Caenorhabditis elegans as model to study natural products affecting metabolism and lifespan

Current drug discovery efforts are mainly focused on target directed approaches, which have certain limitations owing to the complexities of biological systems and disease pathophysiology. Still a major part of new drug entities is discovered by phenotype directed approaches in cells and animals [1]. The screening of natural products in phenotypic rodent models is however hampered by several disadvantages, e.g. financial efforts, legal and ethical considerations, large quantities of test materials, in particular pure isolates and a challenging target deconvolution afterwards. Many of these problems can be avoided by using the simple roundworm Caenorhabditis elegans which serves as a convenient and proficient addition to the set of current preclinical model organisms [2]. We recently established a robust C. elegans screening platform using 96-well plates for medium throughput screening of extracts and constituents thereof for the discovery of natural products beneficial to the metabolic syndrome. Herein we present approaches and methods for C. elegans based preclinical screening using a combination of (i) optimized extract preparation, (ii) lifespan assay and (iii) fat accumulation assay.

• References

• 1 Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discovery 2011; 10: 507-519.
• 2 O’Reilly LP. et al. C. elegans in High-Throughput Drug Discovery. Adv Drug Delivery Rev 2014; 0: 247-253.