Anti-Cholera toxin activity of selected polyphenols from Careya arborea , Punica granatum , and Psidium guajava

, , and are traditionally used to treat diarrheal diseases in India and were reported to show anti-Cholera toxin activity from our earlier studies. As polyphenols are reported to neutralize Cholera toxin (CT), the present study investigated the inhibitory activity of selected polyphenols from these...

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Published in:	Frontiers in cellular and infection microbiology Vol. 13; p. 1106293
Main Authors:	Charla, Rajitha, Patil, Priyanka P, Patil, Vishal S, Bhandare, Vishwambhar V, Karoshi, Veeresh, Balaganur, Venkanna, Joshi, Rajesh K, Harish, Darasaguppe R, Roy, Subarna
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 11-04-2023
Subjects:	Animals cell free culture filtrate Cellular and Infection Microbiology Cholera Cholera toxin Cholera Toxin - metabolism cytotoxicity Diarrhea - drug therapy docking G(M1) Ganglioside - metabolism GM1 ELISA Mice molecular dynamics simulations Polyphenols - pharmacology Pomegranate - metabolism Psidium - metabolism molecular dynamics simulations docking GM1 ELISA Cholera toxin cell free culture filtrate cytotoxicity
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Summary:	, , and are traditionally used to treat diarrheal diseases in India and were reported to show anti-Cholera toxin activity from our earlier studies. As polyphenols are reported to neutralize Cholera toxin (CT), the present study investigated the inhibitory activity of selected polyphenols from these plants against CTB binding to GM1 receptor using , , and approaches. Molecular modelling approach was used to investigate the intermolecular interactions of selected 20 polyphenolic compounds from three plants with CT using DOCK6. Based on intermolecular interactions, two phenolic acids, Ellagic acid (EA) and Chlorogenic acid (CHL); two flavonoids, Rutin (RTN) and Phloridzin (PHD) were selected along with their respective standards, Gallic acid (GA) and Quercetrin (QRTN). The stability of docked complexes was corroborated using molecular dynamics simulation. Furthermore, in vitro inhibitory activity of six compounds against CT was assessed using GM1 ELISA and cAMP assay. EA and CHL that showed prominent activity against CT in assays were investigated for their neutralizing activity against CT-induced fluid accumulation and histopathological changes in adult mouse. The molecular modelling study revealed significant structural stability of the CT-EA, CT-CHL, and CT-PHD complexes compared to their respective controls. All the selected six compounds significantly reduced CT-induced cAMP levels, whereas EA, CHL, and PHD exhibited > 50% binding inhibition of CT to GM1. The EA and CHL that showed prominent neutralization activity against CT from studies, also significantly decreased CT-induced fluid accumulation and histopathological changes in adult mouse. Our study identified bioactive compounds from these three plants against CT-induced diarrhea.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Antibiotic Resistance and New Antimicrobial drugs, a section of the journal Frontiers in Cellular and Infection Microbiology Reviewed by: Jorge Alberto Giron, University of Puebla, Mexico; Tooba Mahboob, University of Malaya, Malaysia Edited by: Ibrahim Bitar, Charles University, Czechia
ISSN:	2235-2988 2235-2988
DOI:	10.3389/fcimb.2023.1106293