Further Investigations on the Neuroprotective Potential of Centella siatica against Sleep Deprivation Induced Anxiety like Behaviour: Possible Implications of Mitoprotective and Anti-Stress Pathways
Introduction: Sleep deprivation [SD] often raises several neurological problems by causing significant alterations at multiple neural systems. Centella asiatica is a psychoactive medicinal herb with immense therapeutic potential.
Objective: The present study has been designed with aim to target mitoprotective and anti-stress pathways involved in the protective effect of Centella asiatica in addition to nitric oxide mechanism.
Methods: Male laca mice were sleep deprived for 72 hours using grid suspended over water method and Centella asiatica (150 and 300mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72 hours sleep deprivation. Various behavioural (pentobarbitone induced sleep time i.e. sleep latency as well as total sleep time and assessment of anxiety like behaviour), mitochondrial enzyme complex activities, serum corticosterone levels as well as pyknotic cell density in thalamo-cortical region were assessed subsequently.
Results: Centella asiatica (150 and 300mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect, reversed mitochondrial enzyme complex activities, attenuated corticosterone level as well as improved neuroinflammatory and apoptotic responses (pyknotic cell density) as compared to 72 hours sleep deprived animals. Upon treatment with Centella asiatica, the parameters of pentobarbitone induced hypnosis though modified but were not found to be significant in comparison to the sleep deprived animals. Further, L-arginine (100 mg/kg) pre-treatment significantly reversed protective effect of Centella asiatica (150 mg/ kg) in 72 hour sleep deprived animals. However, L-NAME (10 mg/ kg) pretreatment with Centella asiatica (150 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se.
Conclusion: The present study suggests mitoprotective; antistress pathways are also involved in the protective effect of Centella asiatica via nitric oxide modulatory mechanisms against sleep deprivation induced anxiety-like behaviour in mice.