determined the effects and mechanisms of anti-proliferative and apoptosis induction activity induced by Tan I against K562 cells. The cytotoxic effect of Tan I at varying concentrations on K562 cells was evaluated via MTT assay. Cell apoptosis was further investigated through DAPI staining and flow cytometry analysis. The expression levels of apoptosis-related proteins and activities of JNK/ATF2 and ERK signaling pathways were analyzed by western blot. Quantitative PCR was performed to further determine mRNA expression levels of JNK1/2 and ERK1/2 after Tan I treatment. The results indicated that Tan I significantly inhibited K562 cell growth and induced apoptosis in a concentration- and time-dependent manner. It induced significant cellular morphological changes and increased apoptosis rates in CML cells. Tan I promoted the cleavages of caspase-related proteins, as well as increased the expression levels of PUMA. Furthermore, Tan I significantly activated JNK and inhibited ATF-2 and ERK signaling pathways. The mRNA expression levels of JNK1/2 and ERK1/2 were up-regulated by Tan I, further confirming its regulatory effects on JNK/ERK signaling pathways. Overall, our results indicated that Tan I suppressed cell viability via JNK- and ERK-mediated apoptotic pathways in K562 cells, suggesting that it might be a promising candidate as a novel anti-leukemia drug.

Mitigating effect of tanshinone IIA on ventricular remodeling in rats with pressure overload-induced heart failure

Abstract Purpose To investigate the effect of tanshinone IIA (TIIA) on ventricular remodeling in rats with pressure overload-induced heart failure. Methods Pressure overload-induced heart failure model (abdominal aortic coarctation) was established in 40 rats, which were divided into model and 5, 10 and 20 mg/kg TIIA groups. Ten rats receiving laparotomy excepting abdominal aortic coarctation were enrolled in sham-operated group. The 5, 10 and 20 mg/kg TIIA groups were treated with 5, 10 and 20 mg/kg TIIA, respectively, for 8 weeks. Results Compared with model group, in 20 mg/kg TIIA group the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, ±maximum left ventricular pressure rising and dropping rate, and myocardial B-cell lymphoma-2 and cleaved cysteinyl aspartate specific proteinase-3 protein levels were increased, respectively (P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic pressure, heart weight index, left ventricular weight index, serum B-type brain natriuretic peptide, interleukin 6 and C-reactive protein levels and myocardial B-cell lymphoma-2 associated X protein level were decreased, respectively (P<0.05). Conclusion TIIA may alleviate ventricular remodeling in rats with pressure overload-induced heart failure heart by reducing inflammatory response and cardiomyocyte apoptosis.

Antibacterial potential of non-volatile constituents of Rosmarinus officinalis against 37 clinical isolates of multidrug-resistant bacteria / Actividad antibacteriana de constituyentes no volátiles de Rosmarinus officinalis contra 37 aislamientos clínicos de bacterias multirresistentes

In this paper we investigated the antibacterial activity of a methanolic extract of Rosmarinus officinalis L. and their main constituents, carnosic acid and rosmarinic acid, against 37 nosocomial strains of multidrug-resistant bacteria. Results obtained showed that both the rosemary extract and carnosic acid inhibited all clinical isolates of Staphylococcus aureus methicillin-resistant and Enterococcus faecalis gentamicin and streptomycin-resistant bacteria examined (MICs 60 ug/mL vs. 200 ug/mL, respectively). Rosemary extract showed MIC values between 400 and 1600 ug/ml against the Gram-negative multidrug-resistant bacteria: Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Morganella morganii and Providencia stuartii, while carnosic acid showed MIC of 120 to 240 ug/mL. Bactericidal effect of carnosic acid against S. aureus and E. faecalis was observed at their MIC value, while 2 x MIC to 4 x MIC were needed to kill Gram-negative bacteria. Rosmarinic acid showed a narrow spectrum of action against a few Gram-negative clinical isolates. Our findings suggest that carnosic acid would be a good lead candidate useful in counteracting drug-resistant infections.

En este trabajo evaluamos la actividad antibacteriana de un extracto metanólico de Rosmarinus officinalis L. y sus principales componentes el ácido carnósico y ácido rosmarínico, contra 37 cepas de bacterias multirresistentes nosocomiales. Los resultados muestran que el extracto de romero y el ácido carnósico, inhibieron las bacterias Gram-positivas Staphylococcus aureus resistentes a meticilina y Enterococcus faecalis resistentes a gentamicina y estreptomicina (CIM 200 ug/mL y 60 ug/mL, respectivamente). El extracto de romero inhibió los Gram negativos multirresistentes: Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, Morganella morganii y Providencia stuartii (CIM 400 a 1600 ug/mL), mientras que el ácido carnósico mostró valores de CIM entre 120 a 240 ug/mL. El ácido carnósico mostró actividad bactericida contra S. aureus y E. faecalis a su CIM, mientras que 2 a 4 X CIM se requirieron para matar las bacterias Gram-negativas. El ácido rosmarínico mostró inhibió unos pocos aislados clínicos Gram-negativos. Estos hallazgos sugieren que el ácido carnósico puede ser de utilidad contra infecciones bacterianas multirresistentes a antibióticos.