Aescin Protects against Experimental Benign Prostatic Hyperplasia and Preserves Prostate Histomorphology in Rats via Suppression of Inflammatory Cytokines and COX-2.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urogenital condition in aging males, while inflammation and tissue proliferation constitute the main pathophysiological factors. The adverse effects of currently available BPH medications limit patient compliance. We tested the protective effect of aescin against the development of BPH in rats. METHODS: A total of 18 male Wistar rats were divided into 3 groups: control (sesame oil 1 mL/kg, s.c.); BPH (testosterone oenanthate 3 mg/kg, s.c., in sesame oil), and BPH-aescin rats (testosterone oenanthate 3 mg/kg, s.c. + aescin 10 mg/kg/day, p.o.). All treatments continued for 4 weeks. Serum and prostatic samples were harvested for biochemical and histopathological examination. RESULTS: Induction of BPH by testosterone increased the prostate weight and prostate weight index, serum testosterone, prostate expression of inflammatory (IL-1ß, TNF-α, and COX-2), and proliferative markers (PCNA and TGF-ß1). Concurrent treatment with aescin decreased the testosterone-induced increase in prostatic IL-1ß, TNF-α, and COX-2 expression by 47.9%, 71.2%, and 64.4%, respectively. Moreover, aescin reduced the prostatic proliferation markers TGF-ß1 and PCNA by 58.3% and 71.9%, respectively, and normalized the prostate weight. CONCLUSION: The results of this study showed, for the first time, that aescin protected against the development of experimental BPH in rats via its anti-inflammatory and antiproliferative effects. These findings warrant further studies to clinically repurpose aescin in the management of BPH.

Synthesis and vasodilator activity of some pyridazin-3(2H)-one based compounds.

Aim: Hypertension is a major health problem worldwide resulting in high death rates due to its consequences and complications. Therefore, searching for new vasorelaxants is a must to find new vasodilators efficient for the treatment of different cardiovascular diseases. Methodology: Different 6-phenyl-3-pyridazinone based derivatives were synthesized and screened for their vasorelaxant activity according to the reported method using hydralazine as a standard. Results: The tested compounds revealed potent to mild activity with EC50 values 0.339-114.300 µM compared with hydralazine EC50 = 18.210 µM. Conclusion: The most active compounds were the acid 5, its ester analog 4 and 4-methoxyphenylhydrazide derivative 10c (EC50 = 0.339, 1.225 and 1.204 µM, respectively). Therefore, 6-phenylpyridazin-3(2H)-one can be a hit for structural optimization to obtain promising vasorelaxants.

Design and synthesis of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as PDE 4B inhibitors endowed with bronchodilator activity.

A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives was designed, synthesized, and screened for their phosphodiesterase (PDE 4B) inhibitory activity and bronchodilation ability. Compound 7e showed 41.80% PDE 4B inhibition at 10 µM. Eight compounds were screened for their bronchodilator activity, where compounds 7f and 7e elicited promising bronchodilator activity with EC50 values of 18.6 and 57.1 µM, respectively, compared to theophylline (EC50 = 425 µM). Molecular docking at the PDE 4B active site revealed a binding mode and docking scores comparable to those of a reference ligand, consistent with their PDE 4B inhibition activity.