title: Biological activities of xanthatin from Xanthium strumarium leaves.
abstract: The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis.
authors.affiliation: Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany.
authors.forename: Endalkachew
authors.initials: E
authors.lastname: Nibret
authors.forename: Mahamoud
authors.initials: M
authors.lastname: Youns
authors.forename: R Luise
authors.initials: RL
authors.lastname: Krauth-Siegel
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D031210:Xanthium / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D005663:Furans; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D014344:Trypanocidal Agents; C022186:xanthatin; D001094:Arachidonate 5-Lipoxygenase; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D015232:Dinoprostone