Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells

Abstract

Inflammation is important and has been found to be an underlying cause in many acute and chronic human diseases. Nuciferine, a natural alkaloid containing an aromatic ring, is found in the nelumbo nucifera leaves. It has been shown to have potential anti-inflammatory activities, but the molecular mechanism has remained unclear. In this study, we found that nuciferine (10 μM) significantly inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokine IL-6 and TNF-α production in RAW 264.7 cells. In addition, the luciferase reporter assay results of different subtypes of the peroxisome proliferator-activated receptor (PPAR) showed that nuciferine dose-dependently activated all the PPAR activities. Specific inhibitors of PPARα and PPARγ significantly abolished the production of inflammatory cytokines as well as IκBα degradation. However, PPARδ inhibitor did not show this effect. Our results suggested a potential molecular mechanism of the anti-inflammatory effects of nuciferine in LPS-induced inflammation, at least in part, by activating PPARα and PPARγ in RAW 264.7 cells.

The Effect of Sacred Lotus (Nelumbo nucifera) and Its Mixtures on Phenolic Profiles, Antioxidant Activities, and Inhibitions of the Key Enzymes Relevant to Alzheimer’s Disease

“…All sacred lotus parts contain high bioactive compounds, and have been used for pharmacological purposes such as anti-oxidative, astringent, emollient, diuretic [ 6 ], anti-diabetic [ 8 ], anti-hyperlipidemic [ 9 ], anti-aging [ 6 , 10 ], anti-ischaemia [ 11 ], anti-viral [ 12 ], anti-inflammatory [ 13 , 14 ], anti-allergic [ 15 ], anti-cancer [ 16 ], and hepatoprotective effects [ 17 ]. Interestingly, sacred lotus extracts were also previously reported to affect neurodegenerative disorders, especially Alzheimer’s disease (AD) [ 18 , 19 , 20 ].…”

Comparison of PPAR Ligands as Modulators of Resolution of Inflammation, via Their Influence on Cytokines and Oxylipins Release in Astrocytes

“…Firstly, the effects of the so-called PPAR antagonists themselves. Indeed, in relation to the cells of macrophage origin (RAW 264.7), all three PPAR subtype antagonists (GW5417; GSK0660; GW9662) increased TNFα synthesis by 12 h in the LPS-stimulated cells [ 67 ]. We identified that GSK0660 and GW9662 inhibited TNFα synthesis by 6 h on LPS-stimulated astrocytes.…”

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

“…Many powerful chemotherapy drugs such as doxorubicin, teniposide, and etoposide are topoisomerase II inhibitors [205]. However, serious side effects could result from using these drugs due to the lack of selectivity as well as the risk of drug resistance due to the enzymes' gene mutation or dysregulation of their expression in tumor cells [194,[207][208][209]. Thus, looking for new phytochemicals that targeting topoisomerases enzyme is a promising branch in chemotherapy development.…”

“…On the other hand, resveratrol repressed the hypoxia-induced resistance to doxorubicin in MCF-7 cells via downregulation of HIF-1α protein expression [208]. Nuciferine is an aromatic alkaloid extracted from lotus leaves that exhibited anti-inflammatory, antioxidant, and anticancer properties [209,233,234]. Recently, nuciferine has been applied in drug-resistant tumor cells, and it was able to regulate MDR proteins as well as reduce the activation of Nrf2 and HIF-1α [235].…”