Acta Vet. Brno 2017, 86: 223-230

The capability of minor quaternary benzophenanthridine alkaloids to inhibit TNF-α secretion and cyclooxygenase activity

Jan Hošek1, Kristýna Šebrlová2, Petra Kaucká3, Ondřej Peš2, Eva Táborská2

1University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Pharmacy, Department of Molecular Biology and Pharmaceutical Biotechnology, Brno, Czech Republic
2Masaryk University, Faculty of Medicine, Department of Biochemistry, Brno, Czech Republic
3University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Pharmacy, Department of Natural Drugs, Brno, Czech Republic

Received January 27, 2017
Accepted May 31, 2017

Quaternary benzophenanthridine alkaloids are known to have a wide range of biological effects, including antimicrobial, antifungal, anti-inflammatory, and antitumour activities. However, only sanguinarine and chelerythrine have been studied intensively. The aim of this study was to evaluate the anti-inflammatory potential of the five minor quaternary benzophenanthridine alkaloids sanguilutine, sanguirubine, chelirubine, chelilutine, and macarpine in vitro and to compare them with more thoroughly studied sanguinarine and chelerythrine. Before making cell-based assays, the cytotoxicity of the alkaloids was evaluated. The anti-inflammatory potential of the chosen alkaloids was evaluated as for their ability to modulate the lipopolysaccharide-induced secretion of tumour necrosis factor α (TNF-α) in the macrophage-like cell line THP-1. The cyclooxygenase (COX)-1 and COX-2 inhibitory activities were also measured. The results indicate that the presence of a methylenedioxy ring attached at carbon (C)7-C8 is important for reducing the secretion of TNF-α. Interestingly, this effect did not show a simple dependence on concentration. The selected alkaloids showed little or no anti-COX activity. The results obtained from the present experiments may provide additional information useful in understanding the structure-to-activity relationship of the quaternary benzophenanthridine alkaloids. The anti-inflammatory potential and the cytotoxic effect are driven by the presence of a methylenedioxy ring attached at C7-C8 and C2-C3, respectively.


Financial support of this work by IGA VFU No. 54/2014/FaF (to P.H.) and Specific University Research Grant No. MUNI/A/1205/2016 is gratefully acknowledged.


26 live references