In silico anti-diabetic study of T. diversifolia


J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 571-594, July-August 2022. DOI: Original Article In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy [ADME-T in silico y estudio de acoplamiento molecular de fitoconstituyentes de Tithonia diversifolia (Hemsl.) A. Gray en varias dianas … Continue reading In silico anti-diabetic study of T. diversifolia

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 571-594, July-August 2022.


Original Article

In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy

[ADME-T in silico y estudio de acoplamiento molecular de fitoconstituyentes de Tithonia diversifolia (Hemsl.) A. Gray en varias dianas de nefropatía diabética]

Oktavia Rahayu Adianingsih*, Uswatun Khasanah, Kevin Diagonsa Anandhy, Valentina Yurina

Department of Pharmacy, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia.



Context: Tithonia diversifolia (Hemsl.) A. Grayhas been known for treatment of diabetes mellitus, yet its mechanism as anti-diabetic has not been defined. There are various therapeutic targets for diabetes and its complication such as diabetic nephropathy.

Aims: To investigate the mechanism of phytoconstituents in Tithonia diversifolia to various targets of diabetic nephropathy and predict the pharmacokinetic profile such as absorption, distribution, metabolism, elimination, and toxicity (ADME-T).

Methods: Eighteen phytoconstituents in Tithonia diversifolia were analyzed for drug-likeness. The molecular docking of molecules was performed to protein targets, then its molecular interaction was determined. ADME-T properties were predicted using three different web servers.

Results: Drug-likeness analysis showed that all the phytoconstituents were within the range set by Lipinski’s rule of five. This study showed that Tithonia diversifolia have potential as a candidate for diabetic nephropathy therapy agent with various mechanisms by inhibiting α-glucosidase, ACE, ALR, DPP-4, LMW-PTP, RAGE, SGLT2, SUR1, and an analog of PPAR-γ. 5-Caffeoylquinic acid, catechin, diversifolin, hispidulin, tagitinin A, tagitinin C, tagitinin F, tithonine, and tirotundin were phytoconstituents with a high binding affinity to several proteins. β-gurjunene, tagitinin A,tagitinin C, tagitinin F, and tirotundin were predicted to have a better ADME-T properties than other compounds. In summary, tagitinin A, tagitinin C, tagitinin F, and tirotundin were showed the high binding affinity to various diabetes-related proteins and have a good ADME-T profile.

Conclusions: This study suggests that Tithonia diversifolia constituents have potential properties as an anti-diabetic nephropathy agent, and further studies to analyze its potency are required.

Keywords: diabetes; insulin leaf; nephropathy; Tithonia diversifolia.

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Contexto: Tithonia diversifolia (Hemsl.) A. Gray ha sido conocida para el tratamiento de la diabetes mellitus, pero su mecanismo como antidiabético no ha sido definido. Existen varios objetivos terapéuticos para la diabetes y sus complicaciones, como la nefropatía diabética.

Objetivos: Investigar el mecanismo de los fitoconstituyentes en Tithonia diversifolia para varias dianas de la nefropatía diabética y predecir el perfil farmacocinético como la absorción, distribución, metabolismo, eliminación y toxicidad (ADME-T).

Métodos: Se analizaron 18 fitoconstituyentes en Tithonia diversifolia para determinar su similitud con las drogas. Se realizó el acoplamiento molecular de moléculas a dianas proteicas, luego se determinó su interacción molecular. Las propiedades de ADME-T se predijeron utilizando tres servidores web diferentes.

Resultados: El análisis de semejanza con las drogas mostró que todos los fitoconstituyentes estaban dentro del rango establecido por la regla de cinco de Lipinski. Este estudio mostró que Tithonia diversifolia tiene potencial como candidato para el tratamiento de la nefropatía diabética con varios mecanismos mediante la inhibición de la α-glucosidasa, ACE, ALR, DPP-4, LMW-PTP, RAGE, SGLT2, SUR1 y un análogo de PPAR-γ. Ácido 5-cafeoilquínico, catequina,  diversifolina, hispidulina, tagitinina A, tagitinina C, tagitinina F, titonina y tirotundina fueron fitoconstituyentes con una alta afinidad de unión a varias proteínas. Se predijo que β-gurjunene, tagitinina A, tagitinina C, tagitinina F y tirotundina tenían mejores propiedades ADME-T que otros compuestos. En resumen, tagitinina A, tagitinina C, tagitinina F y tirotundina mostraron una alta afinidad de unión a varias proteínas relacionadas con la diabetes y tienen un buen perfil ADME-T.

Conclusiones: Este estudio sugiere que los componentes de Tithonia diversifolia tienen propiedades potenciales como agente anti-nefropatía diabética, y se requieren más estudios para analizar su potencia.

Palabras Clave: diabetes; hoja de insulina; nefropatía; Tithonia diversifolia.

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Citation Format: Adianingsih OR, Khasanah U, Anandhy KD, Yurina V (2022) In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy. J Pharm Pharmacogn Res 10(4): 571–594.

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