The antiarrhythmic effects of lavandulifolioside and ferulic acid from Leonurus cardiaca extracts on cardiac electrophysiology

Coronary heart disease, cardiac dysrhythmia and arterial hypertension are an important and increasing health problem in European countries. However, the application of several synthetic drugs is often limited by their adverse reactions and unwanted cardiovascular effects, especially in combination with further antiarrhythmic agents. Therefore, the research, development and use of new potential therapeutic agents of natural origin for cardiovascular diseases are essential.

Recently, aqueous preparations of Leonurus cardiaca (Ph. Eur.) – such as a newly developed refined extract – were reported to exert a series of effects on cardiac electrophysiology, such as I _Ca.L blockade, a reduction of the repolarising current I _K.r, as well as the prolongation of both AP-duration and the activation time constant of the I _f current, while I _Na was strikingly unaffected. This synergistic action on multiple electrophysiological targets may limit potential adverse effects, especially the risk of proarrhythmia, and is thus in accordance with the traditional use of this medicinal plant as an antianginal in European herbalism. Therefore, several extract samples were examined for substances potentially contributing to these pharmacological activities. Whereas just a few reports of pharmacological actions on the cardiovascular system have been reported for lavandulifolioside and ferulic acid, both enriched in the refined extract, in the present work these isolated constituents were examined first for specific molecular pharmacological actions on cardiac ion channels. In subsequent voltage clamp experiments carried out according to a protocol previously developed in our group, lavandulifolioside at concentration of 10µM and ferulic acid at concentration of 3µM influence neonatal rat ventricular cardiomyocytes by I _Ca.L blockade and AP-duration shortening, while I _Na was not affected. Epicardial mapping experiments on isolated rabbit hearts perfused according to the Langendorff technique showed after application of ferulic acid an increase of basic cycle length as well as a reduction of left ventricular pressure. Our in vitro investigations clearly demonstrate that lavandulifolioside and ferulic acid essentially contribute to the observed cardiac effects of L. cardiaca, according to a 'multi-component/multi-target' active principle.