Abstract
Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE in Caenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan of C. elegans by 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components, daf-2 and age-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan of C. elegans through the IIS and SKN-1/Nrf2 signaling pathways.
Highlights
Oleuropein (OLE), a bitterness substance belonging to secoiridoid, is the major bioactive compound in Oleaceae plants (Figure 1a)
To further confirm whether OLE mediated the healthspan via the insulin/IGF-1 signaling (IIS) p the beneficial effect of OLE on the IIS pathway-related null mutants was investig shown in Figure 9 and Table S3, OLE did not affect the lifespan of daf-2, age-1, sg daf-16 null mutants compared to the control group
OLE treatment promoted the migration of DAF-16 into the nucleus, which induced the activities and expressions of antioxidant enzymes, including sod-3, ctl-1, and ctl-2
Summary
Oleuropein (OLE), a bitterness substance belonging to secoiridoid, is the major bioactive compound in Oleaceae plants (Figure 1a). In addition to DAF-16, some other transcription creasing the transcriptional regulation of DAF-16 on downstream targeted genes to extend factors are by IIS, such as SKN-1, an Nrf transcription that the lifespan andregulated enhance stress resistance. Part of SKN-1/Nrf downstream targets factors are regulated by IIS, such as SKN-1, an Nrf transcription factor homolog that overlaps with targeted genes involvedPart in the of lifespan extension and regulates both DAF-16 longevity and stress response. Study was aimed to evaluate the stress resistance and lifespan extension stressThe responses effect of OLE using C. elegans as in vivo model. For those purposes, the survival rates of.
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