从、、和中选定的多酚的抗霍乱毒素活性。

Anti-Cholera toxin activity of selected polyphenols from , , and .

机构信息

Indian Council of Medical Research - National Institute of Traditional Medicine, Belagavi, Karnataka, India.

KLE Academy of Higher Education and Research (KAHER), Belagavi, India.

出版信息

Front Cell Infect Microbiol. 2023 Apr 11;13:1106293. doi: 10.3389/fcimb.2023.1106293. eCollection 2023.

DOI:10.3389/fcimb.2023.1106293

PMID:37113136

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10126245/

Abstract

INTRODUCTION

, , 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.

METHODS

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.

RESULTS AND DISCUSSION

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.

摘要

简介

在印度， traditionally used to treat diarrheal diseases 被传统上用于治疗腹泻疾病，并且据我们早期的研究报道，它们具有抗霍乱毒素活性。由于多酚被报道可以中和霍乱毒素（CT），因此本研究使用、、方法研究了这些植物中选定的多酚对 CTB 与 GM1 受体结合的抑制活性。

方法

使用分子建模方法研究了三种植物中 20 种多酚化合物与 CT 之间的分子间相互作用，使用 DOCK6。基于分子间相互作用，选择了两种酚酸，鞣花酸（EA）和绿原酸（CHL）；两种类黄酮，芦丁（RTN）和根皮苷（PHD），以及它们各自的标准品，没食子酸（GA）和槲皮素（QRTN）。使用分子动力学模拟验证对接复合物的稳定性。此外，使用 GM1 ELISA 和 cAMP 测定法评估了六种化合物对 CT 的体外抑制活性。在 assay 中对 CT 表现出显著活性的 EA 和 CHL 被研究了其对 CT 诱导的成年小鼠液体积累和组织病理学变化的中和活性。

结果与讨论

分子建模研究表明，CT-EA、CT-CHL 和 CT-PHD 复合物的结构稳定性明显优于各自的对照物。所有选定的六种化合物均显著降低 CT 诱导的 cAMP 水平，而 EA、CHL 和 PHD 对 CT 与 GM1 的结合抑制作用>50%。在 assay 中对 CT 表现出显著中和活性的 EA 和 CHL 也显著降低了 CT 诱导的成年小鼠液体积累和组织病理学变化。我们的研究从这三种植物中鉴定出了针对 CT 诱导性腹泻的生物活性化合物。