Effects of algerian nettle (Urtica dioica L.) on benign prostatic hyperplasia and their mechanism of action elucidation: in vivo and in silico approaches.

This study investigated the effect of Urtica dioica roots etheric extract (UDEE) on oxidative stress, and urine obstruction with histopathological examinations of prostatic and renal tissues,and suggests computational methods as a complementary method, to make a hypothesis on the overall effect of UDEE in the treatment of benign prostatic hyperplasia (BPH).Gas chromatography/mass spectrometry was utilised to characterise UDEE.BPH was induced in rats through daily subcutaneous injections of testosterone propionate. Rats were also orally administered UDEE or a vehicle. After four weeks, prostate weight, urine output, and biochemical markers were evaluated. UDEE treatment demonstrated significant regression of prostatic enlargement, improved biochemical and histopathological characteristics, and regulation of antioxidant activity levels. Phytosteroids stand out, act by inhibiting 5α-reductase and aromatase. This study provides an insight into treatment of BPH, demonstrating safety of this compound towards the kidney compared to finasteride without severe side effects.

Factorial design in the optimization and study 'in combo' of derivatives of imidazo[1,2-a]azines in the COX´s isoforms inhibition.

Background: Imidazo[1,2-a]azines with an acid group decrease inflammatory processes in murine models, and the effect has been attributed to the inhibition of COX enzymes. Results: The optimization of a series of imidazo[1,2-a]azines was performed using the reduced factorial design 23-1. The inhibitory effects of five acid derivatives of imidazo[1,2-a]azines and the standard drugs ibuprofen and indomethacin were evaluated in vitro on COX isoforms. It was observed that the different substituents provided different inhibition profiles, highlighting that the imidazo[1,2-a]pyridines are more active than the bioisosteric imidazo[1,2-a]pyrimidines. These results were analyzed using in silico docking to recognize the structural elements necessary for the inhibition of the targets. The IC50 values for COX1 and COX2 for the various compounds were as follows. COX1: 4a = 2.72 µM, 4b = 3.94 µM, 5a = 7.29µM, 5b = 63.26 µM, 6a = 12.93 µM, indomethacin = 0.13 µM, ibuprofen = 0.2 µM; COX 2: 4a = 1.89 µM, 4b = 2.39 µM, 5a = 8.08 µM, 5b = 41.15 µM, 6a = 5.86 µM, indomethacin = 0.09 µM, ibuprofen = 0.125 µM. Conclusion: Through factorial design it was possible to optimize the inhibitory response on therapeutic targets, obtaining molecule 4a as a result of factorial analysis.