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Planta Medica International Open 2017; 4(02): e59-e65
DOI: 10.1055/s-0043-114423
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

(+)-Usnic Acid Isolated from the Lichen Cladonia substellata Impairs Myocardial Contractility

Sílvia Caroline Santos Mendonça
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
,
Carla Maria Lins de Vasconcelos
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
,
Jader Santos Cruz
2   Laboratory of Excitable Membranes and Cardiovascular Biology, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
,
Danilo Roman-Campos
3   Biomedical Sciences Building, Laboratory of Electrophysiology, Federal University of São Paulo, Sao Paulo, Brazil
,
José Evaldo Rodrigues Menezes-Filho
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
,
Robson Araújo Anjos-Neto
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
,
Diogo Lucas Campos Martins
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
,
Adriano Antunes de Souza Araújo
4   Laboratory for Pharmaceutical and Toxicology Studies, Department of Pharmacy, Federal University of Sergipe, Aracaju, Brazil
,
Luiz Carlos Cides da Silva
5   Thermal Analysis Laboratory, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil
,
Marília dos Santos Bezerra
4   Laboratory for Pharmaceutical and Toxicology Studies, Department of Pharmacy, Federal University of Sergipe, Aracaju, Brazil
,
Ricardo Luiz Cavalcanti de Albuquerque-Júnior
6   Laboratory of Morphology and Structural Biology, University Tiradentes, Aracaju, Brazil
,
Eduardo Antonio Conde-Garcia
1   Cardiobiophysics Research Laboratory, Department of Physiology, Federal University of Sergipe, Aracaju, SE, Brazil
› Author Affiliations
Further Information

Publication History

received 16 August 2016
revised 30 April 2017

accepted 18 May 2017

Publication Date:
20 July 2017 (online)

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Abstract

The 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 Ca2+ influx were carried out in the left atrium of guinea pigs and the effect of usnic acid on the L-type Ca2+ 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 EC50 of 43.0±1.0 μM. This effect was related to a reduction of Ca2+ entry in myocardial cells. In isolated cardiac myocytes, usnic acid at 100 μM inhibited the L-type Ca2+ current by 73.0%. In addition, usnic acid caused an irreversible myocardial contracture, reflecting a serious disturbance of the intracellular Ca2+ 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.

Key words

Cladonia substellata - Cladoniaceae - usnic acid - lichen - heart function - Ca2+ currents

Supporting Information

    Details on the chemical characterization of UA from C. substellata are available online at http://www.thieme-connect.de/products
  • Supporting Information
 

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