Cyclovirobuxine D

Cyclovirobuxine D (CVB-D) is an alkaloid, and the main active component of the traditional Chinese medicine B. microphylla, that has diverse biological activities.^1,2,3,4,5,6 It is an ether-a-go-go related gene (ERG) potassium channel blocker with an IC₅₀ value of 19.7 μM using whole-cell patch-clamp electrophysiology in HEK293 cells expressing the human receptor.¹ I_ERG blockade is activation-dependent, indicating CVB-D binds to open ERG channels. CVB-D increases the amount and rate of calcium release from intracellular stores in healthy neonatal rat cardiac myocytes and those isolated from adult rats with heart failure in a concentration-dependent manner.² It also increases expression of ryanodine receptor 2 (Ryr2) and sarcoplasmic reticulum calcium ATPase 2a (Serca2a) and decreases expression of the sodium-calcium exchanger (Ncx). In vivo, CVB-D (0.5-2.0 mg/kg) reduces mortality and improves cardiac function in a rat model of congestive heart failure.³ CVB-D pretreatment (1 mg/kg per day for 4 days) inhibits myocardial apoptosis and mitochondrial cytochrome C release induced by doxorubicin in mice.⁴ CVB-D also induces cellular autophagy and inhibits growth of MCF-7 breast cancer cells and induces mitochondrial apoptosis in MGC803 and MKN26 gastric cancer cells.^5,6

1.Zhao, J., Wang, Q., Xu, J., et al.Cyclovirobuxine D inhibits the currents of HERG potassium channels stably expressed in HEK293 cellsEur. J. Pharmacol.660(2-3)259-267(2011) 2.Yu, B., Ruan, M., Zhou, L., et al.Influence of cyclovirobuxine D on intracellular [Ca2+] regulation and the expression of the calcium cycling proteins in rat myocytesFitoterapia83(8)1653-1665(2012) 3.Yu, B., Fang, T.-H., Lü, G.-H., et al.Beneficial effect of cyclovirobuxine D on heart failure rats following myocardial infarctionFitoterapia82(6)868-877(2011) 4.Guo, Q., Guo, J., Yang, R., et al.Cyclovirobuxine D attenuates doxorubicin-induced cardiomyopathy by suppression of oxidative damage and mitochondrial biogenesis impairmentOxid. Med. Cell. Longev.2015(151972)(2015) 5.Lu, J., Sun, D., Gao, S., et al.Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cellsJ. Pharmacol. Sci.125(1)74-82(2014) 6.Wu, J., Tan, Z., Chen, J., et al.Cyclovirobuxine D inhibits cell proliferation and induces mitochondria-mediated apoptosis in human gastric cancer cellsMolecules20(11)20659-20668(2015)