Journal
NEUROMOLECULAR MEDICINE
Volume 20, Issue 3, Pages 312-327Publisher
HUMANA PRESS INC
DOI: 10.1007/s12017-018-8495-9
Keywords
Alzheimer's disease; Piperlongumine; Beta-amyloid; Nuclear factor kappaB; Amyloidogenesis; Neuroinflammation
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Funding
- NRF - Korea government (MSIP) [2017R1A5A2015541]
- NRF - Korea government (MEST) [2015R1A6A1A0420885]
- Marine Biotechnology Program - MOF, Korea [20150184]
- National Research Foundation of Korea [2017R1A5A2015541] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Amyloidogenesis is known to cause Alzheimer's disease. Our previous studies have found that lipopolysaccharide (LPS) causes neuroinflammation and amyloidogenesis through activation of nuclear factor kappaB (NF-kappa B). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF-kappa B activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-kappa B. A murine model of LPS-induced memory impairment was made via the intraperitoneal (i.p.) injection of LPS (0.25 mg/kg/day, i.p.). We then injected PL (1.5 or 3.0 mg/kg/day, i.p.) for 7 days in three groups of mice to observe effects on memory. We also conducted an in vitro study with astrocytes and microglial BV-2 cells, which were treated with LPS (1 A mu g/mL) or PL (0.5 or 1.0 or 2.5 A mu M). Results from our behavioral tests showed that PL inhibited LPS-induced memory. PL also prevented LPS-induced beta-amyloid (A beta) accumulation and inhibited the activities of beta- and gamma-secretases. The expression of inflammatory proteins also was decreased in PL-treated mice, cultured BV-2, and primary astrocyte cells. These effects were associated with the inhibition of NF-kappa B activity. A docking model analysis and pull-down assay showed that PL binds to p50. Taken together, our findings suggest that PL diminishes LPS-induced amyloidogenesis and neuroinflammation by inhibiting NF-kappa B signaling; PL therefore demonstrates potential for the treatment of Alzheimer's disease.
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