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

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Venkanna Balaganur¹  Veeresh Karoshi²  Darasaguppe R. Harish²  Rajesh K. Joshi²  Subarna Roy²  Vishwambhar V. Bhandare³  Vishal S. Patil⁴  Priyanka P. Patil⁴  Rajitha Charla⁴ 

[1] Indian Council of Agricultural Research – Krishi Vigyan Kendra, Bagalkot, Karnataka, India;University of Agricultural Sciences, Dharwad, Karnataka, India;Indian Council of Medical Research - National Institute of Traditional Medicine, Belagavi, Karnataka, India;Indian Council of Medical Research - National Institute of Traditional Medicine, Belagavi, Karnataka, India;Department of Microbiology, Shivaji University, Kolhapur, India;Indian Council of Medical Research - National Institute of Traditional Medicine, Belagavi, Karnataka, India;KLE Academy of Higher Education and Research (KAHER), Belagavi, India;

关键词: cell free culture filtrate;    Cholera toxin;    cytotoxicity;    docking;    GM1 ELISA;    molecular dynamics simulations;   

DOI  :  10.3389/fcimb.2023.1106293

 received in 2022-11-23, accepted in 2023-02-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCareya arborea, Punica granatum, and Psidium guajava 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 in silico, in vitro, and in vivo approaches.MethodsMolecular 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 in vitro assays were investigated for their neutralizing activity against CT-induced fluid accumulation and histopathological changes in adult mouse.Results and discussionThe 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 in vitro 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.

【 授权许可】

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Copyright © 2023 Charla, Patil, Patil, Bhandare, Karoshi, Balaganur, Joshi, Harish and Roy