, 36:9719 | Cite as

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

  • Shanqing ZhengEmail author
  • Sentai LiaoEmail author
  • Yuxiao Zou
  • Zhi Qu
  • Weizhi Shen
  • Ying Shi


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.


Mulberry leaf polyphenols Caenorhabditis elegans Germline signaling pathway Transcription factors Aging Fat metabolism 



Mulberry leaf polyphenols

C. elegans

Caenorhabditis elegans


Dauer formation protein 16


Dauer formation protein 12


Forkhead box protein O


a FOXA transcription factor


Nuclear hormone receptor 80


Insulin/IGF-1 like signaling pathway


Skinhead, a homolog of mammalian Nrf proteins


Wild-type C. elegans



We thank the Caenorhabditis Genetics Center (CGC), which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440), and Dr. Luo from Kunming Institute of Botany, Chinese Academy of Sciences, for providing all the worm strains. This work was supported by the Special Fund for Agro-scientific Research in the Public Interest (201403064) and the Nation Key Technology R&D Program (2012BAD36B07).

Supplementary material

11357_2014_9719_MOESM1_ESM.doc (275 kb)
ESM 1 (DOC 275 kb)


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Copyright information

© American Aging Association 2014

Authors and Affiliations

  1. 1.Sericulture and Agri-Food Research InstituteGuangdong Academy of Agricultural SciencesGuangzhouChina

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