The value of in vitro cytotoxicity testing in identifying suitable plant-based preparations for use in animal healthcare

Searching for bioactive chemicals in plant extracts for development into animal health products is a fruitful area of research, reflected by increasing global interest. As with human medications, investigation of potential toxic effects at an early stage is required to exclude less promising candidates. The mechanism of action of most toxic chemicals is associated with basic biochemical processes common to all cells, and correlations exist between toxic concentrations determined in vitro to those noted in vivo.

Many parameters need to be taken into account when assessing toxicity of plant extracts and compounds. Limitations of cytotoxicity tests include difficulties in extrapolating results to in vivo situations where pharmacokinetic aspects, particularly metabolism, play a role. For mixtures like plant extracts it is challenging to predict interactions between different components as well as varying degrees of bioavailability.

Biological efficacy is generally not due to cytotoxicity when the selectivity index (SI, ratio of cytotoxicity to biological activity) is greater than or equal to 10. In antimicrobial and anthelmintic investigations of plant extracts in our research group, SI values are used to highlight active extracts with low toxicity, and also those selectively active against certain test organisms. This provides good leads for continuing research on promising extracts that may be sources of interesting biologically active and therapeutically useful preparations with excellent activity and low toxicity. For example, research in our group has led to identification of plant extracts and compounds that inhibit the hatching of eggs and development of larvae of Haemonchus strongyloides, one of the most important nematodes affecting sheep production in the world. In another example to be discussed, a crude leaf extract of Loxostylus alata had the same antifungal efficacy as amphotericin B in lungs of chicks infected with Aspergillus fumigatus.