Original Research ARTICLE
Bee venom soluble phospholipase A2 exerts neuroprotective effects in a lipopolysaccharide-induced mouse model of Alzheimer’s disease via inhibition of nuclear factor-kappa B
- 1Chungbuk National University, South Korea
- 2Other, South Korea
Neuroinflammation is important in the pathogenesis and development of Alzheimer’s disease (AD). In the AD brain, microglial activation and upregulation of pro-inflammatory mediators both induce amyloid beta (Aβ) accumulation. Regulatory T cells (Tregs) and nuclear factor-kappa B (NF-κB) signaling have been implicated in AD development through their effects on neuroinflammation and microglial activation. The bee venom soluble phospholipase A2 (bv-sPLA2) enzyme is known to exert anti-inflammatory and anti-immune effects. Here, we investigated the inhibitory effects of bv-sPLA2 on memory deficiency in a lipopolysaccharide (LPS)-induced mouse model of AD. We examined whether bv-sPLA2 (0.02, 0.2, and 2 mg/kg by i.p. injection 3 times for 1 week) could inhibit neuroinflammation and memory impairment in LPS-treated mice (250 μg/kg by i.p. injection daily for 1 week). We also assessed the effects of bv-sPLA2 administration (0.01, 0.1, and 1 μg/mL) on LPS (1 μg/mL)-treated microglial BV-2 cells. In the LPS-injected mouse brain, sPLA2 treatment rescued memory dysfunction and decreased Aβ levels through the downregulation of amyloidogenic proteins and decreased the expression of inflammatory proteins and pro-inflammatory cytokines. Moreover, the LPS-mediated increase in inflammatory protein expression was attenuated bv-sPLA2 treatment in BV-2 cells. Treatment with bv-sPLA2 also downregulated signaling by NF-κB that is considered an important factor in the regulation of neuroinflammatory and amyloidogenic responses, both in vivo and in vitro. Additionally, co-treatment with NF-κB (5 μM) and bv-sPLA2 (0.1 μg/mL) exerted more marked anti-inflammatory effects compared to sPLA2 treatment alone. These results indicate that bv-sPLA2 inhibits LPS-induced neuroinflammation and amyloidogenesis via inhibition of NF-κB.
Keywords: Neuroinflammation, Alzheimer’s disease, NF-κB – Nuclear factor kappa B, Regulatory T cells (T reg), bee venom phospholipase A2 (bvPLA2)
Received: 13 Jul 2019;
Accepted: 07 Oct 2019.
Copyright: © 2019 Ham, Han, Lee, Kim, Yun, Kim and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Jin Tae Hong, Chungbuk National University, Cheongju, 361-763, North Chungcheong, South Korea, firstname.lastname@example.org