Hylocereus undatus extends lifespan and exerts neuroprotection in Caenorhabditis elegans via DAF-16 mediated pathway

BACKGROUND: Hylocereus undatus is a traditional medicinal plant known for its medicinal, nutritional and commercial uses. OBJECTIVE: To address the anti-aging and neuroprotective efficacies of fruit peel extracts of H. undatus using Caenorhabditis elegans model. METHODS: C. elegans (wild-type (N2), transgenic and mutant strains) were treated with H. undatus and monitored for lifespan and neuroprotection through physiological assays, fluorescence microscopy and qPCR analysis. LC-MS/MS analysis was performed to identify the phytochemicals present in the extract. Molecular docking studies were employed to identify the interaction mode of selected phytochemicals with Aβ, DAF-16 and SKN-1. RESULTS: The extract was able to extend the lifespan of C. elegans (N2), extend the lifespan and reduce paralysis of Aβ transgenic strains CL2006 and CL4176, suggesting its anti-aging and neuroprotective potential. The LC-MS/MS analysis revealed the presence of phytochemicals including homostachydrine, betaine, syringic acid, typhaneoside, rutin, and behenic acid. The extract could activate antioxidant mechanism, through SKN-1, which was evident in qPCR and transgenic strain LG333. These effects were mediated through DAF-16 pathway as the extract was able to upregulate the expression of daf-16 in N2, increase the nuclear localization of daf-16 in transgenic strain TJ356, and not able to significantly alter the lifespan of both DAF-2 and DAF-16 mutants, CB1370 and CF1038 respectively. Finally, in molecular docking approach, typhaneoside and rutin showed better binding affinity with SKN-1 and DAF-16 when compared to resveratrol and similar binding affinity with Aβ when compared to donepezil. CONCLUSION: Taken together, this study indicates that H. undatus activates anti-aging and neuroprotection via DAF-16 mediated pathway.