Integration of semi-automatic tools for assessing health promoting effects of natural products in C.elegans

The average life expectancy of the human population is constantly increasing. According to the WHO, the number of people aged 80 years or older will be tripled by the year 2050. Ageing itself is associated with the constant impairment of the general health status and the occurrence of age-related diseases [1]. As a multipurpose tool for the identification of health promoting agents from nature, this study aims to identify herbal and fungal natural products (NPs) able to decelerate the ageing process and to attenuate ageing- related diseases (e.g. neurodegenerative disorders or metabolic disorders). We therefore used the model organism Caenorhabditis elegans in a previously established phenotypic screening platform with liquid cultures in a 96-well plate format adapted to small scale extract screenings [2] [3]. Hit extracts selected based on their health-promoting phenotypic readouts are dereplicated by LC-MS/MS based chemical profiling. Bioactive constituents and their molecular mechanism will be identified using in silico predictions and target-oriented assays. To further improve and accelerate the screening of NPs in nematodes, we applied a semiautomatic IR-based wormtracker and optimized its methodological parameters in various C. elegans assays focusing on lifespan, health span and neurodegenerative disorders. The comparison of results obtained from probing 70 herbal and fungal extracts by means of timeconsuming counting techniques with those from the semi-automated screening proved the robustness and suitability of the wormtracker as a valuable tool for NP screenings with medium and high throughput.

Funding Schwabe Phyto Innovation Challenge 2022 by Dr Willmar Schwabe GmbH & Co. KG

 

MissingLinkText

Conflict of Interest

The authors declare no conflict of interest.

• References

• 1 World Health Organization. Ageing and health. 2021 [cited 21.09.2022]; Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health.
• 2 Kirchweger B., Klein-Junior L.C., Pretsch D., Chen Y., Cretton S., Gasper A.L., Vander Heyden Y., Christen P., Kirchmair J., Henriques A.T.. Azepine-lndole Alkaloids From Psychotria nemorosa Modulate 5-HT2a Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans, Frontiers in neuroscience 2022; 16: 826289
• 3 Zwirchmayr J., Kirchweger B., Lehner T., Tahir A., Pretsch D., Rollinger J.M.. A robust and miniaturized screening platform to study natural products affecting metabolism and survival in Caenorhabditis elegans. Scientific reports 2020; 10 (01) 1-12

Publication History

Article published online:
16 November 2023