Antibacterial mechanism of chelerythrine isolated from root of Toddalia asiatica (Linn) Lam

BACKGROUND: Antimicrobial resistance was one of serious worldwide problems confused many researchers. To solve this problem, we explored the antibacterial effect of chelerythrine, a natural compound from traditional Chinese medicine and studied its action. METHODS: The contents of chelerythrine from different fractions of Toddalia asiatica (Linn) Lam (T. asiatica) were determined. The anti-bacterial activities of chelerythrine were tested by disc diffusion method (K-B method). Scanning electron microscopy (SEM), alkaline phosphatase (AKP), bacterial extracellular protein leakage and SDS-PAGE analysis were also used to investigate the antibacterial mechanism of chelerythrine. RESULTS: Analytic results of High Performance Liquid Chromatography showed that the content of chelerythrine (1.97 mg/g) in the ethyl acetate fraction was the highest, followed by those of methanol fraction and petroleum ether fraction. The in vitro anti-bacterial mechanisms of chelerythrine from T. asiatica were assessed. Chelerythrine showed strong antibacterial activities against Gram-positive bacteria, Staphylococcus aureus (SA), Methicillin-resistant S. aureus (MRSA), and extended spectrum β-lactamase S. aureus (ESBLs-SA). The minimum inhibitory concentrations (MICs) of chelerythrine on three bacteria were all 0.156 mg/mL. Furthermore, results suggested that the primary anti-bacterial mechanism of chelerythrine may be attributed to its destruction of the channels across the bacterial cell membranes, causing protein leakage to the outside of the cell, and to its inhibition on protein biosynthesis. Images of scanning electron microscope revealed severe morphological changes in chelerythrine-treated bacteria except control, damage of parts of the cell wall and cell membrane as well as the leakage of some substances. CONCLUSIONS: Chelerythrine isolated from root of Toddalia asiatica (Linn) Lam possesses antibacterial activities through destruction of bacterial cell wall and cell membrance and inhibition of protein biosynthesis.