Hypothesis on Serenoa repens (Bartram) small extract inhibition of prostatic 5α-reductase through an in silico approach on 5β-reductase x-ray structure
- Published
- Accepted
- Subject Areas
- Computational Biology, Pharmacology
- Keywords
- Serenoa repens (Bartram) Small, Benign prostatic hyperplasia, 5α-reductase, Molecular docking, PyRosetta, AutoDock
- Copyright
- © 2016 Governa et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2016. Hypothesis on Serenoa repens (Bartram) small extract inhibition of prostatic 5α-reductase through an in silico approach on 5β-reductase x-ray structure. PeerJ Preprints 4:e2543v1 https://doi.org/10.7287/peerj.preprints.2543v1
Abstract
Benign prostatic hyperplasia is a common disease in men aged over 50 years old, with an incidence increasing to more than 80% over the age of 70, that is increasingly going to attract pharmaceutical interest. Within conventional therapies, such as α-adrenoreceptor antagonists and 5α-reductase inhibitor, there is a large requirement for treatments with less adverse events on, e.g., blood pressure and sexual function: phytotherapy may be the right way to fill this need. Serenoa repens standardized extract has been widely studied and its ability to reduce lower urinary tract symptoms related to benign prostatic hyperplasia is comprehensively described in literature. An innovative investigation on the mechanism of inhibition of 5α-reductase by Serenoa repens extract active principles is proposed in this work through computational methods, performing molecular docking simulations on the crystal structure of human liver 5β-reductase. The results confirm that both sterols and fatty acids can play a role in the inhibition of the enzyme, thus, suggesting a competitive mechanism of inhibition. This work proposes a further confirmation for the rational use of herbal products in the management of benign prostatic hyperplasia, and suggests computational methods as an innovative, low cost, and non-invasive process for the study of phytocomplex activity toward proteic targets.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
Autodock binding energy evaluation of 5AR homology model in complex with different substrates (kcal/mol)
PyRosetta computed absolute energies and computed binding energies (kcal/mol)
DUD-E generated decoys binding energies (kcal/mol) obtained by PyRosetta, using 5BR as a target protein
Stigmasterol (a,b), campesterol (c,d) and daucosterol (e,f) in the unproductive (left) and productive (right) position
Lauric acid (a,b), miristic acid (c,d), palmitic acid (e,f) and linoleic acid (h,i) in the unproductive (left) and productive (right) position
5AR type 1 and 5BR sequence alignment
Binding site residues are sharpened in light green; active site residues are sharpened in olive green.
5AR type 2 and 5BR sequence alignment
Binding site residues are sharpened in light green; active site residues are sharpened in olive green.