Identification and pharmacological characterization of the anti-inflammatory principal of the leaves of dwarf elder (Sambucus ebulus L.).
OBJECTIVE
The performed investigations aimed on the identification of the anti-inflammatory principal of extracts of leaves of Sambucus ebulus L. (dwarf elder) in order to rationalize the traditional use of this plant for the treatment of chronically inflammatory diseases.


METHODS
Dwarf elder leaf extract was subjected to activity guided fractionation using inhibition of TNFα induced expression of vascular cell adhesion molecule 1 (VCAM-1) on the surface of human umbilical vein endothelial cells (HUVECs) as monitoring tool (positive control: parthenolide 10μM, VCAM-1 expression (% of control): 5.35±0.38%).


RESULTS
Bio-guided isolation resulted in identification of ursolic acid as anti-inflammatory principal. Besides its inhibitory effects against TNFα induced expression of VCAM-1 (IC(50) 6.25 μM), ursolic acid inhibits also TNFα induced expression of ICAM-1 (IC(50) value between 3.13 and 6.25 μM) (positive control: parthenolide 10 μM, ICAM-1 expression (% of control): 38.89±16.6%). Toxic effects of ursolic acid on HUVECs can be drastically reduced using an enriched extract instead of the pure compound.


CONCLUSIONS
Our findings suggest an additional mechanism of the anti-inflammatory activity of ursolic acid by demonstrating its ability to inhibit TNFα-stimulated expression of VCAM-1 and ICAM-1 and support the traditional use of extracts and preparations of Sambucus ebulus L., rich in ursolic acid, for the treatment of chronically inflammatory processes.
Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Josef-Moeller-Haus, Innrain 52c, A-6020 Innsbruck, Austria. Stefan.Schwaiger@uibk.ac.at
Stefan
S
Schwaiger
Iris
I
Zeller
Petra
P
Pölzelbauer
Sandra
S
Frotschnig
Günther
G
Laufer
Barbara
B
Messner
Valerio
V
Pieri
Hermann
H
Stuppner
David
D
Bernhard
D000893:Anti-Inflammatory Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D020834:Ethnopharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D027923:Sambucus / Q000737:chemistry; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000097245:Ursolic Acid
D000893:Anti-Inflammatory Agents; D018799:Intercellular Adhesion Molecule-1; D010936:Plant Extracts; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000097245:Ursolic Acid