Mulberry leaf polyphenols delay aging and regulate fat metabolism via the germline signaling pathway in Caenorhabditis elegans

Mulberry leaves are an important ingredient in some traditional Chinese medicinal formulas and has been developed for use in functional food products. The antioxidant activity of mulberry leaf extract has been reported to have beneficial effects on diseases in vitro; however, it is not clear which components in mulberry leaf extracts have these functions. Furthermore, the mechanisms of action of these ingredients have not been extensively investigated. In this study, we extracted total mulberry leaf polyphenols (MLP) and identified its 13 phenolic monomers. Our results, using Caenorhabditis elegans as a model, indicated that MLPs delayed aging, improved oxidative stress resistance, and reduced fatty acid storage in vivo. Subsequent genetic screens and gene expression analyses demonstrated that the functions of MLP mainly depended on the germline signaling pathway, thus influencing the activities of downstream transcription factors (DAF-12, DAF-16, PHA-4, and NHR-80) as well as the expression levels of their target genes (fat-6, lipl-4, sod-3, unc-51, and fard-1). Our study determined that diverse modes of action on longevity were promoted by MLP exposure. These observations provide the first insight into MLP's multifaceted functions on aging, fat accumulation, and reproduction in vivo and indicate a specific model for the mechanism of action of MLP. This is a significant finding that lends support to the hypotheses that mulberry leaf extracts can have an impact on human health.