Nigellothionins from Black Cumin (Nigella sativa L.) Seeds Demonstrate Strong Antifungal and Cytotoxic Activity.

Anna S Barashkova,Sergey K Zavriev,Victoria A Salo,Eugene A Rogozhin,Vera S Sadykova

doi:10.3390/antibiotics10020166

Abstract

High-cationic biologically active peptides of the thionins family were isolated from black cumin (Nigella sativa L.) seeds. According to their physicochemical characteristics, they were classified as representatives of the class I thionin subfamily. Novel peptides were called “Nigellothionins”, so-called because of their source plant. Thionins are described as components of plant innate immunity to environmental stress factors. Nine nigellothionins were identified in the plant in different amounts. Complete amino acid sequences were determined for three of them, and a high degree of similarity was detected. Three nigellothionins were examined for antifungal properties against collection strains. The dominant peptide, NsW2, was also examined for activity against clinical isolates of fungi. Cytotoxic activity was determined for NsW2. Nigellothionins activity against all collection strains and clinical isolates varied from absence to a value comparable to amphotericin B, which can be explained by the presence of amino acid substitutions in their sequences. Cytotoxic activity in vitro for NsW2 was detected at sub-micromolar concentrations. This has allowed us to propose an alteration of the molecular mechanism of action at different concentrations. The results obtained suggest that nigellothionins are natural compounds that can be used as antimycotic and anti-proliferative agents.

Highlights

Published: 6 February 2021Plants are subjected to a wide range of abiotic and biotic stresses and have evolved various molecular defense mechanisms
Thionins are small (~5 kDa) cationic peptides divided into five classes based on the number of cysteine residues and charge
We wereport reportaadiversity diversityofofhigh high cationic biologically active thionin peptides loHere, cationic biologically active thionin peptides localcalized in black cumin

Summary

Introduction

Published: 6 February 2021Plants are subjected to a wide range of abiotic and biotic stresses and have evolved various molecular defense mechanisms. Antimicrobial peptides (AMPs) are a part of plants’. A wide range of plant AMPs have been described and grouped into families: thionins, defensins, hevein-like, knottin-type, lipid transfer proteins, α-hairpinins, snakins, cyclotides, and some unclassified peptides [2]. Thionins were the first plant AMPs to be described. Balls et al first crystallized thionins in 1942 [3] and Okada et al described them as a “lethal toxic substance for brewing yeast” in 1970 [4]. Thionins are small (~5 kDa) cationic peptides divided into five classes based on the number of cysteine residues and charge. The sequences and secondary structures of thionins are highly conserved. The secondary structures of thionins generate a “β1-α1α2-β2-random coil” motif with the N-terminus forming the first β-sheet [5]. The spatial structure of thionins has shown a distinct capital Greek gamma letter “Γ” shape. Thionins typically have an Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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