Piperine modulates NLRP3 / TLR4 / NF-κB signalling processes of angiogenesis and neurogenesis in rats following ischemic stroke

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Abstract

Early studies have shown neurotrophic and neuroprotective functions and have grown considerably in the treatment of brain aging-related disorders correlated with age, but their fundamental role against ischaemic stroke remains unclear in MCAO (middle cerebral artery occlusion) induced rats. In this research, we evaluated the influence of piperine on angiogenesis and neurogenesis in ischemic rats and subsequently identified the fundamental mechanism of NF-κB /NLRP3/ TLR4 signaling pathways. In rats, MCAO was conducted to cause ischemic stroke and 2,3,5-Triphenyltetrazolium chloride staining (TTC) staining was utilized to assess if the MCAO procedure was effectively developed. The assessment of neurological disorder was carried out. Immunofluorescence staining was studied to evaluate the influence of neurogenesis and angiogenesis after oral dosing (5 or 10 mg/kg) of piperine in MCAO triggered rats. Besides, by western blotting analysis, the proteins (Caspase-1, IL-1β, NLRP3, TLR4, NF-κB p65) active in the signaling cascade TLR4/NF-2B/NLRP3 were identified. The number of neurons in the infant and brain microvessel density (MVD) following ischemic stroke was greatly improved during the treatment with piperine. Treatment of piperine significantly suppressed Caspase-1, IL-1β, NLRP3, TLR4, NF-κB p65 proteins implicated in the signaling process of NF-kB /NLRP3/ TLR4. Piperine improves neurogenesis and angiogenesis by modulation of the inflammatory signaling cascade of NF-kB /NLRP3/ TLR4 after ischemic stroke in rats. Therefore, piperine could be a successful drug for the inhibition of ischemic stroke.

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Yang, J., Sheng, Y., Lu, Y., & Zhao, Y. (2021). Piperine modulates NLRP3 / TLR4 / NF-κB signalling processes of angiogenesis and neurogenesis in rats following ischemic stroke. Acta Poloniae Pharmaceutica - Drug Research, 78(2), 253–261. https://doi.org/10.32383/APPDR/135847

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