Echinacea, Hypericum and Prunella have been found to have appreciable anti-inflammatory activity. Thisactivity may result from 1) an inhibition of inflammatory factors and/or, 2) an enhancement of anti-inflammatory cytokines. The health benefits of Echinacea, Hypericum, and Prunella extracts may directlyresult from a reduction in inflammation and an associated reduction in symptoms, and these potentialbenefits may extend to diseases with an inflammatory component. This Project will focus on understandingthe balance between the anti- and pro-inflammatory activities of these supplements, both in cell and animalmodels, and on probing their mechanisms of action in cell systems. The overarching hypothesis underinvestigation is that the anti-inflammatory activity of fractions prepared from Echinacea, Prunella, orHypericum is due to interacting constituents that shift the complex balance of immune-modulators toward ananti-inflammatory profile by modulating key signal transduction pathways and subsequent gene expression.
Three Specific Aims are proposed: 1) Assessing the effects of Echinacea, Prunella, and Hypericumperforatum accessions, fractions and compounds on pro-inflammatory / anti-inflammatory cytokine andchemokine balance, in cultured cell populations with and without immune stimulation (primary lymphocytesand monocyte/macrophages, and the following cell lines: the RAW264.7 macrophage cell line, the A549human bronchial epithelial cell line, and the MODE-K murine colonic epithelial cell line). 2) Assessing therole of Echinacea, Hypericum and Prunella in minimizing immunopathology and inflammation in establishedanimal models of respiratory viral infection that result in acute pulmonary inflammation (influenza) andinflammatory disease (dextran sulfate sodium [DSS]-induced colitis model of inflammatory bowel disease).3) Evaluating the effects of fractions and constituents of Echinacea and H. perforatum accessions on cellularsignaling pathways that regulate in the severity of inflammation. We will initially use microarraysto identifythe key interacting pathways that are altered by constituents and fractions of Echinacea and Hypericum (Aim3.a). We will then use western blots, phosphorylation analysis, immune complex kinase assays, and gel shifttechnologies to further delineate the underlying mechanisms that regulate the activation of the key pathways(Aim 3.b). The proposed studies will further our understanding of Echinacea, Hypericum and Prunellaconstituents that contribute to the anti-inflammatory activity of these genera and determine if these genera,may be of value in treating inflammatory processes in the lung and colon. Furthermore, the proposedstudies will assess the cellular mechanisms underlying these benefits, focusing on signaling pathways thathave been shown to be central in regulating pro- and anti-inflammatory processes.
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