Sternberg PW, Ansell BRE, Andrews KT, Nowell C, Chang BCH, Hofmann A, Crawford S, Korhonen PK, Baell J, Gijs MAM, Fisher GM, Young ND, Preston S, Mouchiroud L, Gasser RB, Jabbar A, Auwerx J, Davis RA, McGee SL, Cornaglia M
[
FASEB J,
2017]
As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mito-ribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation.-Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee, S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E., Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W., Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain.
[
Plant Physiol Biochem,
2020]
The colorful petals of tree peony (Paeonia suffruticosa Andrews) are widely used as a source of additives in food, fragrances, and cosmetics. However, the nutritional composition of peony petals is undetermined, thereby limiting utility and product development. In this work, fresh petals of 15 traditional Chinese tree peony cultivars were selected to analyze the composition of soluble sugars, starch, and soluble protein. Extracted fatty acids (FAs) and flavonoids from petals were characterized by GC-MS and UPLC-triple-TOF-MS, respectively. The oxidative stress resistance (generated by paraquat) effects of petal extracts of three cultivars were also investigated in the model organism Caenorhabditis elegans. Our results showed that the petals were highly enriched in soluble sugars. 11 FAs were found in tree peony petals, and their compositions were similar to that of tree peony seeds. A total of 56 flavonoids were detected in tree peony petals, 28 of which were reported for the first time in tree peony petals, indicating that UPLC-triple-TOF-MS can improve the identification efficiency of flavonoids. Further analysis of tree peony petal metabolites indicated that anthocyanidin and flavonol composition might be used as specific chemotaxonomic biomarkers for cultivar classification. Flavonoids, linoleic acid, and -linolenic acid (ALA) in petals might provide antioxidant activity. 150mg/L of petal extracts of all three tested cultivars increased the lifespan of C. elegans. It was suggested that the petal extracts possessed anti-aging effects and oxidative stress resistance. These results highlight that tree peony petals can serve as natural antioxidant food resources in the future.