Inhibitory Effects of Coptis japonica Alkaloids on the LPS-Induced Activation of BV2 Microglial Cells

Abstract

-Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

Kaempferol and Kaempferol Rhamnosides with Depigmenting and Anti-Inflammatory Properties

“…Next, we evaluated the anti-inflammatory activity by measuring both the inhibition of the nitric oxide (NO) production [ 11 ] and the suppression of the NF-κB-mediated luciferase assays [ 12 ]. We estimated the inhibitory activity of kaempferol and its rhamnosides relative to NO production, induced by LPS in RAW264.7 cells, and the NF-κB-mediated luciferase activity relative to a non-specific phosphodiesterase inhibitor such as pentoxifylline and BAY11-7082, an IκBα kinase inhibitor, as positive controls.…”

Anti-inflammatory activity of ethanol extract derived from Phaseolus angularis beans

“…Although we did not test whether these compounds directly acted as anti-inflammatory agents, proanthocyanidins or polyphenols, such as vitexin, appear to be important components based on previous reports (Ho et al, 2007;Jeon et al, 2009). In mice, vitexin-containing extracts showed strong antiinflammatory activity in croton oil ear tests (Picerno et al, 2006).…”

Regulatory Effect of Cinnamaldehyde on Monocyte/Macrophage-Mediated Inflammatory Responses

“…The cells were used for experiments 48 h after transfection. Luciferase assays were performed using the Luciferase Assay System (Promega) [ 22 ].…”