Tubeimoside-1 mediates significant neuroprotection in a 6-OHDA-Induced Parkinson’s disease model: unveiling a potential disease-modifying agent

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), accompanied by oxidative stress and neuroinflammation. Current treatments mainly provide symptomatic relief without altering disease progression. Tubeimoside-1 (TBMS1), a saponin compound with antioxidant and anti-inflammatory activity, has shown promise as a neuroprotective agent in experimental models. OBJECTIVE: This study aimed to assess the neuroprotective efficacy of TBMS1 in reducing motor dysfunction, oxidative stress, and neuroinflammatory responses in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). METHODS: Male Wistar rats were allocated into sham, lesion, and TBMS1-treated groups. TBMS1 (5 µM/kg) was administered intraperitoneally for four weeks. Behavioral evaluation was conducted using apomorphine-induced rotation tests. Histological and biochemical analyses measured dopaminergic integrity (Nissl and TH staining), oxidative stress markers (MDA, ROS, GSH, Nrf2), and neuroinflammation (Iba1 expression) via ELISA and immunohistochemistry. RESULTS: TBMS1 significantly reduced rotational behavior and partially restored striatal dopamine and DOPAC levels. It preserved dopaminergic neurons in the SNpc and mitigated oxidative stress by decreasing MDA and ROS while elevating GSH and Nrf2 levels. TBMS1 also reduced microglial activation, as shown by lower Iba1 expression. CONCLUSION: TBMS1 exerts notable neuroprotective effects in the 6-OHDA rat model of PD by improving motor function, limiting oxidative and inflammatory damage, and preserving dopaminergic neurons. These results suggest TBMS1 as a promising candidate for further therapeutic investigation in PD.