RUTIN FROM RUTA CHALEPENSIS ALLEVIATES ROTENONE-INDUCED DOPAMINE DEPLETION AND MOTOR DEFICITS THROUGH ANTI-OXIDATIVE AND ANTI-APOPTOTIC EFFECTS IN A RAT MODEL OF PARKINSON’S DISEASE

Objectives: Rutin, a flavonol glycoside derived from Ruta chalepensis, has shown antioxidant and anti-apoptotic properties in in vitro models of
Parkinson’s disease (PD); however, its neuroprotective mechanisms in vivo remain inadequately characterised. The present study aimed to evaluate
the neuroprotective and anti-apoptotic effects of rutin in a rotenone-induced rat model of PD.
Methods: Male albino Wistar rats were administered rotenone (2.5 mg/kg, intraperitoneally) for 28 days to induce Parkinsonian features. Rutin
was administered orally at doses of 5, 10, and 20 mg/kg to determine the optimal neuroprotective concentration. Motor performance was assessed
using behavioral tests, followed by estimation of striatal dopamine levels, oxidative stress markers, antioxidant enzyme activities, and expression of
dopaminergic and apoptotic proteins.
Results: Rotenone administration resulted in significant motor impairment, striatal dopamine depletion, increased oxidative stress, reduced
expression of tyrosine hydroxylase, dopamine transporter, and vesicular monoamine transporter-2, elevated α-synuclein levels, and activation of
apoptotic signaling characterised by increased Bax, cytochrome c, and caspases-3, -8, and -9, along with decreased Bcl-2 expression. Rutin treatment
produced a dose-dependent improvement in motor function, with 10 mg/kg identified as the most effective dose. Co-treatment with rutin (10 mg/kg)
significantly restored antioxidant enzyme activities, normalized dopaminergic protein expression, reduced α-synuclein accumulation, and suppressed
apoptotic pathways.
Conclusion: These findings demonstrate that rutin confers significant neuroprotection against rotenone-induced dopaminergic neurodegeneration
by attenuating oxidative stress and apoptosis in vivo. Rutin may represent a promising candidate for disease-modifying therapy in PD, warranting
further investigation of its mitochondrial and anti-inflammatory mechanisms.