Impact of novel N-aryl substituted piperamide on NF-kappa B translocation as a potent anti-neuroinflammatory agent

Shahbazi, Sajad; Zakerali, Tara; Frycz, Bartosz Adam; Kaur, Jagdeep

doi:10.1016/j.biopha.2020.110199

Cited by 12 publications

(5 citation statements)

References 12 publications

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Section: Discussionmentioning

confidence: 99%

“…LPS activate NLRP3 in BV2 cells by translocating NF‐κB p65 from the cytoplasm to the nucleus 49 . There, it regulates the expression of several inflammatory mediators, which cause neuronal receptors to activate protein kinases, trigger inflammation, and accelerate neurodegeneration 50 …”

Section: Discussionmentioning

confidence: 99%

“…49 There, it regulates the expression of several inflammatory mediators, which cause neuronal receptors to activate protein kinases, trigger inflammation, and accelerate neurodegeneration. 50 We explored the mechanism underlying the antineuroinflammatory and anti-oxidative effects of hUC-MSC exosomes. Increased ROS generation activated the microglia, whereas reduced mitochondrial ROS accumulation alleviated the NLRP3 inflammasome activation.…”

Section: Con Clus Ionmentioning

confidence: 99%

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Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway

Che,

Wang,

Dong

et al. 2023

CNS Neurosci Ther

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AimsWe investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation.MethodsExosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H2O2 was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting.ResultsTreatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H2O2‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes.ConclusionhUC‐MSC‐derived exosomes ameliorated LPS/H2O2‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Con Clus Ionmentioning

confidence: 99%

See 1 more Smart Citation

Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway

Che,

Wang,

Dong

et al. 2023

CNS Neurosci Ther

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“…Piperine, a crystalline alkaloid extracted from pepper, has several properties such as anticarcinogenic, stimulatory, anti-inflammatory and antiulcer activities (59). Furthermore, piperine derivatives, such as (2E,4E)-5-(benzo[d] [1,3]dioxo l-5-yl)-N- [4-(hydroxymethyl) phenyl] penta-2,4-dienamide (D4) have demonstrated anti-neuroinflammatory effects (60) by inhibiting the translocation of NF-κB and suppressing the expression of iNOS and the secretion of NO, TNF-α, and IL-1β in LPS-induced human microglia clone 3. In addition, an in silico study showed excellent d4 bioavailability after oral administration (61).…”

Section: Nf-κb (Nuclear Factor-kappa-b)mentioning

confidence: 99%

Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review)

Zheng,

Zhang,

Zhang

et al. 2023

Int J Mol Med

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The intricate nature of Alzheimer's disease (AD) pathogenesis poses a persistent obstacle to drug development. In recent times, neuroinflammation has emerged as a crucial pathogenic mechanism of AD, and the targeting of inflammation has become a viable approach for the prevention and management of AD. The present study conducted a comprehensive review of the literature between October 2012 and October 2022, identifying a total of 96 references, encompassing 91 distinct pharmaceuticals that have been investigated for their potential impact on AD by inhibiting neuroinflammation. Research has shown that pharmaceuticals have the potential to ameliorate AD by reducing neuroinflammation mainly through regulating inflammatory signaling pathways such as NF-κB, MAPK, NLRP3, PPARs, STAT3, CREB, PI3K/Akt, Nrf2 and their respective signaling pathways. Among them, tanshinone IIA has been extensively studied for its anti-inflammatory effects, which have shown significant pharmacological properties and can be applied clinically. Thus, it may hold promise as an effective drug for the treatment of AD. The present review elucidated the inflammatory signaling pathways of pharmaceuticals that have been investigated for their therapeutic efficacy in AD and elucidates their underlying mechanisms. This underscores the auspicious potential of pharmaceuticals in ameliorating AD by impeding neuroinflammation.

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“…Other compounds such as curcumin have also been found to modulate lipid peroxidation, HO-1 levels, suppression of malondialdehyde (MDA) levels, increasing glutathione and CAT and Nrf2 activities to produce neuroprotective or anti-ageing effects in different models of NDDs [ 262 ], capsaicin decreased brain MDA whereas increased GSH and paraoxonase-1 activity in pentylene-tetrazole-induced Seizures [ 263 ], piperamide was found to inhibit NF-κB translocation [ 264 ] and activated the Nrf2/HO-1 pathway to induce anti-inflammation in different neuroinflammatory disease models [ 265 ]…”

Section: Phytoconstituents’ Other Modes Of Action In Nddsmentioning

confidence: 99%

Role of Phytoconstituents as PPAR Agonists: Implications for Neurodegenerative Disorders

2021

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Peroxisome proliferator-activated receptors (PPAR-γ, PPAR-α, and PPAR-β/δ) are ligand-dependent nuclear receptors that play a critical role in the regulation of hundreds of genes through their activation. Their expression and targeted activation play an important role in the treatment of a variety of diseases, including neurodegenerative, cardiovascular, diabetes, and cancer. In recent years, several reviews have been published describing the therapeutic potential of PPAR agonists (natural or synthetic) in the disorders listed above; however, no comprehensive report defining the role of naturally derived phytoconstituents as PPAR agonists targeting neurodegenerative diseases has been published. This review will focus on the role of phytoconstituents as PPAR agonists and the relevant preclinical studies and mechanistic insights into their neuroprotective effects. Exemplary research includes flavonoids, fatty acids, cannabinoids, curcumin, genistein, capsaicin, and piperine, all of which have been shown to be PPAR agonists either directly or indirectly. Additionally, a few studies have demonstrated the use of clinical samples in in vitro investigations. The role of the fruit fly Drosophila melanogaster as a potential model for studying neurodegenerative diseases has also been highlighted.

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Impact of novel N-aryl substituted piperamide on NF-kappa B translocation as a potent anti-neuroinflammatory agent

Cited by 12 publications

References 12 publications

Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway

Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway

Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review)

Role of Phytoconstituents as PPAR Agonists: Implications for Neurodegenerative Disorders

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