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

Abstract

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 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.

Influence of steeping time on biological activity of black mulberry leaves tea

“…It is well known that polyphenolic compounds exhibit wide range of biological activities such as antioxidant, antibacterial, anti-carcinogenic, anti-inflammatory, anti-viral, anti-allergic, estrogenic and immune-stimulating effects (3,(15)(16)(17). Furthermore, several studies also showed that the presence of polyphenolic compounds is very important because these compounds delay aging and regulate fat metabolism in Caenorhabditis elegans, which is used as a model (48) and lower hepatic lipid accumulation (49).…”

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…Many natural compounds with antioxidants that have anti-aging activity have been successfully tested in this model (Zheng et al 2014;Sonani et al 2014). This microscopic model system is preferred due to its short life cycle and transparent cuticle, which enables to monitor the physiological changes through a microscope.…”

Morus alba Accumulates Reactive Oxygen Species to Initiate Apoptosis via FOXO-Caspase 3-Dependent Pathway in Neuroblastoma Cells

“…The mulberry plant has been reported to be rich in flavonoids that have different biological activities, including its anti-oxidant capacity ( Zheng et al, 2014 ). In this study, MARE treatment of B103 cells was found to stimulate ROS accumulation and further depolarize the MMP.…”

“…Another study on leukaemia and melanoma showed that the water extract of mulberry root could disrupt the microtubule assembly of cancer cells; however, it could not arrest cells precisely at the G1 stage as taxol does ( Nam et al, 2002 ). Apart from the anticancer and anti-hyperglycaemic effects, one recent study pointed out that mulberry leaf polyphenols delayed the aging process and regulated fat metabolism in C. elegans ( Zheng et al, 2014 ). Mulberry also plays a protective role against different stresses; for example, it protects pancreatic β-cells from hydrogen peroxide via an anti-oxidant pathway ( Lee et al, 2014 ).…”