Combined Gamma Conglutin and Lupanine Treatment Exhibits In Vivo an Enhanced Antidiabetic Effect by Modulating the Liver Gene Expression Profile

Paloma Lucía Guerra-Ávila; Tereso J Guzmán; José Alfredo Domínguez-Rosales; Pedro Macedonio García-López; Alejandra Beatriz Cervantes-Garduño; Michael Wink; Carmen Magdalena Gurrola-Díaz

doi:10.3390/ph16010117

Combined Gamma Conglutin and Lupanine Treatment Exhibits In Vivo an Enhanced Antidiabetic Effect by Modulating the Liver Gene Expression Profile

Pharmaceuticals (Basel). 2023 Jan 13;16(1):117. doi: 10.3390/ph16010117.

Authors

Paloma Lucía Guerra-Ávila¹, Tereso J Guzmán^{1

2}, José Alfredo Domínguez-Rosales¹, Pedro Macedonio García-López³, Alejandra Beatriz Cervantes-Garduño⁴, Michael Wink⁵, Carmen Magdalena Gurrola-Díaz¹

Affiliations

¹ Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Instituto Transdisciplinar de Investigación e Innovación en Salud, Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, Guadalajara 44350, Jalisco, Mexico.
² Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstraße 48, 48149 Münster, Germany.
³ Laboratorio de Productos Bióticos, Departamento de Botánica y Zoología, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Carretera Guadalajara-Nogales Km. 15.5, Las Agujas, Zapopan 44171, Jalisco, Mexico.
⁴ Laboratorio de Genómica Clínica, Facultad de Odontología, Universidad Nacional Autónoma de México, Coyoacán, Mexico City 04510, Jalisco, Mexico.
⁵ Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany.

Abstract

Previous studies have individually shown the antidiabetic potential of gamma conglutin (Cγ) and lupanine from lupins. Until now, the influence of combining both compounds and the effective dose of the combination have not been assessed. Moreover, the resulting gene expression profile from this novel combination remains to be explored. Therefore, we aimed to evaluate different dose combinations of Cγ and lupanine by the oral glucose tolerance test (OGTT) to identify the higher antidiabetic effect on a T2D rat model. Later, we administered the selected dose combination during a week. Lastly, we evaluated biochemical parameters and liver gene expression profile using DNA microarrays and bioinformatic analysis. We found that the combination of 28 mg/kg BW Cγ + 20 mg/kg BW lupanine significantly reduced glycemia and lipid levels. Moreover, this treatment positively influenced the expression of Pdk4, G6pc, Foxo1, Foxo3, Ppargc1a, Serpine1, Myc, Slc37a4, Irs2, and Igfbp1 genes. The biological processes associated with these genes are oxidative stress, apoptosis regulation, and glucose and fatty-acid homeostasis. For the first time, we report the beneficial in vivo effect of the combination of two functional lupin compounds. Nevertheless, further studies are needed to investigate the pharmacokinetics and pharmacodynamics of the Cγ + lupanine combined treatment.

Keywords: Lupinus albus; affymetrix microarray; high-fat diet plus streptozotocin; plant proteins; quinolizidine alkaloids; type 2 rat diabetes (T2D).

Grants and funding

This work was supported by the Fondo de Desarrollo Científico de Jalisco para Atender Problemas Estatales 2019, Consejo Estatal de Ciencia y Tecnología de Jalisco (FODECIJAL, COECYTJAL) under Grant (8103-2019) to C.M.G.-D. and by the Coordinación General de Investigación, Posgrado y Vinculación Universidad de Guadalajara, under Grants (REC/0964/2019, REC/663/2020, PFICyLI-2021, and PFICyLI-2022). The first author (P.L.G.-Á.) received a fellowship from CONACyT (CVU 711223).