Selective Anti-Giardial Action of Indirubin: Biochemical and Functional Evidence for Inhibition of Triosephosphate Isomerase and Aldose Reductase in Giardia lamblia
Por:
Flores-López L.A., López-Herrera G., Martínez-Pérez Y., Matadamas-Ortiz E.J., Gómez-Manzo S., Hernández-Alcántara G., González-Maciel A., Reynoso-Robles R., Hernández-Ochoa B., Chino-Ríos L., González-Gómez D., Arteaga-Padilla L.V., Enríquez-Flores S., De la Mora-De la Mora I.
Publicada:
1 ene 2026
Ahead of Print:
1 may 2026
Resumen:
© 2026 by the authors.The emergence of clinical resistance to conventional antigiardials underscores the need for compounds with novel mechanisms of action. This study demonstrates that indirubin exerts antigiardial activity by targeting important metabolic enzymes in Giardia lamblia. Indirubin induced a concentration-dependent decrease in trophozoite proliferation and viability, correlating with reduced activity of native triosephosphate isomerase and aldose reductase. Using recombinant enzymes, indirubin directly inhibited triosephosphate isomerase and aldose reductase, with the parasite enzymes showing greater susceptibility than their human orthologs. Structural and computational analyses suggest preferential binding of indirubin at the dimer interface of triosephosphate isomerase and within the NADP(H)-binding pocket of aldose reductase. The dual enzymatic inhibition was concordant with methylglyoxal accumulation, extensive protein carbonylation, and the formation of advanced glycation end products. These effects culminated in apoptotic-like death and severe ultrastructural damage, including alteration of the adhesive disc and microtubule networks. By targeting vulnerabilities in the metabolic and redox pathways of G. lamblia through a multifactorial mechanism distinct from current therapies, our findings support indirubin as a promising candidate for the treatment of giardiasis.
Filiaciones:
Laboratorio de Biomoléculas y Salud Infantil, SECIHTI—Instituto Nacional de Pediatría, Mexico City 04530, Mexico
Laboratorio de Inmunodeficiencias Primarias, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Mexico City 14380, Mexico
Laboratorio de Investigación de Agro-Recursos y Metabolitos Secundarios, Universidad Autónoma Chapingo, Texcoco 56230, Mexico
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Laboratorio Morfología Celular y Tisular, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
Laboratorio de Investigación en Ciencias Ómicas y Epidemiología Microbiana, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, 06720, Mexico
Posgrado en Ciencias Biológicas (Maestría), Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Laboratorio de Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
Licenciatura en Bioquímica Diagnóstica, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
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