Study On The Pharmacodynamic Material Basis Of Xinsuning Capsule Against Arrhythmia

Arrhythmia is one of the most serious diseases in the cardiovascular system.It is a common and extremely dangerous cardiovascular disease in clinical practice.Xinsuning capsule is composed of eleven Chinese medicines including Coptis,Pinellia,Poria,Citrus aurantium,Changshan,Lotus Seed Heart,Sophora flavescens,Artemisia annua,Ginseng,Ophiopogon and Licorice It is a safe and effective therapeutic drug and has no obvious side effects since it was launched on the market.Its chemical composition is complex,and the effective substances are not yet very clear.In this study,a variety of technical methods were used to qualitatively analyze the chemical components of Xinsuning capsules,and a quantitative analysis method for 16 chemical components was established.The rats were preadministrated with Xinsuning capsules,and the arrhythmia model induced by barium chloride was established.The model is used to evaluate the efficacy of Xinsuning capsules through electrocardiogram and biochemical indicators;based on serum metabolomics,the potential biological information is deeply explored and the antiarrhythmic mechanism of Xinsuning capsules is further explored.In this experiment,the volatile components,alcohol-soluble components,and watersoluble components of Xinsuning capsule were qualitatively analyzed by gas chromatography coupled to mass spectrometry(GC-MS)and liquid chromatography coupled to both mass spectrometry(LC-MS)and tandem mass spectrometry(NMR).Twenty-two volatile components were identified.A total of 22 volatile components were identified.The 59 alcoholsoluble components included 18 alkaloids,33 flavonoids,5 coumarins,2 alcoholamines and 1triterpene.By comparing with the standard,9 chemical constituents,such as sophocarpine,matrine,berberine,palmatine,liquiritigenin,etc.,were confirmed,and the mass spectrometric fragmentation rules of alkaloids and flavonoids were also summarized.A total of 10 watersoluble components were identified,including amino acids、organic acid and sugars.A rapid and quantitative analysis method for multiple components of Xinsuning capsule was established by LC-MS/MS,and the simultaneous quantitative analysis of multiple components with different contents was realized by the multiple dilution method.The results of methodological verification showed that the linear relationship of the 16 index components was good in the corresponding concentration range,and the R2 was all greater than 0.999;RSDs of precision were less than or equal to 2.06%;the repeatable RSDs were all less than or equal to 2.9%;stability RSDs were all less than or equal to 2.42%;the recoveries of the 16 compounds were in the range of 95.96%-104.73%,which proved that the method was stable and reliable.The arrhythmia model of rats was established by the method of barium chloride injection through tail vein,and the anti-arrhythmia effect of Xinsuning capsule was evaluated.ECG monitoring showed that Xinsuning capsule could significantly delay the occurrence time and duration of arrhythmia induced by barium chloride in rats(p < 0.05).Compared with the model group,Xinsuning capsule could significantly increase the Na+-K+-ATPase activity in the left ventricle of rats(p < 0.01).Serum metabolomics analysis of rats in each group showed that a total of 69 different metabolites were screened in the model group compared with the Xinsuning administration group.The relative content analysis of differential metabolites showed that Xinsuning capsule had a callback trend to 26 metabolites.Enrichment analysis of the metabolic pathways of 26 different metabolites indicated that Xinsuning capsule could improve the biosynthesis of unsaturated fatty acids and arachidonic acid metabolism.In this paper,the qualitative analysis of Xinsuning capsule was carried out by multiple analysis techniques,and the chemical composition of Xinsuning capsule was preliminarily defined.An LC-MS method for the quantitative determination of 16 chemical components was established,which provided a reference for its quality evaluation.Xinsuning capsule could significantly delay the occurrence time and shorten the duration of arrhythmia induced by barium chloride injection through tail vein.In addition,it can improve the process of arachidonic acid metabolism and the biosynthesis of unsaturated fatty acids.The mechanism of Xinsuning capsule’s anti-arrhythmia effect was preliminarily discussed.