Potential activity of Aframomum daniellii (Zingiberaceae) dry seeds: A case study of its action mechanism on the Wistar rat strain with testicular deficiency.

This work was undertaken to evaluate the biological activity of the aqueous extract of the dry seeds of Aframomum daniellii seeds on the copulatory performance of rats with testicular deficiency. Hypogonadal adult male rats (30) were divided into 6 groups: group I received distilled water (10 ml/kg), group II received sildenafil citrate (5 mg/kg), group III received intramuscular injections of testosterone enanthate (3. 6 mg/kg), group IV, V, and VI received the aqueous extract of A. daniellii at the respective doses of 100, 200, and 400 mg/kg/po/day for 14 days. The copulatory performance of the animals were assessed on days 1, 7 and 14 through the following copulation parameters: Mount, intromission, and ejaculation latency (ML, IL, and EL) and frequency (MF, IF and EF), average interval of copulation (AIC) and post-ejaculatory interval (PEI)). We noticed a significant decrease of ML (p < 0.05), IL (p < 0.01), EL (p < 0.001) and the increase of MF, IF and EF (p < 0.01) particularly at doses of 100 and 400 mg/kg when compared to group I and II. In addition, we noticed a significant increase of AIC from day 7 (p < 0.05) to day 14 (p < 0.001) at the same two doses while the PEI significantly decreased from the 1st (p < 0.01) to the 14th day (p < 0.001) when compared to group I and II. These findings demonstrated that A. daniellii aqueous extract of seeds enhanced pro-sexual potential and pro-sexual desire in male rats with testicular deficiency.

Discovery of novel Hepatitis C virus inhibitor targeting multiple allosteric sites of NS5B polymerase.

HCV is a viral infection posing a severe global threat when left untreated progress to end-stage liver disease, including cirrhosis and HCC. The NS5B polymerase of HCV is the most potent target that harbors four allosteric binding sites that could interfere with the HCV infection. We present the discovery of a novel synthetic compound that harbors the potential of NS5B polymerase inhibition. All eight compounds belonging to the benzothiazine family of heterocycles displayed no cellular cytotoxicity in HepG2 cells at nontoxic dose concentration (200 µM). Subsequently, among eight compounds of the series, merely compound 5b exhibited significant inhibition of the expression of the HCV NS5B gene as compared to DMSO control in semi-quantitative PCR. Based on our western blot result, 5b at the range of 50, 100 and 200 µM induced 20, 40, and 70% inhibition of NS5B protein respectively. To estimate the binding potential, 5b was docked at respective allosteric sites followed by molecular dynamics (MD) simulations for a period of 20 ns. In addition, binding free energy calculation by MM-GB/PBSA method revealed a conserved interaction profile of residues lining the allosteric sites in agreement with the reported NS5B co-crystallized inhibitors. The presented results provide important information about a novel compound 5b which may facilitate the the discovery of novel inhibitors that tends to target multiple sites on NS5B polymerase.