Neuroprotective Effects of Tinospora Cordifolia Against Rotenone-Induced Parkinsonism: Behavioural, Biochemical and Neurochemical Evidence

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra, oxidative stress, mitochondrial dysfunction, and neuroinflammation. The rotenone-induced model reproduces key motor and neurochemical features of Parkinsonism and provides a useful experimental approach for investigating potential neuroprotective agents. Objectives: To evaluate the neuroprotective potential of a standardised hydroalcoholic extract of Tinospora cordifolia against rotenone-induced Parkinsonism in Wistar rats. Methods: Adult male Wistar rats were divided into four groups (n = 6 per group): normal control, rotenone control, standard drug-treated, and T. cordifolia-treated groups. Rotenone (2 mg/kg, subcutaneously) was administered daily for 35 days. The standard treatment consisted of levodopa (100 mg/kg) and carbidopa (10 mg/kg), while the test group received T. cordifolia extract (400 mg/kg, orally). Behavioural assessments included the rotarod test, pole test, open-field test, catalepsy test, and grip-strength test. Biochemical and neurochemical parameters included superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), nitrite, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Histopathological examination and tyrosine hydroxylase (TH) immunohistochemistry were also performed. Results: Compared with the rotenone control group, T. cordifolia-treated rats showed improvements in motor performance, including increased rotarod latency, locomotor activity, and grip strength, along with reductions in pole-test descent time and catalepsy duration. The extract-treated group also exhibited higher antioxidant enzyme activity and GSH levels, increased dopamine and its metabolite concentrations, and lower MDA, nitrite, and pro-inflammatory cytokine levels. Histopathological observations indicated comparatively better preservation of neuronal morphology, while TH-positive neuron counts were higher in the extract-treated group than in the rotenone control group. Conclusions: The hydroalcoholic extract of Tinospora cordifolia at 400 mg/kg was associated with improvements in behavioural, biochemical, neurochemical, inflammatory, and histological parameters in rotenone-induced Parkinsonism in rats. These findings suggest potential neuroprotective activity involving antioxidant and anti-inflammatory effects and partial preservation of dopaminergic neuronal characteristics. Further studies are required to establish the underlying mechanisms, dose-dependent effects, and reproducibility of these findings.