Cinnamic aldehyde, isolated from Cinnamomum cassia, alone and in combination with pyrazinamide against Mycobacterium tuberculosis in vitro and in vivo

Abstract

Pyrazinamide (PZA)-resistant Mycobacterium tuberculosis has gradually increased in recent years. Therefore, the discovery of drugs that can enhance the effect of PZA has important value in the treatment of tuberculosis. Cinnamomum cassia Blume (Lauraceae) is popularly used in China and Africa to treat gastritis, chronic bronchitis, diabetes and other diseases. The aims of this study were to isolate molecules with anti-Mtb activity from the extract of twig of C. cassia and evaluate the active molecule alone or in combination with PZA against Mycobacterium tuberculosis in vitro and in vivo. Compound 1, with anti-Mycobacterium tuberculosis activity (MIC = 10 μg/ml), was isolated from the extract of twig of C. cassia using bioassay-guided approach, and identified as cinnamic aldehyde on the basis of its spectroscopic data. The MICs of compound 1 against E. coli, S. aureus, and M. tuberculosis were 640, 320, and 10 μg/ml, respectively. The compound 1 in combination with PZA showed additive effect (FICI: 0.75). Compound 1 showed no toxicity on the growth of Vero cells at concentration of 120 μg/ml. Its selectivity index (SI) was 12. The in vivo experiment showed that compound 1 and PZA clearly act synergistically against Mycobacterium tuberculosis in the murine model. Scanning electron microscopy showed that M. tuberculosis cells swelled, collapsed and ruptured after treatment with sub-inhibitory concentration of compound 1. This implies that the anti-M. tuberculosis mechanism of compound 1 might be associated with disruption of cell wall. The above results indicate that compound 1 could be used as a drug candidate in new regimens design for TB treatment.