Biliatresone

Biliatresone is a natural toxin isolated from Dysphania glomulifera and D. littoralis. Biliatresone, a 1,2-diaryl-2-propenone class of isoflavonoid, produces extrahepatic biliary atresia in a zebrafish model[1].

Biliatresone has a reduction in primary cilia and a dose-dependent decrease in visible microtubules, suggesting that Biliatresone decreases microtubule stability in primary neonatal mouse extrahepatic cholangiocytes[1]. Biliatresone (2 µg/ml; for 24 hours) shows disruption of the spheroid lumen and abnormal cholangiocyte polarity in mouse cholangiocyte[1].

Biliatresone exhibits toxicity at doses of 0.065-1.0 μg/mL with a marked reduction and the lethal dose of Biliatresone in a zebrafish assay is 1 μg/mL[1]. Larvae treated at 5 dpf with low doses of biliatresone [0.0625 µg/ml (0.2 µM) and 0.125 µg/ml (0.4 µM)] shows only subtle gallbladder defects, whereas larvae treated with higher doses has pronounced morphological defects of the gallbladder and extrahepatic ducts[1].

[1]. Kyung A Koo, et al. Biliatresone, a Reactive Natural Toxin From Dysphania Glomulifera and D. Littoralis: Discovery of the Toxic Moiety 1,2-Diaryl-2-Propenone. Chem Res Toxicol. 2015 Aug 17;28(8):1519-21. [2]. Kristin Lorent, et al. Identification of a Plant Isoflavonoid That Causes Biliary Atresia. Sci Transl Med. 2015 May 6;7(286):286ra67.