In vitro activity: Evodiamine (Isoevodiamine), an alkaloid extract from Evodiae Fructus exhibits antitumor activities against the human tumor cells. Evodiamine induces the substantial amount of apoptosis both in Bcl-2- and Akt-overexpressing U937 cells but not in human peripheral blood mononuclear cells via caspase-independent apoptotic pathways. Evodiamine Evodiamine also inhibits tumor necrosis factor (TNF)-induced NF-kappaB and Akt activation but it has no effect on JNK or p38 MAPK activation. In addition, Evodiamine is an human topoisomerase I inhibitor.

Kinase Assay: Evodiamine is a quinozole alkaloid isolated from Evodia rutaecarpa, described as an agonist of the VR1 (vanilloid receptor subtype 1, TRPV1) with affinity (Ki = 5.95 microM) comparable to that of the prototypical VR1 chemical activator Capsaicin (sc-3577, Ki = 1.8 microM).

Cell Assay: Evodiamine induction of 45Ca2+ uptake was competitively antagonized by the Capsaicin antagonist Capsazepine (sc-201098). Evodiamine is described to inhibit prostaglandin E2 synthesis, cyclooxygenase-2 induction and NF-κB activation, producing antiinflammatory effects. The interferon-γ priming signal regulating the transcriptional activation of the iNOS gene is blocked by Evodiamine, suppressing iNOS protein synthesis but not affecting iNOS function. Evodiamine also demonstrates antiangiogenesis through inhibition of vascular endothelial growth factor gene expression and inhibition of the ERK 1 (p44)/ERK 2 (p42) mitogen-activated protein kinase that correlated to endothelial cell angiogenesis. Promotion of apoptosis in human leukemic U937 cells is described with Evodiamine.

Mol Cancer Ther. 2006 Sep;5(9):2398-407; J Biol Chem. 2005 Apr 29;280(17):17203-12.