Echinacea-Induced Macrophage Activation

Abstract

Public interest in Echinacea is growing rapidly. Unfortunately, there is little scientific evidence to support claims of efficacy of this widely used botanical, and little information about potential mechanism of action. This study examines the ability of Echinacea to upregulate macrophage function and begins to elucidate the mechanism of Echinacea-induced macrophage activation. Murine peritoneal macrophages were cultured with E. purpurea extracts enriched for plant polysaccharide (EP). ELISA was used to measure cytokine production. MAPKs were blocked using specific inhibitors, and Western blotting used to identify phosphorylated proteins involved in signal transduction. To examine in vivo efficacy, EP was administered orally and Listeria monocytogenes given i.v. Mice were sacrificed three days post-infection to determine bacterial load in the spleen. We demonstrate that an endotoxin-free EP extract activates the innate immune response, stimulating production of IL-6, TNF, IL-12, and NO from macrophages in vitro. Along with evidence of enhanced macrophage function, we found that oral EP reduces bacterial burden during infection by Listeria monocytogenes, demonstrating its efficacy in vivo. EP initiates a signaling cascade within macrophages through both TLR4-dependent and -independent mechanisms, involving ERK, p38 and JNK, and ultimately the activation of NF-kappaB.

Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells

“…Adding specific p38 MAPK inhibitors reversed the harmful effects induced by khat, suggesting that p38 MAPK is a key player in the khat-induced altered phenotype of cells. Other plant extracts such as Sauchinone (Huang et al, 2009), and Antrodia camphorate (Jeong et al, 2009) up-regulate p38 expression in human cells and Echinacea (Sullivan et al, 2008) and areca beetle nut extracts (Hung et al, 2007) activate PBMC by initiating signalling cascades within cells involving phosphorylation of p38 MAPK. Interestingly, khat also increased the expression of the transcription factor HIF-1␣ in PBMC.…”

In Vivo Efficacy of Drugs against <i>Toxoplasma gondii</i> Combined with Immunomodulators

“…In vivo and in vitro studies have shown that E. purpurea activates the natural immune response by stimulating interleukin (IL)-6, IL-12, and nitric oxide (NO), and tumor necrosis factor (TNF) in the macrophages; it also demonstrates immunomodulatory effects by increasing macrophagemediated phagocytosis (12)(13)(14)(15).…”

“…Thymopoietin affects many components of the immune system, and its therapeutically important actions probably target the stimulation of phagocytosis and regulartory T cells to restore homeostasis in a perturbed immune system. Levamisole has also been used to treat a variety of dermatological conditions, including skin infections (12)(13)(14)(15)(16).…”

Activation of J774.1 murine macrophages by lactate dehydrogenase

“…An aqueous extract from Phyllanthus niruri enhanced phagocytosis, the lysosomal enzyme activity, and TNF-a release by bone marrow-derived macrophages (Nworu et al 2010). It was also reported that an endotoxin-free Echinacea extract stimulated production of IL-6, TNF-a, IL-12, and nitric oxide by toll-like receptor (TLR) 4-dependent and TLR4-independent mechanisms in murine peritoneal macrophages (Sullivan et al 2008). These reports concluded that these plant extracts that activate macrophages may enhance both the humoral and cellular immune responses to promote the host defense.…”