Protective Effect of Andrographolide in 3-Nitropropionic Acid Induced Huntington Disease and Associated Neurodegenerative Changes in Rats

Aims: Oxidative stress and activation of pro-apoptotic mediators have been associated with the pathogenesis of Huntington’s disease. Andrographolide (ANDRO) is a well-known antioxidant and inhibitor of pro-apoptotic mediator, nuclear factor kappa B (NF-kB).

Study Design: The present study was hence designed to evaluate the effect of ANDRO in Huntington’s disease.

Place and Duration of Study: Department of Pharmacology, Khalsa College of Pharmacy, Amritsar, India between March 2018 and July 2018.

Methodology: Five groups (n=6) of Sprague dawley rats were used. Normal group animals were kept untreated. The control group was administered 3-Nitro propionic acid (3-NP) for seven days. The three treament groups received 3-NP followed by ANDRO intraperitoneally for seven days. On 8th day, behavioral and coordination parameters were evaluated using multiple tests. Oxidative stress and anti-oxidant enzyme levels in brain tissue were also evaluated. Brain tissues were also evaluated using Haematoxylin-eosin staining.

Results: Administration of 3-NP resulted in motor incoordination and muscle weakness as indicated by behavioral tests. Biochemically, there was an increase in the oxidative stress and depletion of free radical scavenging. Histopathologically, there was severe neuronal degeneration and neural tissue apoptotic changes in the rat striatum. ANDRO administration resulted in significant decrease in the muscle incoordination in the behavioral tests and also decreased prooxidative biochemical changes. Brain tissues of the ANDRO treated animals showed protection against neuronal damage and neurodegeneration.

Conclusion: The results indicate that the use of ANDRO may afford protection against Huntington’s disease associated muscle incoordination and subsequent neurodegeneration. Present study provides a lead for further investigation of role of NF-kB inhibitors in Huntington’s disease and possible development of low-cost natural medication.