Neferine, is a major alkaloid present in the green embryos of Nelumbo nucifera Gaertn with anti-arrhythmia, anti-hypertensive and vaso-relaxant properties , and is also aNF-κB inhibitor.
The nuclear factor kappaB (NF-kappaB) is a ubiquitously expressed transcription factor playing vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation[2]. Neferine, is a major alkaloid present in the green embryos of Nelumbo nucifera Gaertn with anti-arrhythmia, anti-hypertensive and vaso-relaxant properties, and is also a NF-κB inhibitor. Neferine could inhibit LPS-ATP-induced oxidative stress and the activation of NLRP3 inflammasome signaling, and increased the endothelial cell viability and SOD production. siRNA which mediated the knockdown of NLRP3 promoted the neferine-induced inhibition effects of cell pyroptosis. Furthermore, these neferine-induced effects were reversed by the over-expression of NLRP3[3]. Neferine was distributed rapidly into different organ systems, with the highest concentrations found in the liver. In animal (rat) studies, neferine is known to be predominantly metabolized in the liver and undergoes initial bioconversion by CYP2D6 into liensinine, isoliensinine, dimethylliensinine, and dimethyl-isoliensinine[4]. The human lung adenocarcinoma A549 cells upon treatment with neferine induced cell cycle arrest in G1 phase and further induced apoptosis in a dose dependent manner along with events such as over production of reactive oxygen species, lipid peroxidation, depletion of the mitochondrial membrane potential, loss of cellular pool of anti-oxidants, MAPKs activation, DNA fragmentation and intracellular calcium accumulation[5]. Hep3B cells treated with neferine undergo cell cycle arrest, ER stress and apoptosis through activation of Bid, Bim, Puma, Bak,Bax, caspase-3, -6, -7, -8 and PARP. The upregulated proteins due to neferine include calcinexin,calpain-2, Bip, PDI and caspase-12. Formation of autophagosomes along with reduced migration ability in the Hep3B cells is also observed due to neferine treatment[6].
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