Embelin is a cell-permeable benzoquinone compound that exhibits antitumor properties. Specifically antagonizes XIAP-mediated inhibition of caspase-9 activation by directly targeting the Smac and caspase-9 binding domain BIR3 (IC50 = 4.1 uM in a competitive binding assay with Smac peptide). IC50 value: 4.1 uM [1] Target: XIAP in vitro: Embelin induced activation of caspase-9 and embelin-induced apoptosis was prevented by caspase inhibitors [2]. Treatment with subtoxic doses of Embelin broadly sensitized malignant glioma cells to TRAIL-mediated apoptosis. Notably, human astrocytes were not significantly affected by the combined treatment consisting of Embelin and TRAIL. Combined treatment with Embelin and TRAIL augmented the activation of initiator caspases-8/-9 and effector caspases-3/-7, respectively [3]. in vivo: Embelin inhibited topical edema in the mouse ear, leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase activity, and various histopathological indicators. Furthermore, embelin was effective at reducing inflammatory damage induced by chronic TPA exposure [4]. Embelin (10, 30 or 50mg/kg body weight) was administrated daily per oral route for 7days. Embelin significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. Embelin administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size [5].

• [1]. Siegel C, et al. miR-23a regulation of X-linked inhibitor of apoptosis (XIAP) contributes to sex differences in the response to cerebral ischemia. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11662-7.

  [2]. Hu R, et al. Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells. Med Oncol. 2011 Dec;28(4):1584-8.

  [3]. Siegelin MD, et al. The XIAP inhibitor Embelin enhances TRAIL-mediated apoptosis in malignant glioma cells by down-regulation of the short isoform of FLIP. Neurochem Int. 2009 Nov;55(6):423-30.

  [4]. Kalyan Kumar G, et al. Embelin reduces cutaneous TNF-α level and ameliorates skin edema in acute and chronic model of skin inflammation in mice. Eur J Pharmacol. 2011 Jul 15;662(1-3):63-9.

  [5]. Kumar G K, et al. Embelin ameliorates dextran sodium sulfate-induced colitis in mice. Int Immunopharmacol. 2011 Jun;11(6):724-31.

  [6]. Xue Z, et al. Embelin suppresses dendritic cell functions and limits autoimmune encephalomyelitis through the TGF-β/β-catenin and STAT3 signaling pathways. Mol Neurobiol. 2014 Apr;49(2):1087-101.