Elucidating the neuroprotective potential of arbutin in 3-NPA induced HD-like pathology: Insights from in silico, in vitro, and in vivo models

Huntington’s disease (HD) is an inherited, hyperkinetic condition manifested by a triad of motor abnormalities, progressive cognitive impairment, and psychiatric disturbances. Oxidative stress has been implicated among other cellular processes in the pathogenesis of HD. Arbutin, a hydroquinone antioxidant, is reportedly neuroprotective in several animal models of neurodegenerative diseases. Hence, this research aimed to investigate the neuroprotective effect of arbutin against HD using in silico, in vitro, and in vivo experimental approaches. Schrodinger software was used for the in-silico studies, while SH-SY5Y cells were used for in-vitro studies. In the in vivo studies, adult Wistar rats were divided into five groups and 3-nitro propionic acid (3-NPA) (10 mg/kg/day,i.p) alone, and with arbutin (50 and 100 mg/kg/day,i.p.) was administered for 21 days. The body weight and behavioral parameters, including locomotor activity and motor coordination, were assessed on the 1st, 7th, 14th & 21st days. On the 22nd day, animals were sacrificed; the striatum was harvested for biochemical, neurochemical, and histopathological assessment. In silico, results indicated that arbutin showed a good binding affinity for target proteins like Akt and Nrf2. Further, arbutin prevented cell death and oxidative stress in SH-SY5Y cells induced by 3-NPA. In addition, arbutin ameliorated the 3-NPA induced motor impairments, purine nucleoside imbalances (adenosine levels and its metabolites hypoxanthine, xanthine, adenine), oxidative stress, and histological alterations in the experimental animals. In conclusion, the present findings indicate that arbutin could be used as an adjuvant for the management of Huntington’s disease.