Beneficial Effect of Xanthohumol, a Prenylated Flavanoid, on 3-Nitropropionic Acid Induced Huntington's Disease in a Rat Model

The present investigation scrutinizes the therapeutic potential of xanthohumol (XN), a potent prenylated flavonoid on 3-nitropropionic acid (3-NP) induced Huntington's disease in a murine model. 3-NP elicits prominent neurodegeneration by activation of inflammatory reactions and apoptotic mediators. Elevated oxidative stress is one of the detrimental events in 3-NP-induced neurotoxicity. In our present study, 3-NP intoxicated rats displayed significant elevation in the level of lipid peroxidation (LPO) and protein carbonyl (PC) and XN (50mg/kg) treated rats significantly diminished the LPO and PC level by attenuation of oxidative stress. Further, 3-NP insulted rats elicited significant reduction in the activities of activities of enzymic antioxidants and non-enzymic antioxidants. Whilst, treatment with XN mitigated the depleted antioxidant status by increasing the activities of enzymic and non enzymic antioxidants. Furthermore, RT-PCR analysis revealed the upregulated mRNA expression of inflammatory cytokines (TNF-alpha, IL-6) in 3-NP rats and XN intervention significantly downregulated the expression to normalcy. In addition, western blot analysis showed elevated protein expression of apoptotic markers caspase 3, Bax and decreased expression of Bcl-2 in 3-NP rats. XN administration effectively restored the altered protein expression levels to normalcy. In conclusion, our study demonstrated that xanthohumol exerts neuroprotective property against 3-NP-induced Huntington's disease mediated through antioxidant, anti-inflammatory and anti-apoptotic mechanism.