Daurisoline

Am J Chin Med. 2010;38(1):37-49.

Daurisoline suppressed early afterdepolarizations and inhibited L-type calcium current.[Pubmed: 20128043]

Our previous studies have shown that Daurisoline (DS) exerted antiarrhythmic effects on various experimental arrhythmias. In this study, the effects of Daurisoline on early afterdepolarizations (EADs) and its possible mechanisms have been investigated. Cardiac hypertrophy was induced in rabbits by coarctating the abdominal aorta.
METHODS AND RESULTS:
The effects of Daurisoline on action potential duration (APD) and the incidences of EADs were studied in hypertrophied papillary muscles of rabbits in the conditions of low external K(+) concentration ([K(+)]o) and dofetilide (dof) by using standard microelectrode technique. The whole-cell patch clamp was used to record the L-type calcium current (I(Ca-L)) in isolated left ventricular cells of rabbits. The results showed that in hypertrophied papillary muscles of rabbits with low [K(+)]o ([K(+)]o = 2.7 mM), 1 microM dof prolonged APD(50) and APD(90) markedly and the incidence of EADs was 66.7% (4/6, p < 0.01); when 15 microM Daurisoline was applied, the incidence of EADs was 0% (0/4, p < 0.01) and the prolonged APD was shortened (p < 0.01). In a single myocyte, Daurisoline could also inhibit EADs induced by dof, low [K(+)]o and low external Mg(2+) concentration ([Mg(2+)]o) ([Mg(2+)](o) = 0.5 mM). Daurisoline could decrease the triangulation. In a single myocyte, Daurisoline could make the I-V curve upward, shift the steady-state activation curves to the right and the steady-state inactivation curves to the left and prolong the tau value of recovery curve obviously.
CONCLUSIONS:
These results suggested that Daurisoline could inhibit EADs which may be associated with its blockade effects on I(Ca-L).

Zhongguo Yao Li Xue Bao. 1996 May;17(3):248-51.

Effects of daurisoline on intracellular Ca2+ activity in myocardium.[Pubmed: 9812749]

To explain the effect of Daurisoline (DS) on delayed afterdepolarization (DAD).
METHODS AND RESULTS:
Ca(2+)-sensitive microelectrode technic was used to record intracellular Ca2+ activity (alpha Cai) and triggered activity (TA) arising from DAD in myocardium. Strophantin G 3 mumol.L-1 yielded an increase in resting myocardial alpha Cai by 0.19 +/- 0.11 mumol.L-1 and transient elevations of alpha Cai by 1.48 +/- 0.55 and 4.96 +/- 1.81 mumol.L-1, respectively during the development of DAD and TA. By pretreatment with DS or verapamil, strophantin G-caused elevations of the alpha Cai in resting and provoked myocardia were eliminated and TA disappeared. DS 50 mumol.L-1 reduced Na(+)-free medium-induced elevation of dog Purkinje fibrous alpha Cai and abolished caffeine-induced increase of dog myocardial alpha Cai.
CONCLUSIONS:
DS inhibited DAD and TA by preventing an increase of alpha Cai via transmembrane Ca2+ entry and Ca2+ release from the reticulum.

J Nat Prod. 2012 Sep 28;75(9):1539-45.

Effect of daurisoline on HERG channel electrophysiological function and protein expression.[Pubmed: 22974355]

Daurisoline (1) is a bis-benzylisoquinoline alkaloid isolated from the rhizomes of Menispermum dauricum. The antiarrhythmic effect of 1 has been demonstrated in different experimental animals.
METHODS AND RESULTS:
In previous studies, Daurisoline (1) prolonged action potential duration (APD) in a normal use-dependent manner. However, the electrophysiological mechanisms for Daurisoline-induced prolongation of APD have not been documented. In the present study, the direct effect of Daurisoline was investigated on the hERG current and the expression of mRNA and protein in human embryonic kidney 293 (HEK293) cells stably expressing the hERG channel. It was shown that Daurisoline inhibits hERG current in a concentration- and voltage-dependent manner. In the presence of 10 μM Daurisoline, steady-state inactivation of V(1/2) was shifted negatively by 15.9 mV, and Daurisoline accelerated the onset of inactivation. Blockade of hERG channels was dependent on channel opening. The expression and function of hERG were unchanged by Daurisoline at 1 and 10 μM, while hERG expression and the hERG current were decreased significantly by Daurisoline at 30 μM.
CONCLUSIONS:
These results indicate that Daurisoline, at concentrations below 30 μM, exerts a blocking effect on hERG, but does not affect the expression and function of the hERG channel. This may explain the relatively lower risk of long QT syndrome after long-term usage.

Yao Xue Xue Bao. 1998;33(3):165-70.

Effects of daurisoline and its three optical isomers on ischemic injury in cultured pheochromocytoma (PC12) cells.[Pubmed: 11938959]

In this study, the protective effects of (-)-R.R-Daurisoline and its three optical isomers on ischemic injury in cultured PC12 cells induced by treating cells with NaCN in glucose-free medium were investigated.
METHODS AND RESULTS:
Cell viability was measured using MTT assay. The results indicated that these compounds, especially (-)-S.R and (+)-R.S isomers were found substantially to attenuate ischemic injury in PC12 cells in a dose-dependent manner. The IC50 values of (-)-R.R, (-)-S.R, (+)-R.S and (+)-S.S isomers were shown to be 18.6 x 10(-6), 2.4 x 10(-6), 5.9 x 10(-6) and 90 x 10(-6) mol.L-1, respectively. Intracellular free Ca2+ concentration in PC12 cells was measured using AR-CM-MIC cation measurement system with Fura-2/AM as Ca2+ fluorescent indicator. (-)-R.R-Daurisoline and its three optical isomers: (-)-S.R, (+)-R.S and (-)-S.S were found to markedly inhibit the increase of cytosolic free Ca2+ concentration induced by NaCN (20 mmol.L-1) in a dose-dependent manner. Their IC50 were found to be 3.55 x 10(-6), 0.59 x 10(-6), 1.29 x 10(-6) and 24.3 x 10(-6) mol.L-1 respectively.
CONCLUSIONS:
It is suggested that the cytoprotective effects of Daurisoline and its isomers were mediated by blocking Ca2+ influx into cells.