Radtke OA, Foo LY, Lu Y, Kiderlen AF, Kolodziej H (2003): 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
Z. Naturforsch. 58c: 395-400.

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 µg/ ml), caffeic acid, salvianolic acid K and the methyl ester of salvianolic acid I showed pronounced antileishmanial activities against intracellular amastigote stages within RAW 264.7 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 µg/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 respective 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.