Supporting information Details on the chemical characterization of UA from C. substellata are available online at http:// www.thieme-connect.de/products ABStR AC tThe scientific interest in ( + )-usnic acid has grown because of its antitumor, cytotoxic, and antimicrobial activities as well as weight loss. However, overuse of usnic acid has been related with severe hepatotoxicity, making its use questionable. In this study, we decided to expand the knowledge of usnic acid biological activities by characterizing its effects on the mammalian myocardium as a potential pharmacological target. Usnic acid was isolated from samples of Cladonia substellata and submitted to chemical characterization. Molecular inclusion complexes of usnic acid with hydroxypropyl β-cyclodextrin were prepared to improve its water solubility. The effects of usnic acid on the atrial contractility and Ca 2 + influx were carried out in the left atrium of guinea pigs and the effect of usnic acid on the L-type Ca 2 + current was performed in rat ventricular cardiomyocytes enzymatically isolated. To evaluate the membrane integrity of cells subjected to usnic acid, we used histological procedures. Usnic acid reduced atrial contraction with an EC 50 of 43.0 ± 1.0 μM. This effect was related to a reduction of Ca 2 + entry in myocardial cells. In isolated cardiac myocytes, usnic acid at 100 μM inhibited the L-type Ca 2 + current by 73.0 %. In addition, usnic acid caused an irreversible myocardial contracture, reflecting a serious disturbance of the intracellular Ca 2 + homeostasis. Such an effect could not be ascribed to tissue death because cell membrane integrity was confirmed by histological observation. Taken together, our results show that usnic acid impairs cardiac function. Clearly more studies will be necessary to allow further applications of this natural product.
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