Neuroprotective role of morin hydrate on 3-nitropropionic acid-elicited huntington's disease: in vivo investigation of RIPK1/RIPK3/MLKL necroptosis signaling pathway

MH and NSA significantly mitigated body weight loss and ameliorated locomotor deterioration, besides reversing histological abnormalities in the striatum of rats. Intriguingly, MH exerted similar effects on specific biomarkers and molecular signals as NSA. MH and NSA inhibited neuroinflammation, apoptosis, and necroptosis by significantly decreasing the striatal (TNF-α), caspase 3, and necroptosis-associated proteins (P-RIPK1, P-RIPK3, and P-MLKL) levels. Besides, MH and NSA also decreased striatal GFAP and increased SDH activity. Gene enrichment analysis revealed a significant interaction between genes. Together, MH exerts a neuroprotective action on 3-NP-elicited HD rats via reducing neuroinflammation, apoptosis, and necroptosis. This study highlights MH as a potential protection against HD, calling for further research to confirm its neuroprotective effects.