Studies on beneficial effect of hydroxytyrosol in experimental model of Parkinsons disease

Abstract

Parkinson s Disease (PD) is the second most common age related neurodegenerative disorder after Alzheimer s Disease. The present study evaluated the potential of Hydroxytyrosol (HXT) as an anti- parkinsonian molecule through in-silico, in-vitro and in-vivo approach. Through the inhibition of MAO-B, HXT decreased the dopamine turnover thereby maintained the dopamine levels in mice brain. Analysis in various transgenic mutant strains of C. elegans revealed that HXT mitigates PD pathology by preventing and#945;-synuclein accumulation and dopaminergic neuronal degeneration. In vivo study showed that HXT exerts beneficial effects on MPTP-induced motor and cognitive deficits in mice model of PD. In addition, HXT prevented the degeneration of dopaminergic neurons in MPTP- induced mice model of PD. HXT also improved MPTP-induced mitochondrial dysfunctions and reduced oxidative stress through activation of Nrf-2. HXT promoted mitochondrial biogenesis by upregulating PGC-1and#945; and other transcription factors such as Nrf-1 and TFAM. Furthermore, HXT exerted its effects on mitochondrial dynamics by enhancing mitochondrial fusion proteins. Therefore, it is conceivable from the present study that HXT has a strong neuroprotective response in PD pathology due to its antioxidant activity and ability to modulate the pathways involving dopaminergic neuronal loss. Altogether, these findings suggest HXT as a possible anti-parkinsonian molecule that may be an effective therapeutic molecule for the treatment of PD. newline