The protective effect of Epimedii Folium and Curculiginis Rhizoma on Alzheimer's disease by the inhibitions of NF-κB/MAPK pathway and NLRP3 inflammasome.

Zhou Lan,Ping Wang,Meng Wei,Lvyi Chen,Guangjing Xie

doi:10.18632/oncotarget.12574

Abstract

The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer’s disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test. The neuroprotective effect of EX were examined with methods of histochemistry and biochemistry. EX reduced the contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and cortex. EX also reduced the levels of malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px) in the serum. Immunohistochemical analysis demonstrated that EX inhibited the expressions of NLRP3. In addition, we further confirmed that EX suppressed the expression of the NLRP3 inflammasome. EX inhibited the phosphorylations MAPKs, nuclear factor κB (NF-κB), myeloid differentiation factor 88(MyD88), cathepsin B. In conclusion, these results suggest that EX may be a potential agent for treating Alzheimer’s disease.

Highlights

Alzheimer’s disease (AD), a common form of dementia, is a common neurogenerative disorder characterized by extracellular deposition of A beta (Aβ) plaques and intracellular accumulation of hyperphosphorylated tau protein and NFTs [1]
EX treatments (2 g/kg, 6 g/kg) significantly declined the production of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampus and cortex after intrahippocampal Aβ1-42 injection. These results demonstrated that EX might ameliorate Aβ1-42induced overproduction of pro-inflammatory cytokines, which was evidenced by the reverse effect of EX on the increase in the levels of IL-1β, IL-6 and TNF-α
Aβ1-42 is reported to be generated by www.impactjournals.com/oncotarget www.impactjournals.com/oncotarget successive cleavage of the amyloid precursor protein (APP) through β-secretase and γ-secretase [18], which was employed to induce AD to verify the effects of EX

Summary

Introduction

Alzheimer’s disease (AD), a common form of dementia, is a common neurogenerative disorder characterized by extracellular deposition of A beta (Aβ) plaques and intracellular accumulation of hyperphosphorylated tau protein and NFTs (neurofibrillary tangles) [1]. The progressive accumulation of Aβ into oligomers and plaques and the inter-neuronal NFTs contribute to synaptic loss, neuronal dysfunction and death within vulnerable brain regions, leading to the progressive loss of memory and executive functions [2]. There are more than 38 million AD patients in the worldwide and every four seconds a new patient is diagnosed with AD. This number is expected to double every 20 years and to reach 115 million in 2050 due to the increasing aging population [3]. The effective treatment of AD becomes more urgent and remains a challenge

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