Background:

Neuroblastoma, the most common solid extracranial neoplasm in children, originates from embryonic neural crest cells that usually form the sympathetic ganglia and adrenal medulla. Isobavachalcone may be applicable as an efficacious and safe drug for the treatment of neuroblastoma.
In vitro: Six chalcones from Angelica keiskei and two chalcones from Humulus lupulus L. (hop) were examined for their cytotoxicity in two human neuroblastoma cell lines (IMR-32 and NB-39) and normal cells (primary culture of rat cerebellar granule cells) by MTT assay. All chalcones exhibited cytotoxicity against neuroblastoma cells, and two of them (isobavachalcone and xanthoangelol H) had no effect on normal cells even at high concentration (10-4M) exposure. Western blot analysis showed that isobavachalcone significantly reduced pro-caspase-3 and pro-caspase-9, and subsequently increased the level of cleaved caspase-3 and cleaved caspase-9 in both neuroblastoma cell lines. Moreover, Bax was markedly induced by isobavachalcone application [1].
In vivo: After oral administration of IBC (80 mg/kg) to 6 rats, plasma con-centrations of IBC were determined by the described LC–MS/MSmethod. The mean plasma concentration–time profiles (n = 6) are deternimned. The area under the plasma concentration–timecurve (AUC) 1583.1 ng/mL h, average dwell time (MRT) 5.78 h, half-life (t1/2) 6.15 h, peak time (Tmax) 2.25 h, plasma clearance (CL/F) 9.86 L/h , apparent volume of distribution(V/F) 90.34 L, and maximum plasma concentration (Cmax) 351.2 ng/mL [2].
Clinical trial: Currently no clinical data are available.
参考文献:
[1] Nishimura R, Tabata K, Arakawa M, Ito Y, Kimura Y, Akihisa T, Nagai H, Sakuma A, Kohno H, Suzuki T. Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma. Biol Pharm Bull. 2007;30(10):1878-83.
[2] Ma T, Nie LJ, Li HM, Huo Q, Zhang YX, Wu CZ. Determination of isobavachalcone in rat plasma by LC-MS/MS and its application to a pharmacokinetic study. J Pharm Biomed Anal. 2015;107:50-5.