Effect of luteolin on the transgenic Drosophila model of Huntington's disease

Huntington disease (HD) is a progressive neurodegenerative disorder which deteriorates the physical and mental abilities of the patients. It is an autosomal dominant disorder and is mainly caused by the expansion of a repeating CAG triplet. The abnormal expansion of CAG trinucleotide (polyQ repeats) on the N-terminus of the Htt gene (coding the protein huntingtin, HTT) is considered to be the one of the most important factor for this disease. The mutant form of huntingtin (mHTT) not only leads to the neuronal dysfunction but also increase the oxidative stress in the neurons. In this context plant derivatives could be good therapeutic agents with minimum side effects. Luteolin (3 ',4 ',5,7-tetrahydroxyflavone) is abundantly present in many fruits and vegetables. It is a well-known anti-oxidant and has been reported to reduce oxidative stress in various models of neurodegenerative diseases. The final doses of luteolin i.e. 25, 50, 75 and 100 mu M were established in the diet and the HD flies were allowed to feed on it for 33 days. The exposure of luteolin to HD flies showed not only a dose dependent delay in the loss of climbing ability but also a dose dependent significant decrease in the oxidative stress compared to unexposed HD flies. The molecular docking studies suggest a positive interaction between mHTT and luteolin. The results suggest that the luteolin is effective in reducing the HD symptoms in transgenic Drosophila model of HD.