Kaempferol activity on Cryptosporidium parvum infection in an experimentally infected immunocompromised mouse model: In silico and in vivo investigations

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Wakid M.H.; El-Wakil E.S.; Alsulami M.N.; Azab H.

Journal: Pharmaceutical Biology

Publisher: Taylor and Francis Ltd.

Publication Date: 19 December 2025

Volume / Issue: Volume 64 / Issue 1

Pages: 27–45

ISSN: 13880209

DOI: 10.1080/13880209.2025.2603384

Scopus: View on Scopus

PubMed: 41414827

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Wakid M.H., Department of Medical Laboratory Sciences, King Abdulaziz University, Jeddah, Saudi Arabia, Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; El-Wakil E.S., Department of Parasitology, Theodor Bilharz Research Institute, Giza, Egypt; Alsulami M.N., Department of Biological Sciences, College of Science, University of Jeddah, Jeddah, Saudi Arabia; Azab H., Department of Medical Parasitology, Misr University for Science and Technology, Egypt

Abstract

Context: No vaccine or effective therapy for cryptosporidiosis currently exists, except for nitazoxanide (NTZ), which has limited effectiveness in immunocompromised hosts. Kaempferol (KPF), a naturally occurring flavonoid, has various pharmacological effects and promising antiparasitic properties. Objective: The current work aimed to examine the impact of KPF compared with NTZ on Cryptosporidium parvum (C. parvum) using both in silico molecular docking and in vivo studies with an experimentally infected immunocompromised mouse model. Materials and methods: The present study utilized KPF and NTZ as multi-target ligands to predict, determine, and evaluate their in silico target-interacted forms, thereby demonstrating their therapeutic properties against C. parvum. Mice were immunosuppressed and divided into six groups: DEXA, Model, KPF as prophylaxis, treatment with KPF, NTZ, and a combination of KPF and NTZ. Treatment efficacy was assessed through parasitological, histopathological examination, and immunohistochemical analysis of intestinal tissues using NLRP3 protein. Results: The in silico findings supported the use of KPF and NTZ as inhibitors of C. parvum growth by blocking the action of C. parvum choline and pyruvate kinases. The in vivo study demonstrated that KPF exhibits anti-cryptosporidial efficacy, particularly when combined with NTZ. The KPF+NTZ had the best results, as evidenced by a significant decrease (p < 0.001) in oocyst shedding of 83%, improved intestinal histological damage, and inhibition of the NLRP3 inflammasome pathway. Discussion and conclusion: KPF demonstrated the potential to mitigate the consequences of cryptosporidiosis and serve as an adjuvant agent to NTZ by reducing the oocyst burden, alleviating intestinal inflammation, and facilitating mucosal repair. © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

Cryptosporidium parvum; in silico molecular docking; kaempferol; mice; nitazoxanide; Animals; Antiparasitic Agents; Computer Simulation; Cryptosporidiosis; Disease Models, Animal; Female; Immunocompromised Host; Kaempferols; Molecular Docking Simulation; Nitro Compounds; Thiazoles; antiparasitic agent; choline; dimethyl sulfoxide; flavonoid; inflammasome; pyruvate kinase; pyruvic acid; kaempferol derivative; nitro derivative; thiazole derivative; animal experiment; animal model; animal tissue; Article; binding affinity; bioinformatics; controlled study; drug efficacy; enzyme linked immunosorbent assay; flow cytometry; IC50; immunocompromised patient; in silico design; in vitro study; in vivo study; inflammation; intestine tissue; male; molecular docking; molecular dynamics; mouse; nonhuman; oocyst; animal; comparative study; disease model; drug effect; drug therapy; immunology; parasitology

Citation Information

Scopus Citations: 1

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