phorbol and Inflammation

Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses - namely diarrhoea, inflammation, liver disorders, snake bite and fever - are linked - at least in part - to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50 is approximately equal to 10 μg/mL), COX-1(IC50 is approximately equal to 50 μg/mL), and 12-LOX (IC50 is approximately equal to 170 μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2 is not probable, but the extract induced the synthesis of the anti-inflammatory eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided fractionation of the crude extract led to the isolation of ziniolide, a known 12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the n-hexane extract (IC50=69 μM). Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NFκB activation, a key regulator of the arachidonic pathway.

Topics: Anti-Inflammatory Agents; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; HeLa Cells; Humans; Hydroxyeicosatetraenoic Acids; Inflammation; Inhibitory Concentration 50; Lipoxygenase Inhibitors; Lipoxygenases; NF-kappa B; Phorbols; Phytotherapy; Plant Extracts; Plant Roots; Sesquiterpenes, Guaiane; Xanthium