Abstract
Flavonoids are potential nutraceutical compounds present in diary food. They are considered health-promoting compounds and promising drugs for different diseases, such as neurological and inflammatory diseases, diabetes and cancer. Therefore, toxicological and mechanistic studies should be done to assert the biological effects and identify the molecular targets of these compounds. In this work we describe the effects of six structurally-related flavonoids—baicalein, chrysin, scutellarein, 6-hydroxyflavone, 6,7-dihydroxyflavone and 7,8-dihydroxyflavone—on Caenorhabditis elegans’ lifespan and stress resistance. The results showed that chrysin, 6-hydroxyflavone and baicalein prolonged C. elegans’ lifespan by up to 8.5%, 11.8% and 18.6%, respectively. The lifespan extensions caused by these flavonoids are dependent on different signaling pathways. The results suggested that chrysin’s effects are dependent on the insulin signaling pathway via DAF-16/FOXO. Baicalein and 6-hydroxyflavone’s effects are dependent on the SKN-1/Nfr2 pathway. In addition, microarray analysis showed that baicalein downregulates important age-related genes, such as mTOR and PARP.
Highlights
Flavonoids are low-molecular-weight polyphenols present in plants that have been consumed for ages, as they are found in several foods of plant origin, such as cocoa, tea, fruits and wine
This strain presented the HSP16.2 fused with the green fluorescent protein GFP, and it was located in the pharynx
Microarray testing was performed for worms treated with baicalein at the highest concentration measured (i.e., 100 μM) and the results show how even though the lifespan extension at 100 μM was low, the effects of the flavonoid baicalein on C. elegans may be partially related to the downregulation of the expression of mTOR, which produces a lifespan extension dependent on SKN-1, this being the same effect reported in worms treated with rapamycin [39]
Summary
Flavonoids are low-molecular-weight polyphenols present in plants that have been consumed for ages, as they are found in several foods of plant origin, such as cocoa, tea, fruits and wine. Around 8000 flavonoid-like structures have been identified [1]. Flavonoids are considered health-promoting and disease-preventing compounds, since they are associated with several positive effects related to their antioxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities [3]. They are potent inhibitors of some key enzymes, such as cyclo-oxygenase (COX) [4] and lipoxygenase (LOX) [5] and possible candidates in neurodegenerative disease treatments (Alzheimer’s and Parkinson’s treatments) [6,7]
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