Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant properties and mediates apoptosis. IC50 Value: 6.2 - 9.8 ug/mL(sarcoma cells viability)[3] Target: Apoptosis inducer in vitro: Costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affecting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen-activated protein kinase and NF-κB pathways. However, costunolide suppressed nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression via inhibition of c-Fos transcriptional activity without affecting RANKL-induced c-Fos expression. The inhibitory effects ofcostunolide were rescued by overexpression of constitutively active (CA)-NFATc1 [1]. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP [2]. Both costunolide and dehydrocostus lactone inhibited cell viability dose- and time-dependently. IC50 values ranged from 6.2 ug/mL to 9.8 ug/mL. Cells treated with costunolide showed no changes in cell cycle, little in caspase 3/7 activity, and low levels of cleaved caspase-3 after 24 and 48 h [3]. in vivo: Neither costunolide nor alpha-MGBL affected the blood-ethanol elevation in pylorus-ligated rats or that induced by intraperitoneal and intraduodenal ethanol administration [4]. Costunolide and alpha-MGBL suppressed gastric emptying in rats given 20% ethanol and 1% sodium carboxymethyl cellulose. Clinical trial:

• [1]. Cheon YH, Song MJ, Kim JY, Costunolide Inhibits Osteoclast Differentiation by Suppressing c-Fos Transcriptional Activity. Phytother Res. 2013 Jul 6.

  [2]. Rasul A, Bao R, Malhi M, Induction of apoptosis by costunolide in bladder cancer cells is mediated through ROS generation and mitochondrial dysfunction. Molecules. 2013 Jan 24;18(2):1418-33.

  [3]. Kretschmer N, Rinner B, Stuendl N, Effect of costunolide and dehydrocostus lactone on cell cycle, apoptosis, and ABC transporter expression in human soft tissue sarcoma cells. Planta Med. 2012 Nov;78(16):1749-56.

  [4]. Matsuda H, Shimoda H, Ninomiya K, Inhibitory mechanism of costunolide, a sesquiterpene lactone isolated from Laurus nobilis, on blood-ethanol elevation in rats: involvement of inhibition of gastric emptying and increase in gastric juice secretion. Alcohol