Inhibitory Effect of Piperlonguminine/Dihydropiperlonguminine on the Production of Amyloid β and APP in SK-N-SH Cells

Qi, Hong-Shun; Pei, Lei; Gao, Shaopeng; Diao, Zengyan; Yang, Lingling; Xu, Jiacheng; Qu, Xun; Han, Eunyoung

doi:10.4077/cjp.2009.amh062

Cited by 13 publications

(4 citation statements)

References 26 publications

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“…1A), a pyridone alkaloid found in the fruit of the long pepper, Piper longum Linn [3]. PL has recently been demonstrated to have beneficial effects on a plethora of pathophysiologic pathways involved in the natural history of major human diseases; e.g., oxidative stress [4], inflammation [5], hemostasis [6], hyperlipidemia [7], dementia [8] and pain [9]. Furthermore, PL inhibits infectious pathogens (e.g., amoebae [10], schistosoma [11], fungi [12]) or their insect vectors (e.g., mosquitoes at larval [13] or adult [14] stages of development); protects tissues, such as liver, from damage induced by toxic chemicals [15] or ionizing radiation [16]; and, of importance for cancer research, hampers the growth and dissemination of neoplastic cells in vitro [17] and in vivo [18].…”

Section: Introductionmentioning

confidence: 99%

Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro

et al. 2013

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Piperlongumine (PL), a pepper plant alkaloid from Piper longum, kills solid tumor cells in a highly selective, potent fashion. To evaluate whether PL may have similar effects on malignant blood cells, we determined the efficacy with which PL inhibits the B-lymphocyte derived neoplasm, Burkitt lymphoma (BL). Low micromolar concentrations of PL (IC50 = 2.8 × 8.5 μM) curbed growth and survival of two EBV+ BL cell lines (Daudi, Raji) and two EBV− BL cell lines (Ramos, DG-75), but left normal peripheral blood B-lymphocytes unharmed. PL-dependent cytotoxicity was effected in part by reduced NF-κB and MYC activity, with the former being caused by inhibition of IκBα degradation, nuclear translocation of p65, and binding of NF-κB dimers to cognate DNA sequences in gene promoters. In 4 of 4 BL cell lines, the NF-κB/MYC-regulated cellular target genes, E2F1 and MYB, were down regulated, while the stress sensor gene, GADD45B, was up regulated. The EBV-encoded oncogene, LMP-1, was suppressed in Daudi and Raji cells. Considering that NF-κB, MYC and LMP-1 play a crucial role in the biology of many blood cancers including BL, our results provide a strong preclinical rationale for considering PL in new intervention approaches for patients with hematologic malignancies.

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Section: Introductionmentioning

confidence: 99%

Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro

et al. 2013

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“…We have also previously showed that piperlonguminine/ dihydropiperlonguminine components isolated from Futokadsura stem inhibits the expression of APP and Aβ in SK-N-SH cells (19,29). Do the APP and Aβ inhibition effects of the components occur in vivo?…”

Section: Discussionmentioning

confidence: 88%

Neuroprotective Effects of an Aqueous Extract of Futokadsura Stem in an Aβ-Induced Alzheimer's Disease-Like Rat Model

Xia

Xiang

et al. 2015

Chin. J. Physiol.

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Futokadsura stem has been traditionally used to dispel wind-damp obstruction syndrome manifested as painful and stiff joints, tendon and muscle spasms, lower back pain, painful knees and pain from external injury. An aqueous extract of Futokadsura stem has previously been found to have neuro-protective effects in vitro. In this study, we aimed to investigate if the Futokadsura stem extract could protect the neuron in the brain of an Aβ-induced Alzheimer's Disease (AD)-like rat model by improving the learning and memory ability of the rats. Learning and memory ability of the rats were measured by the Morris water maze test. Neuronal morphology in the hippocampus was examined by HE staining. Expression levels of Aβ, TNF-α, IL-6 and synaptophysin (SYP) were measured by immunofluorescence. Nitric oxide (NO) and nitric oxide synthase (NOS) levels were measured by NO and NOS detecting kit. We found that aqueous extract of Futokadsura stem alleviated Aβ(25-35)-induced impairment of spatial learning and memory in the AD rats. Furthermore, the extract protected the neurons by decreasing the expression of Aβ, TNF-α and IL-6 and the content of NO and NOS in the brain, and increasing the expression of SYP in the hippocampus. Our data indicated that aqueous extract of Futokadsura stem improved the learning and memory ability of AD rats. The neuro-protective effect was accomplished probably by depressing inflammation and oxidative stress in the brain.

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“…Inhibitory effects of PL on NF-κB activity have been reported in atherosclerotic plaque formation and in the prevention of Burkitt lymphoma and prostate cancer cell growth (Son et al 2012 ; Han et al 2013 ; Ginzburg et al 2014 ). Qi et al ( 2009 ) reported that PL had an inhibitory effect on the production of Aβ and APP in SK–N–SH cells. Taken together, our results indicate that PL administration prevented LPS-induced memory impairment by blocking NF-κB and consequently inhibiting amyloidogenesis.…”

Section: Discussionmentioning

confidence: 99%

Piperlongumine Improves Lipopolysaccharide-Induced Amyloidogenesis by Suppressing NF-KappaB Pathway

Lee

Ham

et al. 2018

Neuromol Med

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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-κB). Piperlongumine (PL) is an alkaloid amide found naturally in long pepper (Piper longum) isolates; it was reported to have inhibitory effects on NF-κB activity. We therefore investigated whether PL exhibits anti-inflammatory and anti-amyloidogenic effects by inhibiting NF-κB. 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 µg/mL) or PL (0.5 or 1.0 or 2.5 µM). Results from our behavioral tests showed that PL inhibited LPS-induced memory. PL also prevented LPS-induced beta-amyloid (Aβ) accumulation and inhibited the activities of β- and γ-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-κB 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-κB signaling; PL therefore demonstrates potential for the treatment of Alzheimer’s disease.

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Inhibitory Effect of Piperlonguminine/Dihydropiperlonguminine on the Production of Amyloid β and APP in SK-N-SH Cells

Cited by 13 publications

References 26 publications

Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro

Piperlongumine inhibits proliferation and survival of Burkitt lymphoma in vitro

Neuroprotective Effects of an Aqueous Extract of Futokadsura Stem in an Aβ-Induced Alzheimer's Disease-Like Rat Model

Piperlongumine Improves Lipopolysaccharide-Induced Amyloidogenesis by Suppressing NF-KappaB Pathway

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