2. Academic Validation
  3. Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development

  • J Nat Prod. 2020 Dec 24;83(12):3671-3680. doi: 10.1021/acs.jnatprod.0c00892.
José Antonio Velázquez-Domínguez 1,  Verónica Ivonne Hernández-Ramírez 1,  Fernando Calzada 2,  Luis Varela-Rodríguez 1,  Diana L Pichardo-Hernández 1,  Elihú Bautista 3,  Mayra Herrera-Martínez 4,  Rodrigo D Castellanos-Mijangos 5,  Audifas Salvador Matus-Meza 6,  Bibiana Chávez-Munguía 1,  Patricia Talamás-Rohana 1
Affiliations

Affiliations

  • 1 Departamento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, Av. IPN 2508, San Pedro Zacatenco, 07360, CDMX, México.
  • 2 Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, CMN-Siglo XXI, Av. Cuauhtémoc 330, Col. Doctores, 06720, CDMX, México.
  • 3 Unidad de Ciencias Ambientales, IPICYT, Camino a la Presa San José, No. 2055, Lomas 4a. Sección, 78216, San Luis Potosí, S.L.P., México.
  • 4 Instituto de Farmacobiología, Universidad de la Cañada, Carretera Teotitlán San Antonio Nanahuatipán Km 1.7 s/n. Paraje Titlacuatitla, 68540, Teotitlán de Flores Magón, Oax., México.
  • 5 Servicio de Imagenología Diagnóstica, Centro Médico ISSEMyM "Arturo Montiel Rojas", Av. Baja Velocidad No. 284, Carretera México-Toluca Km. 57.5, San Jerónimo Chicahualco, 52170, Metepec, Edo. Méx., México.
  • 6 Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Mexico City, CDMX, México.
PMID: 33231455 DOI: 10.1021/acs.jnatprod.0c00892
Abstract

Linearolactone (1) and kaempferol (2) have amebicidal activity in in vitro studies. The type of cell death induced by 1 and 2 and their effects on the virulence of E. histolytica were analyzed by transmission and confocal electron microscopy, Reactive Oxygen Species (ROS) production, and Apoptosis, detected by flow cytometry with dichlorofluorescein 2',7'-diacetate and annexin-V binding, respectively, and confirmed by TUNEL. The interaction of 1 and 2 with actin was analyzed by docking, and the in vivo amoebicidal activity was established with the Mesocricetus auratus model; amebic liver abscess (ALA) development was evaluated by magnetic resonance (MR) and validated post mortem. In vitro, compounds 1 and 2 caused chromatin condensation, intracellular ROS, and loss of actin structures. Coupling analysis showed that they bind to the allosteric and catalytic sites of actin with binding energies of -11.30 and -8.45 kcal/mol, respectively. Treatments with 1 and 2 induced a decrease in ALA formation without toxic effects on the liver and kidney. Thus, compound 1, but not 2, was able to induce apoptosis-like effects in E. histolytica trophozoites by intracellular production of ROS that affected the actin Cytoskeleton structuration. In vivo, compound 1 was more active than compound 2 to reduce the development of ALA.

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