Suppression of MIF-induced neuronal apoptosis may underlie the therapeutic effects of effective components of Fufang Danshen in the treatment of Alzheimer's disease

Acta Pharmacologica Sinica
Cheng-Jie LiangJie Yang

Abstract

Fufang Danshen (FFDS or Compound Danshen) consists of three Chinese herbs Danshen (Salviae miltiorrhizae radix et rhizome), Sanqi (Notoginseng radix et rhizome) and Tianranbingpian (Borneolum, or D-borneol), which has been show to significantly improve the function of the nervous system and brain metabolism. In this study we explored the possible mechanisms underlying the therapeutic effects of the combination of the effective components of FFDS (Tan IIA, NG-R1 and Borneol) in the treatment of Alzheimer's disease (AD) based on network pharmacology. We firstly constructed AD-related FFDS component protein interaction networks, and revealed that macrophage migration inhibitory factor (MIF) might regulate neuronal apoptosis through Bad in the progression of AD. Then we investigated the apoptosis-inducing effects of MIF and the impact of the effective components of FFDS in human neuroblastoma SH-SY5Y cells. We observed the characteristics of a "Pendular state" of MIF, where MIF (8 ng/mL) increased the ratio of p-Bad/Bad by activating Akt and the IKKα/β signaling pathway to assure cell survival, whereas MIF (50 ng/mL) up-regulated the expression of Bad to trigger apoptosis of SH-SY5Y cells. MIF displayed neurotoxicity similar to Aβ1...Continue Reading

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Citations

Jan 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Cristina PetraliaMaria Sofia Basile
Sep 29, 2020·Neural Regeneration Research·Kenneth Maiese
Jun 22, 2021·Bioorganic & Medicinal Chemistry·Helmut M HügelAnthony Lingham

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Methods Mentioned

BETA
protein assay
flow cytometry
ELISA
light microscopy
ubiquitination

Software Mentioned

Graph Pad
Cytoscape
Analyzer Network
XFluor4
Studio
ImageJ
BD Accuri CFlow
Discovery
IntAct
Graph Pad Prism

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