Study On The Mechanism Of Heart Pharmacological Safety Of The Main Components Of Yunnan Baiyao

Yunnan Baiyao is a well-known Chinese patent medicine.It has a wide range of pharmacological effects.Among them,Aconitum kusnezoffii Reichb.is a common Chinese herbal medicine with high medicinal value and strong toxicity.Studies have shown that one of the key ion targets for arrhythmia induced by aconitine,the main active ingredient in Aconitum kusnezoffii Reichb.,may be the potassium channel of hERG.However,the study on the cardiotoxicity of water extract of Aconitum kusnezoffii Reichb.is not deep enough.The blocking effect of water extract of Aconitum kusnezoffii Reichb.on potassium channel current of hERG was studied in this experiment.Panax notoginseng in Yunnan Baiyao is also a common Chinese herbal medicine.Studies have shown that Panax notoginseng saponins,the main active ingredient of Panax notogins’eng,have extensive and obvious antagonistic effects on ion channels and arrhythmia.On this basis,the effects of water extract of Panax notoginseng and several main components of Panax notoginseng saponins on potassium channel of hERG were studied,and the cardiac safety of Panax notoginseng was explored.The structure of hERG channel is special,and it is often regarded as an important target for drug cardiotoxicity.In this paper,we studied the effects of the main components of Yunnan Baiyao,namely the water extract of Radix Aconiti,the water extract of Panax notoginseng and the total saponins of Panox notoginseng,on the potassium channel of hERG in the heart,and discussed the cardiac pharmacological safety mechanism of Yunnan Baiyao.In this paper,the whole cell patch clamp technique was used to study the effects of water extract of Aconitum kusnezoffii Reichb,water extract of Panax notoginseng and several main components of total saponins of Panax notoginseng on potassium channel of hERG.Through experiments,the following conclusions are drawn1.Aqueous extract of Aconitum kusnezoffii Reichb inhibited potassium channel of hERG in a concentration-dependent manner,IC50=23.42 mg/mL2.The water extract of Panax notoginseng could enhance the potassium channel of hERG at 0.1 mg/mL.The potassium channel of hERG was not stable at 0.3 mg/mL,but inhibited at higher concentration3.10 μM ginsenoside Rbl significantly enhanced potassium channel of hERG,and 10 μM ginsenoside Rd significantly enhanced potassium channel of hERG,while 10μM ginsenoside Rgl significantly inhibited potassium channel current of hERG,while 10 notoginsenoside R1 had no significant effect on potassium channel of hERGThe effect of water extract of Panax notoginseng on potassium channel of hERG was studied.It was found that the water extract of Panax notoginseng could enhance potassium channel of hERG at lower concentration and was unstable at higher concentration.The main components of Panax notoginseng saponins have different effects on the current of hERG potassium channel at a certain concentration.Some components have an enhancement effect,some components have an inhibitory effect,and some components have no significant effect.Yunnan Baiyao contains arrhythmogenic and anti-arrhythmic medicines,Panax notoginseng.This study shows that the target of arrhythmogenic action of Panax notoginseng is the potassium channel of hERG,and a certain concentration of Panax notoginseng can enhance the potassium channel of hERG.Therefore,exploring the cardiac pharmacological safety mechanism of the two main components of Yunnan Baiyao,Aconitum kusnezoffii Reichb.and Panax notoginseng,is of great significance to the clinical application of Yunnan Baiyao and the development of new drugsIn this experiment,the effects of Panax notoginseng water extract on hERG potassium channel were studied,and it was found that the Panax notoginseng water extract enhanced hERG potassium channel at lower concentration and was unstable at higher concentration.Several main components of total saponins have different effects on the potassium channel current of hERG.Yunnan Baiyao contains arrhythmogenic drug Aconitum kusnezoffii Reichb.,and it also contains anti-arrhythmia drug Panax notoginseng,and the study in this paper shows that Aconitum kusnezoffii Reichb.has an arrhythmia target of hERG potassium ion channel,and Panax notoginseng with a certain concentration has a certain enhancement effect on hERG potassium ion channel.Therefore,it is very important to explore the cardiac pharmacological safety mechanism of the two main components of Yunnan Baiyao,namely Aconitum kusnezoffii Reichb and Panax notoginseng,for the clinical application of Yunnan Baiyao and the development of new drugs.