Identification of natural products with neuronal and metabolic benefits through autophagy induction

Yuying Fan, Nan Wang, Altea Rocchi, Weiran Zhang, Robert Vassar, Yifa Zhou, Congcong He

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Autophagy is a housekeeping lysosomal degradation pathway important for cellular survival, homeostasis and function. Various disease models have shown that upregulation of autophagy may be beneficial to combat disease pathogenesis. However, despite several recently reported small-molecule screens for synthetic autophagy inducers, natural chemicals of diverse structures and functions have not been included in the synthetic libraries, and characterization of their roles in autophagy has been lacking. To discover novel autophagy-regulating compounds and study their therapeutic mechanisms, we used analytic chemistry approaches to isolate natural phytochemicals from a reservoir of medicinal plants used in traditional remedies. From this pilot plant metabolite library, we identified several novel autophagy-inducing phytochemicals, including Rg2. Rg2 is a steroid glycoside chemical that activates autophagy in an AMPK-ULK1-dependent and MTOR-independent manner. Induction of autophagy by Rg2 enhances the clearance of protein aggregates in a cell-based model, improves cognitive behaviors in a mouse model of Alzheimer disease, and prevents high-fat diet-induced insulin resistance. Thus, we discovered a series of autophagy-inducing phytochemicals from medicinal plants, and found that one of the compounds Rg2 mediates metabolic and neurotrophic effects dependent on activation of the autophagy pathway. These findings may help explain how medicinal plants exert the therapeutic functions against metabolic diseases.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalAutophagy
DOIs
StateAccepted/In press - Nov 18 2016

Fingerprint

Autophagy
Biological Products
Phytochemicals
Medicinal Plants
Analytic Chemistry
Libraries
Housekeeping
AMP-Activated Protein Kinases
Metabolic Diseases
High Fat Diet
Glycosides
Insulin Resistance
Alzheimer Disease
Homeostasis
Up-Regulation
Steroids

Keywords

  • Alzheimer's disease
  • AMPK
  • amyloid
  • autophagy induction
  • ginsenoside
  • glycoconjugate
  • insulin resistance
  • medicinal plant
  • phytochemical

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Fan, Y., Wang, N., Rocchi, A., Zhang, W., Vassar, R., Zhou, Y., & He, C. (Accepted/In press). Identification of natural products with neuronal and metabolic benefits through autophagy induction. Autophagy, 1-16. https://doi.org/10.1080/15548627.2016.1240855

Identification of natural products with neuronal and metabolic benefits through autophagy induction. / Fan, Yuying; Wang, Nan; Rocchi, Altea; Zhang, Weiran; Vassar, Robert; Zhou, Yifa; He, Congcong.

In: Autophagy, 18.11.2016, p. 1-16.

Research output: Contribution to journalArticle

Fan, Yuying ; Wang, Nan ; Rocchi, Altea ; Zhang, Weiran ; Vassar, Robert ; Zhou, Yifa ; He, Congcong. / Identification of natural products with neuronal and metabolic benefits through autophagy induction. In: Autophagy. 2016 ; pp. 1-16.
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