Ruellia tuberosa compounds as type 2 diabetes mellitus inhibitors

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 4, pp. 735-747, Jul-Aug 2024. DOI: https://doi.org/10.56499/jppres23.1891_12.4.735 Original Article In silico studies of Ruellia tuberosa L. compounds as aldose reductase, dipeptidyl peptidase 4, and α-glucosidase inhibitors against type 2 diabetes mellitus [Estudios in silico de compuestos de Ruellia tuberosa L. como inhibidores de la aldosa reductasa, dipeptidil peptidasa … Continue reading Ruellia tuberosa compounds as type 2 diabetes mellitus inhibitors

J. Pharm. Pharmacogn. Res., vol. 12, no. 4, pp. 735-747, Jul-Aug 2024.

DOI: https://doi.org/10.56499/jppres23.1891_12.4.735

Original Article

In silico studies of Ruellia tuberosa L. compounds as aldose reductase, dipeptidyl peptidase 4, and α-glucosidase inhibitors against type 2 diabetes mellitus

[Estudios in silico de compuestos de Ruellia tuberosa L. como inhibidores de la aldosa reductasa, dipeptidil peptidasa 4 y α-glucosidasa contra la diabetes mellitus de tipo 2]

Ekowati Retnaningtyas1*, Andri Setiawan2, Budi Susatia1, Tanto Hariyanto3, Ni Luh Putu Eka Sudiwati3

1Department of Nursing, Malang State Health Polytechnic, Ministry of Health Indonesia, Malang, 65119, Indonesia.

2Master Program of Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang 65145, Indonesia.

3Department of Blood Bank Technology, Malang State Health Polytechnic, Ministry of Health Indonesia, Malang, 65119, Indonesia.

*E-mail: ekowati.poltekes@gmail.com, andre.bbc4088@gmail.com

Abstract

Context: The search for a safe and effective anti-diabetic medication has escalated due to the unfavorable side effects of synthetic drugs and the geometric rise in diabetes mellitus cases. Ruellia tuberosa is an important medicinal plant that can potentially reduce postprandial hyperglycemia.

Aims: To identify the inhibition of aldose reductase, dipeptidyl peptidase 4 (DPP-4), and α-glucosidase for anti-diabetic drug discovery from Ruellia tuberosa bioactive compounds using computational methods, including molecular docking, binding free energy estimates and ADMET predictions.

Methods: A molecular docking study of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin with aldose reductase, DPP-4, and α-glucosidase inhibitors was done using Glide XP-docking module. The adsorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out by the QikProp module, and ligand binding energy was ascertained by the prime molecular mechanics with generalized born and surface area (MM/GBSA) module, Schrodinger suite 2020-2.

Results: The molecular docking and complexes' MM/GBSA show specific interactions and high binding free energies. The ADMET prediction demonstrates the excellent safety profile, pharmacokinetic characteristics, and favorable drug-likeness of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin. This study shows the inhibition potential of Ruellia tuberosa compounds against aldose reductase, DPP-4, and α-glucosidase inhibitors.

Conclusions: Therefore, for this chemical to be developed further into novel pharmaceuticals for treating type 2 diabetes mellitus, optimization and experimental research are required.

Keywords: anti-diabetic; in silico ADMET; MM/GBSA; molecular docking; Ruellia tuberosa.

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Resumen

Contexto: La búsqueda de una medicación antidiabética segura y eficaz se ha intensificado debido a los efectos secundarios desfavorables de los fármacos sintéticos y al aumento geométrico de los casos de diabetes mellitus. Ruellia tuberosa es una importante planta medicinal que potencialmente puede reducir la hiperglucemia postprandial.

Objetivos: Identificar la inhibición de la aldosarreductasa, la dipeptidil peptidasa 4 (DPP-4) y la α-glucosidasa para el descubrimiento de fármacos antidiabéticos a partir de compuestos bioactivos de Ruellia tuberosa mediante métodos computacionales, incluyendo acoplamiento molecular, estimaciones de energía libre de enlace y predicciones ADMET.

Métodos: Se realizó un estudio de acoplamiento molecular de betulina, ácido betulínico, cirsiliol, cirsimarina, cirsimaritina y pedalitina con inhibidores de aldosa reductasa, DPP-4 y α-glucosidasa utilizando el módulo de acoplamiento Glide XP. La predicción de adsorción, distribución, metabolismo, excreción y toxicidad (ADMET) se llevó a cabo mediante el módulo QikProp, y la energía de unión del ligando se determinó mediante el módulo de mecánica molecular primaria con área superficial y de nacimiento generalizada (MM/GBSA), Schrodinger suite 2020-2.

Resultados: El acoplamiento molecular y el MM/GBSA de los complejos muestran interacciones específicas y elevadas energías libres de enlace. La predicción ADMET demuestra el excelente perfil de seguridad, las características farmacocinéticas y el parecido favorable a fármacos de la betulina, el ácido betulínico, el cirsiliol, la cirsimarina, la cirsimaritina y la pedalitina. Este estudio muestra el potencial de inhibición de los compuestos de Ruellia tuberosa frente a los inhibidores de aldosa reductasa, DPP-4 y α-glucosidasa.

Conclusiones: Por lo tanto, para que esta sustancia química pueda seguir desarrollándose en nuevos fármacos para el tratamiento de la diabetes mellitus tipo 2, se requiere optimización e investigación experimental.

Palabras Clave: acoplamiento molecular; antidiabético; in silico ADMET; MM/GBSA; Ruellia tuberosa.

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Citation Format: Retnaningtyas E, Setiawan A, Susatia B, Hariyanto T, Sudiwati NLPE (2024) In silico studies of Ruellia tuberosa L. compounds as aldose reductase, dipeptidyl peptidase 4, and α-glucosidase inhibitors against type 2 diabetes mellitus. J Pharm Pharmacogn Res 12(4): 735–747. https://doi.org/10.56499/jppres23.1891_12.4.735
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