RESUMO
Self-nanoemulsifying drug delivery system (SNEDDS) containing aqueous leaf extracts of Justicia adhatoda (JA) and Psidium guajava (PG), was designed to evaluate their ability to enhance platelet count. The ternary phase diagram was constructed to identify the self-emulsifying regions and nanoemulsion prepared using clove oil, tween 80 and transcutol. The globule size of the prepared SNEDDS formulation at different folds of dilution in buffers of various pH was evaluated. The average globule size of the optimized JA2- and PG2-loaded SNEDDS at different folds of dilutions was in the range of 103.4 ± 7.1 to 238.3 ± 5.4 nm and 240.2 ± 7.9 to161.7 ± 3.7 nm, respectively. The viscosity of JA2 and PG2 loaded SNEDDS formulations were found to be 621 and 642 centipoise, respectively with no observed signs of phase separation, turbidity or precipitation during the freeze-thaw process. Oral administration of combined JA2 and PG2 loaded SNEDDS formulation to Wistar rats depleted with platelets showed a significant increase in platelet count when compared to a marketed tablet Caripill. Pharmacodynamic studies in platelet-depleted Wistar rats enhanced the platelet count after administration of SNEDDS containing lyophilized aqueous extracts JA2 and PG2.
RESUMO
OBJECTIVES: This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor-mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model. METHODS: Male Sprague-Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations. KEY FINDINGS: Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats. CONCLUSIONS: Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor-mediated glutamate/GABA abnormalities in brain.
