The genotoxicity and cytotoxicity assessments of andrographolide in vitro

Andrographolide is a major phytoconstituent present in Andrographis paniculata, a plant used in traditional medicines in Asia for various ailments. This tropical shrub was reported to possess various pharmacological activities and has been marketed around the world including Europe, however the toxicological data especially potential genotoxicity assessment on the phytocompound is still lacking. This study was performed to assess the ability of andrographolide to induce chromosomal changes using the in vitro cytokinesis-blocked micronucleus assay with immunofluorescent labelling of kinetochores in metabolically-competent AHH-1 and MCL-5 human lymphoblastoid cell lines. Various cytotoxicity endpoints were also evaluated in this study. Andrographolide was found to cause a weak increase in micronuclei induction at 10-50 μM in both AHH-1 and MCL-5 cell lines, respectively which were within the historical range. Kinetochore analysis revealed that the micronuclei induced in MCL-5 cells due to andrographolide exposure originated via an aneugenic mechanism that was indicated by the relatively higher but non-significant percentage of kinetochore positive micronuclei compared to negative control. Andrographolide also elicited a dose-dependent cellular cytotoxicity, with cells dying primarily via necrosis compared to apoptosis. Here we report that andrographolide was not genotoxic at the doses tested and it induces dose-dependent necrosis in vitro.