Molecular interaction between Serenoa repens constituents and the active site of 5alpha-reductase

What is it about?

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 - adrenoreceptor antagonists and 5-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 5-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 5- 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.

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Why is it important?

Serenoa repens is thought to inhibit prostatic 5alpha-reductase by modifying the cell membrane environment. However, this work shows that Serenoa repens constituents may directly interact with the enzyme active site, thus acting as competitive inhibitors. Even if structurally different from the endogenous substrate of the enzyme, fatty acids (particularly oleic and linoleic acid) seem to be much more involved in the enzyme inhibition than phytosterols.

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