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There are few effective medications to treat Alzheimer’s disease (AD). It has been suggested that several ginsenosides possess mild or moderate anti-AD activity. In our present work, a preferred combined ginsenosides was shown to have a more significant benefit effect on AD-like symptoms of worm paralysis and hypersensitivity to exogenous 5-HT in  C. elegans . The combined ginsenosides can suppress Aβ deposits and Aβ oligomers, alleviating the toxicity induced by Aβ overexpression more effectively than used alone. Its anti-AD effect was partially abolished by  hsf-1  RNAi knocked down or  hsf-1  inactivation by point mutation, but not by  daf-16  or  skn-1  RNAi knocked down. Furthermore, it markedly activated  hsp-16.2  gene expression downstream of HSF-1. Our results demonstrated that HSF-1 signaling pathway exerts an important role in mediating the therapeutic effect of combined ginsenosides on AD worms. These results provided powerful evidences and theoretical foundation for reshaping medicinal products of ginsenosides and ginseng on prevention of neurodegenerative diseases.

HSF-1 mediated combined ginsenosides ameliorating Alzheimer’s disease like symptoms in Caernorhabditis elegans