Abstract

Background

: Tuberculosis is a very serious infectious disease that threatens humanity, and the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR) strains resistant to drugs suggests that new drug development is urgent. In order to develop new tuberculosis drug, we have conducted in vitro anti-tubercular tests on thousands of plant-derived substances and finally found collinin extracted from the leaves of Zanthoxylum schinifolium, which has an excellent anti-tuberculosis effect.

Purpose

: To isolate an anti-tubercular bioactive compound from the leaves of Z. schinifolium and evaluate whether this agent demonstrates any potential in vitro characteristics suitable for the development of future anti-tubercular drugs to treat MDR and XDR Mycobacterium tuberculosis.

Methods

: The methanolic extracts of the leaves of Z. schinifolium were subjected to bioassay-guided fractionation against M. tuberculosis using a microbial cell viability assay. In addition, following cell cytotoxicity assay, an intracellular anti-mycobacterial activity of the most active anti-tubercular compound was investigated after it was purified.

Results

: The active compound with anti-tubercular activity isolated from leaves of Z. schinifoliumwas identified as a collinin. The extracted collinin showed anti-tubercular activity against both drug-susceptible and -resistant strains of M. tuberculosis at 50% minimum inhibitory concentrations (MIC₅₀s) of 3.13-6.25 μg/ml in culture broth and MIC₅₀s of 6.25-12.50 μg/ml inside Raw264.7 and A549 cells. Collinin had no cytotoxicity against human lung pneumocytes up to a concentration of 100 μg/ml (selectivity index > 16-32).

Conclusions

: Collinin extracted from the leaves of Z. schinifolium significantly inhibits the growth of MDR and XDR M. tuberculosis in the culture broth. In addition, it also inhibits the growth of intracellular drug-susceptible and drug-resistant tuberculosis in Raw264.7 and A549 cells. To our knowledge, this is the first report on the in vitro anti-tubercular activity of collinin, and our data suggest collinin as a potential drug to treat drug-resistant tuberculosis. Further studies are warranted to assess the in vivo efficacy and therapeutic potential of collinin.