Chanchal Garg

NO-sGC-cGMP signaling influence the anxiolytic like effect of lithium in mice in light and dark box and elevated plus maze

Glutamate is an excitatory neurotransmitter implicated in the pathogenesis of psychiatric disorders. Glutamate results in the activation of an enzyme called glycogen synthase kinase-3 (GSK-3) acting through N-methyl-d-aspartate (NMDA) receptors. Impaired expression of GSK-3 affects behavior and neurochemicals level in the brain responsible for the pathogenesis of mood disorders. It has been reported that lithium acts as an inhibitor of GSK-3 and inhibit the enzyme GSK-3 in an uncompetitive manner. In the present study, anxiolytic like effect of lithium in mice is investigated through light and dark box (LDB) and elevated plus maze (EPM). Lithium (50, 100 and 200 mg/kg, i.p.) was administered to the mice to determine the anxiety related behavior. Results obtained suggests that the administration of lithium (100 mg/kg, i.p.) reversed the anxiety related behavior of mice and decreased the levels of glutamate and nitrite as compared to control. Glutamate acting through the NMDA receptor has been found to regulate the expression of enzyme neuronal nitric oxide synthase (nNOS), which is responsible for the release of nitric oxide (NO), suggesting a possible link between NO and GSK-3 also. Therefore, to determine the possible interaction with NO, sub-effective dose of lithium was administered in combination with NO donor i.e. l-Arginine (50 mg/kg, i.p.), NOS and soluble guanylate cyclase (sGC) inhibitor i.e. methylene blue (1 mg/kg, i.p.) and phosphodiesterase inhibitor i.e. sildenafil (1 mg/kg, i.p.). The results obtained demonstrated that the anxiolytic like effect of lithium was abolished by the pretreatment with NO donor and potentiated by the pretreatment with NOS inhibitor. Therefore, it is suggested that NO signaling pathway influence the anxiolytic like activity of lithium in mice, further suggesting the link between the GSK-3 and NO signaling in the regulation of anxiety related behavior.

Anxiolytic-like effect of pyridoxine in mice by elevated plus maze and light and dark box: Evidence for the involvement of GABAergic and NO-sGC-cGMP pathway

ABSTRACT Present study was carried out to investigate the ‘anxiolytic‐like’ effect of pyridoxine in mice. Pyridoxine (90, 180 and 360 mg/kg) was administered by intraperitoneal (i.p.) route to the experimental mice and anxiety‐related behavior was evaluated by light and dark box (LDB) and elevated plus maze (EPM) models. Glutamate, GABA and nitrite levels were also determined in the isolated whole brain of mice. It was observed that pyridoxine (180 mg/kg, i.p.) exerted ‘anxiolytic‐like’ effect in mice in EPM and LDB models. Also, there was a significant increase in the levels of GABA whereas; the levels of glutamate and nitrite were decreased as compared to the control group. Administration of pentamethylene tetrazole (PTZ; 20 mg/kg, i.p.) exerted anxiogenic effects in mice, but the combination of PTZ and pyridoxine (180 mg/kg, i.p.) abolished the ‘anxiolytic‐like’ effect of pyridoxine, thereby, suggesting the possible role of GABA in the ‘anxiolytic‐like’ effect of pyridoxine in mice. Further, the influence of NO‐sGC‐cGMP pathway was investigated by administering the sub‐effective dose of pyridoxine in combination with sub‐threshold doses of NO modulators i.e. l‐arginine (50 mg/kg, i.p.; NO donor); methylene blue (1 mg/kg, i.p.; NO and soluble guanylate cyclase inhibitor) and sildenafil (1 mg/kg, i.p.; phosphodiesterase inhibitor and cGMP modulator). It was observed that the ‘anxiolytic‐like’ effect of pyridoxine in mice was counteracted by the NO donor and potentiated by the NO inhibitors. Thus, the present study confirmed the involvement of GABAergic and NO‐sGC‐cGMP pathway in the ‘anxiolytic‐like’ effect of pyridoxine in mice. HighlightsPyridoxine exerted anxiolytic like effects in mice in EPM and LDB.Pyridoxine administration increased the levels of GABA and reduced the levels of glutamate and nitrite in the brain of mice.PTZ treatment in combination with pyridoxine abolished the anxiolytic like effects of pyridoxine in mice.NO‐sGC‐cGMP pathway influenced the anxiolytic like effects of pyridoxine in mice.

IN-VITRO HYPOGLYCEMIC EVALUATION OF FRACTIONS OF HYDRO-ACOHOLIC EXTRACT OF HEARTWOOD OF TECOMELLA UNDULATA LINN.

Objective: To screen α-amylase and α-glucosidase inhibitors from the different fractions of crude hydro-alcoholic extract of heartwood of Tecomella undulata Linn. Methods: Four fractions of crude hydro-alcoholic extract of heartwood of plant were used for in-vitro inhibitory assays against digestive enzymes: α-amylase and α-glucosidase. For assay, different concentrations (20, 40, 60, 80, 100 µg/ml) were used for all fractions. Standard protocol was used for preliminary phytochemical screening of different bioactive components present in all fractions. Results: The fractions have shown moderate to highest inhibitory activity against both enzymes. But, the strong inhibition was revealed by acetone fraction against α-amylase with very minimal inhibitory concentrations at IC 50 values when compared with a standard drug acarbose. Several medicinally active phytocomponents such as flavanoids, saponin, anthraquinones, tannins, triterpenoids and phenols were observed in all studied fractions. Conclusion: The different fractions prepared from crude hydro-alcoholic extract of heartwood of plant are capable of inhibiting α-amylase and α-glucosidase and it can be concluded that heartwood of Tecomella undulata Linn. is partially active against postprandial hyperglycemia, thus diabetes mellitus. Keywords: Tecomella undulata Linn., Diabetes mellitus, α-Amylase, α-Glucosidase.