Abstract
Background:
Nitric Oxide (NO), generated by nitric oxide synthase enzymes (NOS), has an important role in maintaining synapse plasticity, neuro-modulation and other physiological functions in the brain. NO thus generated also has a key role in formation of reactive oxygen and reactive nitrite species and subsequent neuronal damage due to sustained oxidative stress. Due to its property of ROS and RNOS generation, NO plays a significant role in Parkinson's disease (PD) pathogenesis. Therefore, we evaluated the effect of mangiferin alone and in combination nNOS inhibitor 7-nitro-indazole (7-NI) in 6-OHDA lesioned rats.
Methods:
Male Wistar rats weighing 200-250 gm (n=8/group) were used in the study. Stereotactic surgeries of rats were done to induce 6-OHDA lesioning in rats. Then, treatment with mangiferin alone and in combination with 7-NI 10 mg/kg was done from day 14 to day 42 for 28 days. On day 42, rats were subjected to behavioural studies and their brains were taken out after euthanasia to perform biochemical and molecular studies.
Results:
Treatment with mangiferin and 7-NI significantly increases locomotor parameters in 6-OHDA lesioned rats. Treatment with mangiferin 45μg and 7-NI 10 mg/kg alone and in combination significantly reduces oxidative stress along with decrease in concentration of pro-inflammatory cytokines, cyclooxygenase 2 and total nitrite (NOx) and FOS B concentration.
Conclusion:
Results of this study suggest that treatment with 7-NI 10mg/kg further enhances anti-inflammatory and anti-parkinsonism activity of mangiferin owing to its property of inhibiting nNOS mediated FOS B signaling and thereby inhibiting mRNA formation of TNF-α and IL-6.
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