Annona cherimola Miller and Its Flavonoids, an Important Source of Products for the Treatment of Diabetes Mellitus: In Vivo and In Silico Evaluations

Fernando Calzada; Miguel Valdes; Jesús Martínez-Solís; Claudia Velázquez; Elizabeth Barbosa

doi:10.3390/ph16050724

Annona cherimola Miller and Its Flavonoids, an Important Source of Products for the Treatment of Diabetes Mellitus: In Vivo and In Silico Evaluations

Pharmaceuticals (Basel). 2023 May 10;16(5):724. doi: 10.3390/ph16050724.

Authors

Fernando Calzada¹, Miguel Valdes², Jesús Martínez-Solís², Claudia Velázquez³, Elizabeth Barbosa²

Affiliations

¹ Unidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades 2° Piso CORSE, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06720, Mexico.
² Instituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Plan de San Luis y Salvador Díaz Mirón S/N, Col. Casco de Santo Tomás, Miguel Hidalgo, Mexico City CP 11340, Mexico.
³ Área Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autonoma del Estado de Hidalgo, Circuito exHacienda La Concepcion s/n, Carretera Pachuca-Atocpan, San Agustin Tlaxiaca CP 42076, Mexico.

Abstract

The antihyperglycemic activity of ethanolic extract from Annona cherimola Miller (EEAch) and its products were evaluated using in vivo and in silico assays. An α-glucosidase inhibition was evaluated with oral sucrose tolerance tests (OSTT) and molecular docking studies using acarbose as the control. SGLT1 inhibition was evaluated with an oral glucose tolerance test (OGTT) and molecular docking studies using canagliflozin as the control. Among all products tested, EEAc, the aqueous residual fraction (AcRFr), rutin, and myricetin reduced the hyperglycemia in DM2 mice. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak such as the control drugs. In the molecular docking studies, rutin showed more affinity in inhibiting α-glucosidase enzymes and myricetin in inhibiting the SGLT1 cotransporter, showing ∆G values of -6.03 and -3.32 kcal/mol^-1, respectively, in α-glucosidase enzymes. In the case of the SGLT1 cotransporter, molecular docking showed ∆G values of 22.82 and -7.89 in rutin and myricetin, respectively. This research sorts in vivo and in silico pharmacological studies regarding the use of A. cherimola leaves as a source for the development of new potential antidiabetic agents for T2D control, such as flavonoids rutin and myricetin.

Keywords: Annona cherimola Miller; antihyperglycemic activity; flavonoids; in silico assays; in vivo assays.

Grants and funding

This research was supported by grants from Instituto Mexicano del Seguro Social (IMSS): FIS/IMSS/PROT/PRIO/19/110 and FIS/IMSS/PROT/G17-2/1722. Awarded to F.C.