In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor

Deusdedit Tusubira; Jonasi Munezero; Peter Chinedu Agu; Clement Olusoji Ajayi; Joseph Oloro; Nathiim Namale; Frank Ssedyabane; Caroline Kiwanuka Nakiguli; Abayomi E Adegboyega; Patrick Maduabuchi Aja

doi:10.1007/s40203-023-00141-9

In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor

In Silico Pharmacol. 2023 Mar 1;11(1):4. doi: 10.1007/s40203-023-00141-9. eCollection 2023.

Authors

Affiliations

¹ Biochemistry Department, Faculty of Medicine, Mbarara University of Science and Technology, P. O. Box 1410, Mbarara, Uganda.
² Mbarara University of Science and Technology, Biochemistry Department, Mbarara, Uganda.
³ Department of Biochemistry, Faculty of Science, Ebonyi State University, PMB 053, Abakaliki, Nigeria.
⁴ Pharm-Biotechnology and Traditional Medicine Center, Mbarara, Uganda.
⁵ Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
⁶ Medical Laboratory Science, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
⁷ Department of Chemistry, Faculty of Science, Mbarara University of Science and Technology, Mbarara, Uganda.
⁸ University of Jos/Jaris Computational Biology Centre, Jos, Nigeria.

Abstract

Benign Prostatic Hyperplasia (BPH) is a major cause of lower urinary tract infections and erectile dysfunction thus a major contributor to lowering the quality of life among older men. In this study, we investigated the molecular mechanism of Colocasia esculenta (CE) as a novel agent for BPH chemotherapy. In vivo, we assigned 45 male Wistar albino rats about 6 weeks old into 9 experimental groups (n = 5). BPH was induced in groups 2-9 with 3 mg/kg of Testosterone Propionate (TP) subcutaneously. Group 2 (BPH) was not treated. Group 3 was treated with 5 mg/kg Finasteride (standard drug). Group 4-9 were treated each with 200 mg/kg body weight (b.w) of CE crude tuber extracts/fractions (ethanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous). At the end of treatment, we sampled the rats' serum to check the level of PSA. In silico, we conducted a molecular docking of the crude extract of CE phenolics (CyP) previously reported, targeting 5α-Reductase and α1-Adrenoceptor linked to the BPH progressions. We adopted the standard inhibitors/antagonists (5α-reductase: finasteride; α1-adrenoceptor: tamsulosin) of the target proteins as controls. Furthermore, the pharmacological properties of the lead molecules were studied in terms of ADMET using swissadme and pKCSM resources, respectively. Results showed that administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA levels whereas CE crude extracts/fractions significantly (p < 0.05) lowered the serum PSA level. Also, fourteen of the CyPs bind to at least one or two of the target proteins with their binding affinity of between - 9.3 to - 5.6 kcal/mol and - 6.9 to - 4.2 kcal/mol, respectively. The CyPs possess better pharmacological properties compared to the standard drugs. Therefore, they have the potentials to be enlisted for clinical trials towards the management of BPH.

Keywords: 5α-reductase; BPH; Colocasia esculenta phenolics; Lead molecules; Molecular mechanism; α1-adrenoceptor.

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.