In a rotenone mouse model of Parkinsonism, oral luteolin (100–200 mg/kg) reduced oxidative stress and neuroinflammation, improved motor behavior and neuronal histology, and modulated TNF-α, FMRP, serotonin, and tyrosine hydroxylase expression.

The study supports luteolin as a neuroprotective candidate acting on mitochondria-linked toxin pathology and inflammatory pathways—relevant to PD biology and repurposing—but translational potential is limited by high doses, no PK/α‑synuclein or target-validation data, and reliance on a single toxin…

Exposure of pesticide and complex I inhibitor, rotenone has been shown to reproduce features of Parkinson's disease, including selective nigrostriatal dopaminergic degeneration and α-synuclein-positive cytoplasmic inclusions. Sixty mice were randomly divided into six groups (n=10) and orally treated for 28 consecutive days as follows; group 1: vehicle (10 mL/kg), group 2- vehicle + rotenone (10 mg/kg p.o. in 0.5% carboxymethyl cellulose (CMC), group 3 - rotenone + 100 mg/kg Luteolin, group 4 - rotenone + 200 mg/kg Luteolin, group 5 - 100 mg/kg Luteolin and group 6 - 200 mg/kg Luteolin, respectively. At the end of the experiment, brain tissues were harvested for biomarkers of oxidative stress, neurobehavioural studies, histology, and immunohistochemistry of Tumour Necrosis Factor alpha (TNF-α), Fragile X Mental Retardation Protein (FXMRP), serotonin, and tyrosine hydroxylase were evaluated. Rotenone toxicity significantly enhanced biomarkers of oxidative stress, acetylcholinesterase activity, and declined antioxidant defense system. Significant reduction in motor coordination and movement disorder together with vacuolation (demyelination) and atrophy of neurons were observed in ROT-untreated mice. Treatment of mice with Luteolin lowered oxidative stress biomarkers, neuroinflammation, Fragile X Mental Retardation Protein expression, improved expression of serotonin and tyrosine hydroxylase production, and restored neuronal ultrastructure anarchy.