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.

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 5mg/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, butanone, 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