title: Evaluation of sage phenolics for their antileishmanial activity and modulatory effects on interleukin-6, interferon and tumour necrosis factor-alpha-release in RAW 264.7 cells.
abstract: A series of sage phenolics was tested for activity against a panel of Leishmania parasites and for immunomodulatory effects on macrophage functions including release of tumour necrosis factor (TNF), interleukin-6 (IL-6), and interferon (IFN)-like activities. For this, functional bioassays were employed including an in vitro model for leishmaniasis in which macrophage-like RAW 264.7 cells were infected with Leishmania parasites, an extracellular Leishmania growth-inhibition assay, a fibroblast-lysis assay for TNF-activity, a cell proliferation assay using IL-6 sensitive murine B9 hybridoma cells, and a virus protection assay for IFN-like activity. Whereas none of the test samples exhibited marked activities against extracellular Leishmania promastigotes (IC50 > 700 to > 2800 nM; > 500 microg/ml), caffeic acid, salvianolic acids K and L as well as the methyl ester of salvianolic acid I showed pronounced antileishmanial activities against intracellular amastigote stages within RAW cells (IC50 3-23 nM vs. 10-11 nM for the reference Pentostam). Noteworthy, the phenolic samples showed no cytotoxicity against the host cells (IC50 > 600 to > 2200 nM; > 400 microg/ml). Tested sage phenolics activated Leishmania-infected RAW 264.7 for release of TNF ranging 22-117 U/ml and IL-6 ranging 3-42 U/ml. In contrast, their TNF- or IL-6-inducing potential in experiments with non-infected host cells was negligible. Furthermore, caffeic acid and salvianolic acid K induced a modest release of IFN-like activity (5-9 and 2-4 U/ml, respectively) as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on L929 cells. The results support the emerging picture that plant polyphenols may be credited for the profound health-beneficial properties of various herbal medicines and agricultural products.
authors.affiliation: Institut für Pharmazie, Pharmazeutische Biologie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, D-14195 Berlin, Germany.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Radtke
authors.forename: Lai Yeap
authors.initials: LY
authors.lastname: Foo
authors.forename: Yinrong
authors.initials: Y
authors.lastname: Lu
authors.forename: Albrecht F
authors.initials: AF
authors.lastname: Kiderlen
authors.forename: Herbert
authors.initials: H
authors.lastname: Kolodziej
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015850:Interleukin-6 / Q000378:metabolism*; D007891:Leishmania / Q000187:drug effects*; D008264:Macrophages; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008517:Phytotherapy; D027543:Salvia officinalis / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000981:Antiprotozoal Agents; D002109:Caffeic Acids; D015850:Interleukin-6; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; C040048:caffeic acid