A novel pregnane-type alkaloid from Pachysandra terminalis inhibits methicillin-resistant Staphylococcus aureus in vitro and in vivo.

ABSTRACT

A new kind of pregnane-type alkaloid, 20α-dimethylamino-3ß-senecioylamino-16ß-hydroxy-pregn-5-ene (K-6), was isolated from Pachysandra terminalis Sieb. et Zucc., and its antibacterial activity against MRSA and MRSE was evaluated. We found that K-6 showed antibacterial effects against MRSA and MRSE with minimum inhibitory concentration values (25 mg/L), but did not induce antibiotic resistance in bacteria easily. The administration of K-6 dose-dependently improved the animal survival rate of mice infected with MRSA, with survival rates of 36.34% and 66.67% in the low-dose and high-dose groups, respectively. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. Scanning and transmission electron microscopy analyses indicated that the cytoplasm shrink of bacterial cells led to noticeable gaps between the cell membrane and cell cytoplasm, and the severely damaged cell membrane resulted in leakage of intracellular content, which ultimately caused the lethal effect of K-6 on bacteria. These findings demonstrated that K-6 is a potential agent against MRSA and MRSE.