Elucidation of anti-prostate activities of berries of solanum aculeastrum dunal: a novel approach to management of benign prostatic hyperplasia and prostate cancer

Abstract

The prevalence of benign prostatic hyperplasia (BPH) increases with age and may progress to prostate cancer (PC). In Kenya, about 64,600 cases of BPH were recorded in 2000 which increased to 126,000 in 2019, making it worthwhile to take preventive measures of managing BPH to halt progression to PC. This study elucidated anti-prostate activities of Solanum aculeastrum Dunal berries (SADB). About 4500g of dried SADB sampled from Kakamega forest in western Kenya were extracted using methanol; from which n-hexane, dichloromethane, ethyl acetate, n-butanol, and aqueous fractions were generated and subjected to phytochemical and GC-MS profiling, except aqueous fraction. Swiss ADME and pKCSM tools were used to screen and select drug-like candidates from bioactive compounds identified with GC-MS from MESADB, HFSADB, EFSADB and DFSADB. DisGeNET and related databases were used to identify targets for bioactive compounds of extracts, BPH and PC. Molecular roles, biological processes, cellular components, and crucial pathways associated with biological processes of gene enrichment were obtained using GO & KEGG pathway analysis, respectively. Molecular docking was achieved with VINA tool. Antiproliferative and gene expression profiling were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) bioassay, and RT-qPCR respectively, and data analyzed using Graph Pad Prism (version 8.4) at p < 0.05. Glycosides, alkaloids, tannins, flavonoids, terpenoids, phenols, and saponins were identified. GC-MS profiling identified 32 compounds in methanol extracts, 25, 22, 20, and 11 compounds in the hexane, ethyl acetate, dichloromethane, and n-butanol fractions, respectively. Drug-likeness compounds of MESADB included Undecane, D-Arabinitol, and 9-Oxabicyclo [3.3.1] nonan-2-one,6-hydroxy-, with D-Arabinitol; and 9-Oxabicyclo [3.3.1] nonan-2-one,6-hydroxy-] demonstrating high binding affinity with PTGS2 and EGFR genes, significantly (p < 0.0001) inhibited growth of DU-145 cells with IC50 value and selectivity index of 5.11μg/ml and 14.84, respectively, while sparing Vero CCL-81 cells, significantly (P < 0.0001) downregulated PTGS2, EGFR and BCL-2, in treated DU-145 cells. Drug-likeness compounds of HFSADB included [(-)-cis-.beta.-Elemene; beta-Humulene; and Cadina-1(10),4-diene], with, [(-)-cis-.beta.-Elemene; and Cadina-1(10),4-diene] demonstrating strong binding affinity with PTGS2 and CYP19A1 genes, which was corroborated by in vitro studies as HFSADB significantly (p < 0.0001) inhibited growth of DU-145 cells with IC50 value and selectivity index of 5.478μg/ml and 10.67, respectively, while sparing Vero CCL-81 cells, significantly (P < 0.0001) down regulated PTGS2 and BCL-2 in treated DU-145 cells. Drug-likeness compounds of EFSADB were Thunbergol and Cycloheptane, 4-methylene-1-methyl-2-(2-methyl-1-propen-1-yl)-1-vinyl-, which showcased strong binding affinity with PIK3CA and MARK 8 genes, significantly (p < 0.0001) inhibited growth of DU-145 cells with IC50 value and selectivity index of 5.478μg/ml and 11.29, respectively, while sparing Vero CCL-81 cells, with significant (P < 0.0001) down regulation of MAPK-8 and BCL-2 in treated DU-145 cells. Drug-likeness compounds of DFSADB included Ingol 12-acetate and 1-Ethylsulfanylmethyl-2,8,9-trioxa-5-aza-1-sila-bicyclo [3.3.3] undecane with predicted activities against targets, and significantly (p < 0.0001) inhibited growth of DU-145 cells with IC50 value and selectivity index of 5.210μg/ml and 13.16, respectively, while sparing Vero CCL-81 cells, with significant (P < 0.0001) down regulation of MAPK-8, EGFR, PTGS2n and BCL-2 in treated DU-145 cells. This study strongly demonstrates anti-prostate potentials of SADB and would benefit BPH and PC patients, curb occurrence of the conditions and improve public health.