Longevity-promoting effects of 4-hydroxy-E-globularinin in Caenorhabditis elegans

In modern times, there has been a major increase in the use of plants or herbal constituents for the prevention of age-related disorders. 4-Hydroxy-E-globularinin (4-HEG) is an iridoid and a major component of Premna integrifolia. This investigation represents a breakthrough in geriatrics by showing the longevity-promoting activity of 4-HEG in the animal model Caenorhabditis elegans. 4-HEG (20μM) enhanced the mean life span of worms by over 18.8% under normal culture conditions and also enhanced their survival under oxidative stress. The longevity-promoting activity was associated with reduced reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies verified the role of ROS detoxification pathways and simultaneous nuclear translocation of DAF-16 in the 4-HEG-mediated effects. Quantitative real-time PCR estimations and observations of transcriptional reporters indicated that 4-HEG was able to upregulate stress-inducible genes, viz., hsp-16.2 and sod-3. Thus, 4-HEG may serve as a lead compound of plant origin for the development of important nutraceuticals superseding the aging process. [Display omitted] ► 4-Hydroxy-E-globularinin (4-HEG) is a natural molecule isolated from the medicinal plant Premna integrifolia. ► We examined the life span of wild-type N2 Caenorhabditis elegans and daf-16, sir-2.1, and mev-1 mutants. ► 4-HEG reduced reactive oxygen species levels and fat accumulation in the worms. ► 4-HEG extended the life span of worms via DAF-16 activation.