Isolation of natural products with anti-ageing activity from the fruits of Platanus orientalis

Background: Ageing is defined as the time-dependent decline of functional capacity and stress resistance resulting in increased morbidity and mortality. Hypothesis/Purpose: Reportedly, these effects can be delayed by mild genetic or pharmacological activation of the main modules of the proteostasis network. Study Design-Methods: By employing advanced phytochemical methods we isolated natural products from the fruits of Platanus orientalis and studied (via a bio-guided approach) their effects in Drosophila flies, as well as in normal human fibroblasts. Results: We report herein that dietary administration in Drosophila flies of a phenolics-enriched methanol extract from the fruits of Platanus orientalis exerted antioxidant effects; activated proteostatic mechanisms and mildly extended flies' longevity. We then isolated the two major compounds of the extract, namely Platanoside and Tiliroside and found that enrichment of the total extract with these compounds decreased oxidative stress and (in the case of the Tiliroside enriched extract) activated proteostatic mechanisms. Administration of purified Tiliroside in flies activated proteostatic genes, enhanced proteasome and lysosomal-cathepsin activities and decreased tissues' oxidative load; moreover, it delayed the rate of age-related decrease in flies' locomotion activity and increased flies' longevity. Notably, Tiliroside also activated proteasome in normal human fibroblasts and delayed progression of cellular senescence indicating that it may also impact on human cells rate of senescence. Conclusion: Our presented findings highlight the potential anti-ageing activity of naturals products derived from the fruits of P. orientalis.