Natural products and phenotype directed screening in animal models have been prolific
fields for the discovery of innovative small molecule drugs – also in the field of
metabolic disease [1]–[2]. Since the screening of extracts and natural products (NP) in classical obesity
rodent models is hampered by several disadvantages, e.g. financial efforts, legal
and ethical considerations and the requirement of large quantities of test materials,
we established an obesity model in the nematode Caenorhabditis elegans (C. elegans). The C. elegans obesity assay is based on lipid staining of the mutant strain SS104 with the fluorescent
dye Nile Red. It can be performed with little sample amounts in 96-well plates with
medium throughput. An ethanolic extract of chaga, i.e. the fruit bodies of the mushroom
Inonotus obliquus (Ach. ex Pers.) Pilát, significantly inhibited the fat accumulation in C. elegans at 10 μg/mL, without having a negative effect on the nematodes’ lifespan and was
therefore selected for further mycochemical investigations. The extract was separated
via flash chromatography into 37 micro-fractions with quantitative variances of constituents
over several consecutive fractions. The effect on fat accumulation was determined
for each fraction and the increases and decreases of bioactivity were correlated with
the fractions’ 1H NMR spectra following a recently developed biochemometric approach named ELINA (Eliciting
Nature’s Activities) [3]. Together with UPC2-ELSD-QDa data we were able to pinpoint several constituents and their chemical features
responsible for the observed phenotypic effect, which enabled their targeted isolation.
