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

Jan Hošek,Kristýna Šebrlová,Ondřej Peš,Eva Táborská,Petra Kaucká

doi:10.2754/avb201786030223

Abstract

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.

Highlights

Plants and their products have been used since the beginning of human history as remedies for various diseases and disorders
The results indicate that the presence of a methylenedioxy ring attached at carbon (C)7-C8 is important for reducing the secretion of tumour necrosis factor α (TNF-α)
The most cytotoxic compounds chelirubine (5), sanguinarine (1), and macarpine (7) contain methylenedioxy rings attached at C2-C3 and C7-C8

Summary

Introduction

Plants and their products have been used since the beginning of human history as remedies for various diseases and disorders. The richest sources of these alkaloids are considered to be Sanguinaria canadensis L., Dicranostigma lactucoides Hook F. et Thomas, Chelidonium majus L., Macleaya cordata (Willd.) R.Br, Macleaya microcarpa (Maxim.) Fedde, Stylophorum lasiocarpum (Oliv.) Fedde, and a few species of the genus Bocconia All of these species belong to the family Papaveraceae (Dostal and Potacek 1990). 1946/1, 612 42 Brno sanguinarine and chelerythrine and the minor ones chelirubine, sanguirubine, chelilutine, sanguilutine, and macarpine have been found in these plants (Suchomelova et al 2007; Šimánek et al 2003; Slaninova et al 2014; Sebrlova et al 2015). The protective effect of chelerythrine on an ethanol-induced gastric ulcer in mice has been described recently (Li et al 2014a) It significantly reduced the gastric ulcer index, myeloperoxidase activities, and macroscopic and histological score in a dose-dependent manner

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