Bee venom phospholipase A2 ameliorates amyloidogenesis and neuroinflammation through inhibition of signal transducer and activator of transcription-3 pathway in Tg2576 mice

Background:Neuroinflammation and accumulation ofβ-amyloid(Aβ)play a significant role in the onset and progression of Alzheimer’s disease(AD).Our previous study demonstrated that signal transducer and activator of transcription-3(STAT3)plays a major role in neuroinflammation and amyloidogenesis.Methods:In the present study,we investigated the inhibitory effect of bee venom phospholipase A2(bvPLA2)on memory deficiency in Tg2576 mice,which demonstrate genetic characteristics of AD and the mechanism of its action at the cellular and animal level.For in vivo study,we examined the effect of bvPLA2 on improving memory by conducting several behavioral tests with the administration of bvPLA2(1 mg/kg)to Tg2576 mice.For in vitro study,we examined the effect of bvPLA2 on amyloidogenesis and neuroinflammation by treating bvPLA2 on LPSactivated BV2 cells.Results:We found that bvPLA2 alleviated memory impairment in Tg2576 mice,as demonstrated in the behavioral tests assessing memory.In the bvPLA2-treated group,Aβ,amyloid precursor protein(APP),and β-secretase 1(BACE1)levels and β-secretase activity were significantly decreased.Expression of pro-inflammatory cytokines and inflammation-related proteins decreased in the brain of bvPLA2-treated group,whereas anti-inflammatory cytokines increased.In addition,bvPLA2 reduced STAT3 phosphorylation in the brains of the bvPLA2-treated group.At the cellular level,bvPLA2 inhibits production of nitric oxide,pro-inflammatory cytokines,and inflammation-related proteins including p-STAT3.Additionally,bvPLA2 inhibits the production of Aβin cultured BV-2 cells.Results from the docking experiment,pull-down assay,and the luciferase assay show that bvPLA2 directly binds STAT3 and,thus,regulates gene expression levels.Moreover,when the STAT3 inhibitor and bvPLA2 were administered together,the anti-amyloidogenic and anti-inflammatory effects were further enhanced than when they were administered alone.Conclusion:These results suggest that bvPLA2 could restore memory by inhibiting the accumulation of Aβ and inflammatory responses via blockage of STAT3 activity.

Effects of aqueous extract from red Liriope platyphylla on phthalic-anhydride-induced atopic dermatitis in Interleukin-4/Luciferase/Consensus non-coding sequence-1 transgenic mice evaluated in terms of luciferase signal and general phenotype biomarkers

OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phthalic anhydride(PA) treated Interleukin-4(IL-4)/Luc/Consensus non-coding sequence-1(CNS-1) transgenic(Tg) mice following treatment with aqueous extract of RLP(AEt RLP) for4 weeks.METHODS: Alterations in AD phenotypes were measured in IL-4/Luc/CNS-1 Tg mice following treatment with AEt RLP using inflammation parameter analysis, bioluminescence imaging analysis, histological analysis, reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and Western blot analysis.RESULTS: RLP contained high concentrations of total phenolic compounds, total flavonoid compounds and 5-HNE related to AD therapy. The Luc signal was only detected in the abdominal region and the submandibular lymph node(SL), mesenteric lymph node(ML), thymus and pancreas of the PA treated group. This signal was significantly decreased by 28%-73% throughout the body and in the four organs in PA + AEt RLP treated group. Furthermore, the lymph node weight, immunoglobulin E concentration and dermal thickness were decreased by 37%-67% in the PA + AEt RLP treated group.CONCLUSION: Our findings suggest that the therapeutic effect of AEt RLP on PA induced AD could be successfully quantified by comparison of Luc signals and AD phenotype markers in IL-4/Luc/CNS-1Tg mice, and that the Luc signal was as sensitive as the general AD phenotypes, enabling detection of effects without euthanasia.