Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells

Abstract

Aim: Allocryptopine (ALL) is an alkaloid extracted from corydalis decumbens (Thunb) Pers Papaveraceae, whereas benzyltetrahydropalmatine (BTHP) is a derivative of tetrahydropalmatine extracted from corydalis ambigua (Pall) Cham et Schlecht. The aim of this study was to investigate the effects of ALL and BTHP on the human ether-a-go-go related gene (hERG) current expressed in HEK293 cells. Methods: Cultured HEK293 cells were transiently transfected with hERG channel cDNA plasmid pcDNA3.1 using Lipofectamine. The whole-cell current IHERG was evoked and recorded using Axon MultiClamp 700B amplifier. The drugs were applied via supserfusion. Results: Both ALL and BTHP reversibly suppressed the amplitude and density of I HERG in concentration-and voltage-dependent manners (the respective IC 50 value was 49.65 and 22.38 μmol/L). BTHP (30 μmol/L) caused a significant negative shift of the steady-state inactivation curve of I HERG , while ALL (30 μmol/L) did not affect the steady-state inactivation of I HERG . Furthermore, BTHP, but not ALL, shortened the time constants of fast inactivation and slow time constants of deactivation of I HERG . But both the drugs markedly lengthened the time constants for recovery of I HERG from inactivation. Using action potential waveform pulses, it was found that both the drugs at 30 μmol/L significantly suppressed the current densities in the late phase of action potential, but did not significantly affect the current densities in the early phase of action potential. Conclusion: Both ALL and BTHP derived from Chinese herbs potently block hERG current.

Novel Bayesian classification models for predicting compounds blocking hERG potassium channels

“…Therefore, it is necessary to measure the hERG inhibition activity of candidate compounds during drug discovery. Many experimental assays have been used to detect hERG blockage, such as patch clamp assays, radioligand binding assays, and fluorescence-based assays [6] . However, these assays are time-consuming, labor-intensive and costly.…”

Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R. Br.

“…In particular, analgesia is often an important consideration in developing anti-inflammatory drugs. PRO and ALL have been found to modulate dopamine receptors and sodium and potassium channels to exert analgesic effects (92)(93)(94). Therefore, ALL and PRO have good potential for development as antiinflammatory agents.…”

Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing5-HT3ARand5-HT3B

“…The voltage clamp mode of the Axon MultiClamp 700B (Molecular Devices, Sunnyvale, CA, USA) was used in this experiment [ 28 ]. The clamp voltage was −70 mV, the frequency of the Bessel filter was 2.9 kHz, and the sampling frequency was 20 kHz.…”