The effect of 1-cyclopentyl-3-ethyl-6-(3-ethoxypyrid-4-yl)-1H-pyrazolo [3,4-d]pyrimidin-4-one (SR 265579), a potent inhibitor of guanosine 3',5'-cyclic monophosphate (cyclic GMP) phosphodiesterase (PDE5), was examined regarding its specificity toward the other cyclic nucleotide phosphodiesterases, the effect on cyclic nucleotide levels and the bronchodilatory activity, both in vitro and in vivo in guinea-pigs. The effects were compared to those obtained with zaprinast (CAS 37762-06-4), a known PDE5 inhibitor. Anion-exchange chromatography of the soluble fraction of guinea-pig homogenates revealed 5 peaks which corresponded to PDE1, PDE2, PDE3, PDE4 and PDE5. SR 265579 produced a potent and competitive inhibition, with respect to cyclic GMP, of PDE5 with a Ki of 6.4 nmol/l. The compound was 25 fold more potent than zaprinast and demonstrated selectivity toward PDE5. The selectivity index was 14 and 33 with respect to PDE4 and 3, respectively. PDE1 and 2 were only inhibited at considerably higher concentrations. SR 265579 specifically increased the intracellular cyclic GMP levels in guinea-pig tracheal epithelial cells (EC 50 = 117 nmol/l). Moreover, in the guinea pig, plasma cyclic GMP levels were significantly increased after the intravenous or oral administration of doses as low as 1 mg/kg. Isolated guinea-pig trachea were relaxed by the addition of SR 265579 as evaluated by measuring either spontaneous tone or relaxation of histamine and acetylcholine-precontracted preparations. PD 2 values were of 7.64, 6.52 and 5.25, respectively. In vivo, after i.v. administration, bronchodilatory activity was demonstrated in an artificially-ventilated guinea-pig histamine-induced bronchospasm model with an ED 50 of 0.63 mg/ kg. In all experiments, SR-265579 was proved to be more active than zaprinast. These results demonstrate that SR 265579 is an orally active, potent and specific inhibitor of PDE5.

This study was aimed at evaluating the curative effects of Hydroethanolic Extract Of Spirulina platensis (HESP) on the reproductive function of female Guinea pig exposed to oxidative stress. Sixty females, 3-4 months old, weighing 300-400 g were divided into six groups (10 animals/group). The neutral control received distilled water, the negative control was treated with lead acetate at a dose 12 mg/kg.b.w while the positive control was given 12 mg of lead acetate/kg b.w and 100 mg of vitamin C. Groups 4, 5 and 6 were treated with lead acetate at a dose of 12 mg/kg b.w for the first 30 days and then received from the 31 st day to the 90 th day HESP at doses of 50,100 and 200 mg/kg.b.w respectively once daily. Results revealed that lead caused prominent toxic effects on fertility, deterioration of sex organs as well as a disruption of serum levels of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and progesterone. Lead acetate markedly increased tissues oxidative-stress marker (malondiadehyde), whereas it reduces the activities of antioxidant-enzymes, Superoxide Dismutase (SOD), total peroxidase and catalase. These changes were also accompanied by a significant (p<0.05) decrease of body weight gain. However treatment with HESP ameliorated lead acetate-induced anomalies by significantly (p<0.05) increasing the body weight gain, organ weights and feed intake. Also HESP let to a significant (p<0.05) improvement of fertility indices, a significant (p<0.05) increase in serum LH, FSH, progesterone hormones and an increase in antioxidant enzymes. Curative treatment brought about histological tissues protection and a significant (p<0.05) decrease of toxicity biomarkers (AST, ALT, creatinine and urea) and Malondiadehyde (MDA). In conclusion, lead acetate induced reproductive stress and administration of HESP can mitigate these adverse effects due to its antioxidant properties.

The present study was undertaken to evaluate the effects of Hutch leaves Ethanolic Extract (EE) on reproductive parameters, toxicity biochemical markers and oxidative stress indicators in does exposed to Potassium Dichromate (PD). Thirty-six nulliparous sexually mature does of eight months; weighing 2.80-3.00 kg were divided into six groups of six animals, comparable in terms of Body Weight (BW). After mating, group T0 received distilled water, while groups T0-, VC100, EE100, EE200 and EE400 were treated with 40 mg/BW of PD. Also, group VC100 received 100 mg/BW of vitamin C, while groups EE100, EE200 and EE400 received respectively 100, 200 and 400 mg/BW of EE of hutch leaves. Results showed that urea, creatinine, total cholesterol, alanine aminotransferase and aspartate aminotransferase were significantly higher; with lower total protein levels in T0-concerning the other groups. The follicle-stimulating hormone was significantly lower in T0-as compared to the other groups. Catalase and total peroxidase activities decreased significantly while malondialdehyde and superoxide dismutase increased significantly in T0-than in other groups. From these results, EE of Hutch leaves has protected does against the toxic effects of PD. It can therefore be used to improve female reproduction.

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Aims: Ocimum gratissimum is an aromatic and medicinal plant, well known for its medicinal values such as antifungal properties. This study aimed at evaluating the effect of T. diversifolia powder and compost use as biofertilizer on the growth parameters, essential oil (EO), total phenolic and flavonoid content and anticandida activity of O. gratissimum. Study Design: O. gratissimum plants were cultivated for 8 months in an experimental farm designed as a split plot into 4 blocks. Each block was amended (main factor) either with T. diversifolia compost (150 g/plant), powder (40 g/plant) or the synthetic fertilizer NPK (10 g/plant), respectively, followed by sprayed (second factor) with same fertilizer at 20 g/L, 20 g/L and 2 g/L or water every two weeks after transplantation. The control block received no amendment and was sprayed with water or the previous fertilizer. Place and Duration of Study: This work was carried out within August 2019 to October 2020 in Yaoundé-Cameroon. Methodology: Plant growth parameters (fresh and dry leaves weight, florescent weight and plant height) were evaluated at four and eight months after transplantation. The harvested fresh leaves were hydrodistillated for EO and the hot aqueous extract. Both extracts were used for the evaluation of the anticandida activity while the latter was submitted to total flavonoids and phenolic analyses. Results: At 4 and 8 months after transplantation, the synthetic fertilizer and T. diversifolia compost significantly increased plant growth parameters as compared to other treatments. The plants treated with T. diversifolia biofertilizer compost showed the highest total phenolic (53.16 µg GAE/µL), flavonoid (36.32 µg// GAE/µL) content, and EO yield (0.666%). The EO from O. gratissimum treated with T. diversifolia compost showed the best inhibitory activity on C. albicans NR-29451. Conclusion: This study showed that T. diversifolia compost was a promising organic fertilizer in optimizing the growth, secondary metabolites and anticandida activity of O. gratissimum.