NOSH-aspirin (NBS-1120) attenuates motor defects and dopaminergic neuron degeneration in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a chronic, debilitating neurodegenerative disorder marked by the progressive and irreversible loss of dopaminergic (DA) neurons in the nigrostriatal pathway. Although the precise mechanisms underlying PD remain unclear, extensive research suggests that chronic neuroinflammation plays a significant role in its pathogenesis. Recently, growing evidence has pointed to NOSH-aspirin, an aspirin derivative that releases both nitric oxide (NO) and hydrogen sulfide (H(2)S), as a potent anti-inflammatory agent. However, its neuroprotective properties remain underexplored. This study assessed the protective effects of NOSH-aspirin against 6-hydroxy dopamine (6-OHDA)-induced neurotoxicity in a PD-like animal model. To induce the model, 6-OHDA (20μg/rat) was injected into the right medial forebrain bundle (MFB) of male Wistar rats (N = 7/8 per group). After 24 h, daily oral treatment with NOSH-aspirin (25 or 100 mg/kg), or aspirin (38 or 100 mg/kg), began. Included were also a sham/vehicle control group and NOSH-aspirin (100 mg/kg) starting 3 days post-6-OHDA. On the 12th day, motor function was evaluated using behavioral tests, including the rotarod treadmill, beam walking test, open field, and apomorphine-induced rotations. Animals were then sacrificed for histological and molecular analyses, including immunohistochemistry (IHC) staining and Western blotting. Results show that, NOSH-aspirin particularly at a dose of 100 mg/kg, significantly improved motor impairments and provided neuroprotection to tyrosine hydroxylase-positive (TH+) neurons. These protective effects were associated with a reduction in the phosphorylation of MAPK family proteins: JNK, p38, and ERK. In conclusion, NOSH-aspirin but not aspirin exhibits potential as a therapeutic candidate for managing neuroinflammation-related neurodegenerative disorders, including PD.