Virtual screening, molecular dynamics simulations, and in vitro analysis of Sophora flavescens-derived aloperine against Haemonchus contortus.

IF 2.9 2区农林科学 Q1 VETERINARY SCIENCES

Frontiers in Veterinary Science Pub Date : 2025-06-19 eCollection Date: 2025-01-01 DOI:10.3389/fvets.2025.1620324

Anben Li, Yan Ma, Wenxi Li, Bintao Zhai, Nana Fu, Jun Li, Qianyu Zhou, Yang Liu

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引用次数: 0

Abstract

Introduction: The resistance of Haemonchus contortus to ivermectin (IVM) poses a significant economic threat to the global livestock industry. This necessitates alternative strategies for managing the development of drug resistance in H. contortus.

Methods: This study employed molecular docking screening, molecular dynamics simulations, and in vitro experiments to evaluate the effects of bioactive alkaloids from Sophora alopecuroides L. on H. contortus.

Results: Molecular docking and dynamics simulations revealed aloperine (ALO)'s strong binding affinity (-6.83 kcal/mol) and stable interaction with HC-Pgp among 13 tested alkaloids. Further evaluation through larval development test (LDT), larval migration inhibition test (LMIT), and scanning electron microscopy revealed that the combined administration of ALO and IVM exerted significantly enhanced inhibitory effects on the development, motility, and morphological integrity of IVM-resistant strains compared to monotherapy groups. Furthermore, the Rhodamine-123 accumulation assay demonstrated that aloperine significantly inhibited HC-Pgp activity (p < 0.05).

Discussion: This study provides new perspectives for exploring the natural product ALO as an anthelmintic, HC-Pgp inhibitor, and synergist molecule. Further studies evaluating in vivo safety and pharmacokinetic interactions are required to validate these findings.

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苦参碱抗弯血螨的虚拟筛选、分子动力学模拟及体外分析。

扭曲血蜱对伊维菌素（IVM）的耐药性对全球畜牧业构成重大的经济威胁。这就需要有其他的策略来管理弯曲菌的耐药性发展。方法：采用分子对接筛选、分子动力学模拟和体外实验等方法，研究苦豆子生物碱对东番莲的作用。结果：分子对接和动力学模拟表明，在13种被测生物碱中，aloperine （ALO）具有较强的结合亲和力（-6.83 kcal/mol），与HC-Pgp具有稳定的相互作用。通过幼虫发育试验（LDT）、幼虫迁移抑制试验（LMIT）和扫描电镜进一步评价显示，与单一治疗组相比，ALO和IVM联合给药对IVM耐药菌株的发育、运动和形态完整性的抑制作用显著增强。此外，罗丹明-123积累试验表明，aloperine显著抑制HC-Pgp活性（p ）。讨论：本研究为探索天然产物ALO作为驱虫药、HC-Pgp抑制剂和增效分子提供了新的视角。需要进一步研究评估体内安全性和药代动力学相互作用来验证这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Veterinary Science Veterinary-General Veterinary

CiteScore

4.80

自引率

9.40%

发文量

1870

审稿时长

14 weeks

期刊介绍： Frontiers in Veterinary Science is a global, peer-reviewed, Open Access journal that bridges animal and human health, brings a comparative approach to medical and surgical challenges, and advances innovative biotechnology and therapy. Veterinary research today is interdisciplinary, collaborative, and socially relevant, transforming how we understand and investigate animal health and disease. Fundamental research in emerging infectious diseases, predictive genomics, stem cell therapy, and translational modelling is grounded within the integrative social context of public and environmental health, wildlife conservation, novel biomarkers, societal well-being, and cutting-edge clinical practice and specialization. Frontiers in Veterinary Science brings a 21st-century approach—networked, collaborative, and Open Access—to communicate this progress and innovation to both the specialist and to the wider audience of readers in the field. Frontiers in Veterinary Science publishes articles on outstanding discoveries across a wide spectrum of translational, foundational, and clinical research. The journal''s mission is to bring all relevant veterinary sciences together on a single platform with the goal of improving animal and human health.