Understanding the Anti-Diarrhoeal Properties of Incomptines A and B: Antibacterial Activity against Vibrio cholerae and Its Enterotoxin Inhibition.

Fernando Calzada,Elihu Bautista,Normand García-Hernández,Jesús Iván Solares-Pascasio,Elizabeth Barbosa,Claudia Velázquez,Sergio Hidalgo-Figueroa,Miguel Valdes

doi:10.3390/ph15020196

Abstract

Incomptines A (IA) and B (IB) are two sesquiterpene lactones with antiprotozoal, antibacterial, cytotoxic, antitumor, spermicidal, and phytotoxic properties. The antibacterial activity of IA and IB against bacteria causing diarrhoea have been reported; however, no information is available regarding their antibacterial activity on Vibrio cholerae. In this work, both compounds were evaluated for their anti-diarrhoeal potential using the bacterium V. cholerae, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) analysis on cholera toxin, and a cholera toxin-induced diarrhoea model in male Balb/c mice. In addition, a molecular docking study was carried out to understand the interaction of IA and IB with cholera toxin. In terms of antibacterial activity, IB was three times more active than IA on V. cholerae. In the case of SDS-PAGE analysis and the in silico study, IA was most effective, revealing its potential binding mode at a molecular level. In terms of anti-diarrhoeal activity, IA was 10 times more active than IB and racecadotril, an antisecretory drug used as positive control; the anti-diarrheal activity of IB was also closer than racecadotril. The results obtained from in vitro, in vivo, and computational studies on V. cholerae and cholera toxin support the potential of IA and IB as new anti-diarrhoeal compounds.

Highlights

The antibacterial activity of both sesquiterpene lactones (SLs) was superior to that of chloramphenicol (CLO), an antibiotic drug used as a positive control, which had an minimal inhibitory concentration (MIC) value > 2 mg/mL
Anti-diarrhoeal activity of the incomptine A (IA) and incomptine B (IB) were assayed on a cholera toxin-induced diarrhoea model in male
The results showed (Table 1) that IA had an inhibitory effect with an effective doses 50 (ED50) of 8.1 mg/kg; its effect was 10-fold more active than IB and racecadotril, an antisecretory drug used as the control

Summary

Introduction

Worldwide gastrointestinal infections are the most common cause of diarrhoea, and are an important cause of morbidity and mortality in developing countries. Diarrhoeal diseases (DDs) are causes of millions of deaths every year, affecting all age groups, but mainly children younger than 5 years [1,2,3,4]. In Mexico, DDs are an important health problem, and are the second greatest cause of morbidity among groups of all ages [5]. There are a wide range of pathogens that can cause DD, including enterotoxin-producing bacteria strains such as Escherichia coli, Clostridium difficile, Salmonella typhi, Yersinia enterocolitica, and Vibrio cholerae. V. cholerae causes an acute infectious diarrhea known as cholera, Pharmaceuticals 2022, 15, 196.

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