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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

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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.

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Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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Acknowledgements

We are grateful to Emanuel Mutekanga, Victor Mukundane, and Bright Rujumba, for their valuable technical assistance. The authors declare no conflict of interest. I would also like to acknowledge the DAAD fellowship for funding the PMA staff exchange that established a collaboration between Mbarara University of science and technology and Ebonyi State University

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Medicine, Mbarara University of Science and Technology, P. O. Box 1410, Mbarara, Uganda

    Deusdedit Tusubira, Jonasi Munezero, Nathiim Namale & Patrick Maduabuchi Aja

  2. Department of Biochemistry, Faculty of Science, Ebonyi State University, PMB 053, Abakaliki, Nigeria

    Peter Chinedu Agu & Patrick Maduabuchi Aja

  3. Pharm-Biotechnology and Traditional Medicine Center, Mbarara, Uganda

    Clement Olusoji Ajayi

  4. Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda

    Joseph Oloro

  5. Medical Laboratory Science, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda

    Frank Ssedyabane

  6. Department of Chemistry, Faculty of Science, Mbarara University of Science and Technology, Mbarara, Uganda

    Caroline Kiwanuka Nakiguli

  7. University of Jos/Jaris Computational Biology Centre, Jos, Nigeria

    Abayomi E. Adegboyega

  8. Mbarara University of Science and Technology, Biochemistry Department, Mbarara, Uganda

    Deusdedit Tusubira

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  1. Deusdedit Tusubira
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PMA, APC, DT conceived the idea. All authors were involved in designing the experiments, analyzing data, writing and reviewing the manuscript.

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Correspondence to Deusdedit Tusubira.

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Tusubira, D., Munezero, J., Agu, P.C. et al. 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. 11, 4 (2023). https://doi.org/10.1007/s40203-023-00141-9

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