In silico and in vitro evaluation of compounds from Methanol whole extracts of Solanum aculeastrum Dunal berries against benign prostatic hyperplasia and prostate cancer

Gift Crucifix Pender 1, 2, *, Bernard Guyah 1, Peter G Mwitari 3, Mercy Jepkorir 3, Inyani John L. Lagu 4 and James Ombaka 

1 Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Kenya.
2 Department of Pharmacology and Toxicology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
3 Center for Traditional Medicine and Drug Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
4 Pan African University for Basic Sciences, Technology, and Innovation (PAUSTI), Nairobi, Kenya.
5 Department of Pharmaceutical Sciences, School of Public Health and Community Development, Maseno University, Kenya.
 
Research Article
International Journal of Science and Research Archive, 2024, 13(01), 193–217.
Article DOI: 10.30574/ijsra.2024.13.1.1616
Publication history: 
Received on 20 July 2024; revised on 01 September 2024; accepted on 03 September 2024
 
Abstract: 
Background: This study evaluated anti-prostate potentials of compounds from methanol extract of Solanum aculeastrum Dunal berries (MESADB) against benign prostatic hyperplasia (BPH) and prostate cancer (PC).
Methods: We used Swiss ADME and pKCSM tools to select drug-like candidates from MESADB. DisGeNET and related databases were used to identify targets for compounds of MESADB, BPH and PC. Molecular roles, biological processes, cellular components involved, and crucial pathways associated with biological processes of gene enrichment were obtained using Gene Ontology (GO) & Kyoto Encyclopedia of Genes and Genomes (KEGG), respectively. Docking was achieved using VINA tool. Antiproliferative and gene expression profiling were determined using 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).
Results: Three ideal drug-like candidates [Undecane; D-Arabinitol; and 9-Oxabicyclo [3.3.1] nonan-2-one,6-hydroxy-] were identified. Key targets included TLR4, PTGS2, STAT3, ESR1, MTOR, SRC, MMP9, HDAC1, AKT1 and EGFR. GO analysis revealed key targets were mainly enriched in 601 biological processes (BP), 53 molecular function (MF) and 24 cellular components (CC) terms (p < 0.05). KEGG analysis presented pathways for cancer, pathway of proteoglycans in cancer, amongst others. Docking revealed [D-Arabinitol; and 9-Oxabicyclo [3.3.1] nonan-2-one,6-hydroxy-] demonstrated high binding affinity with PTGS2 and EGFR. MESADB 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. There were significant (p < 0.0001) downregulations of EGFR, PTGS2 and BCL-2, in treated DU-145 cells compared to control.
Conclusion: MESADB possesses antiprostate potentials.
 
Keywords: 
In silico; In vitro; Methanol-extract-of-Solanum-aculeastrum-Dunal-berries; Benign prostatic hyperplasia; Prostate cancer
 
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