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Drug-induced cardiotoxicity is a serious concern in recent years, and acquired long QT syndrome (LQTS) is an important manifestation of cardiotoxicity. hERG gene encodes the α subunit of the rapidly activated delayed rectifier potassium channel (Ikr), which plays an important role in action potential phase 3 repolarization. Drug inhibition of Ikr/hERG channel leads to prolonged QT interval, accompanied by Tdp malignant arrhythmia, which can cause sudden death. We studied the effect of berberines on the hERG K+ channels after combination with rosuvastatin and glibenclamide, and evaluated the cardiac safety of these drugs in combination. Whole cell patch clamp technique was used to detect the effect of the combinations of these drugs on hERG current on HEK293 cells stably expressing hERG gene. The results showed that the inhibitory effects of berberine or dihydroberberberine combined with rosuvastatin on hERG current were higher than single drug (P < 0.05), but the combination had no effect on the kinetics of hERG channel. Berberine or dihydroberberberine combined with glibenclamide had higher inhibitory effects on hERG current than the application of single drug (P < 0.05) while the time constant of hERG channel inactivation was shortened after the combination (P < 0.05). In addition, the combination of berberine and glibenclamide inhibited hERG channel activation (P < 0.05). In conclusion, our results demonstrated that the combination of berberine with rosuvastatin or glibenclamide significantly inhibited hERG current and the inhibition effects were higher than the application alone. Therefore, when the two drugs that have inhibitory effects on the hERG channel are combined, the risk of inducing prolonged QT interval is significantly increased, and therefore reducing cardiac safety.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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