Anti-neuroinflammation activity of acetylpuerarin mediated by a PKC-δ-dependent caspase signaling pathway: in vivo and in vitro studies.

Abstract

OBJECTIVE:

This study was performed to evaluate the regulating effects of acetylpuerarin on inflammation in an Alzheimer's disease (AD) rat model and an inflammatory cell model.

METHODS:

Healthy female Wistar rats and mouse BV2 microglia cells were selected. AD rat models were established with the method of bilateral intrahippocampal amyloid-β(Aβ)1-42 injections and the inflammatory cell models were established using Aβ25-35-induced mouse BV2 microglia cells. The cytotoxicity of acetylpuerarin on BV2 microglial cells was detected by MTT assay and the morphological changes of BV2 microglia cells were observed under inverted phase contrast microscope. As inflammatory parameters, the expressions of IL-1β, iNOS, IL-6 and TNF-α were examined by Elisa, Immunohistochemistry, Quantitative real-time PCR (qRT-PCR), Western blot and Immunofluorescence analyses. We also examined the acetylpuerarin's effect on the activity of PKC-δ, IKKβ and caspase-8/caspase-3 pathway.

RESULTS:

Acetylpuerarin exerted no significant cytotoxicity on BV2 microglia cells and was applied in all subsequent experiments. Acetylpuerarin treatment mitigated Aβ25-35-induced morphological changes associated with microglia activation. Moreover, the expressions of caspase-8, cleaved caspase-3, PKC-δ, IKKβ, iNOS, IL-1β and TNF-α in Aβ25-35-stimulated BV2 microglia cells were significantly suppressed by acetylpuerarin and in a dose-dependent manner. Additionally, the expression of IL-1β in hippocampus and the level of IL-6 in serum of Aβ1-42 treated rat were reduced by acetylpuerarin and in a concentration-dependent manner.

CONCLUSION:

Our results suggest that acetylpuerarin's anti-inflammation mechanism on AD may be mediated through the PKC-δ-dependent caspase signalling pathway.

• Authors: Q Y Cai, X L Liu, X Q Zhang, Y X Liu, M Li, C Z Zhao, X M Zhang, Q H Meng
• Journal: Die Pharmazie (Pharmazie) Vol. 71 Issue 10 Pg. 575-582 (Oct 01 2016) ISSN: 0031-7144 [Print] Germany
• PMID: 29441925 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Cytokines
• Isoflavones
• Peptide Fragments
• acetylpuerarin
• amyloid beta-protein (1-42)
• amyloid beta-protein (25-35)
• Prkcd protein, rat
• Protein Kinase C-delta
• Caspases

Topics

• Alzheimer Disease (chemically induced, drug therapy, pathology)
• Amyloid beta-Peptides
• Animals
• Caspases (drug effects)
• Cell Survival (drug effects)
• Cytokines (metabolism)
• Encephalitis (chemically induced, drug therapy)
• Female
• Isoflavones (pharmacology)
• Macrophage Activation (drug effects)
• Mice
• Microglia (drug effects)
• Peptide Fragments
• Protein Kinase C-delta (drug effects)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)