Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) on 6-hydroxydopamine-(6-OHDA) induced Parkinsonism model in rats. Curcuminoids were administered (60？mg/kg, body weight, per oral) for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10？μg/2？μL) into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA), DOPAC, and HVA followed by dopamine (D2) receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry) were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D2 receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders. 1. Introduction Neurodegenerative disorders is a class of neurological diseases marked by extensive neuronal loss in the brain [1]. Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region leads to the progression of Parkinson’s disease (PD). This is followed by depletion of striatum dopamine content [2]. When up to 80% of the dopamine-producing cells are damaged, and are not able to produce enough dopamine, then the motor symptoms (bradykinesia, resting tremor, rigidity, and postural disturbances) of PD appear. 6-OHDA, a potent neurotoxin, can severely damage dopaminergic neurons in substantia nigra, leading to a significant decrease in dopamine levels, followed by precise behavioral, biochemical, and pathological changes distinctive in PD. These toxic effects can be attributed to the formation of various reactive oxygen species, lipid peroxidation, depletion of reduced glutathione, and mitochondrial complex I deficits [3]. 6-OHDA-lesioned rat model has a measurable motor deficit, which can be seen by apomorphine-induced contralateral rotations [4]. Although progress has been made in the symptomatic treatment of PD since
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