Rana M. MerghanySalma A. El‑SawiAsmaa F. Aboul NaserMohamed A. SalemShahira M. EzzatSherifa F. A. MoustafaMeselhy R. Meselhy2025-02-122025-02-122025-02-08Merghany, R. M., El-Sawi, S. A., Naser, A. F. A., Salem, M. A., Ezzat, S. M., Moustafa, S. F. A., & Meselhy, M. R. (2025). Pelargonium graveolens Attenuates Rotenone-Induced Parkinson’s Disease in a Rat Model: Role of MAO-B Inhibition and In Silico Study. Molecular Neurobiology. https://doi.org/10.1007/s12035-025-04727-6https://doi.org/10.1007/s12035-025-04727-6https://repository.msa.edu.eg/handle/123456789/6317Q1Parkinson’s disease (PD), the second most common neurodegenerative condition, is primarily characterized by motor dysfunctions due to dopaminergic neuronal loss in the Substantia Nigra (SN), with oxidative stress playing a signifcant role in its progression. This study investigates the neuroprotective potential of Pelargonium graveolens (Thunb.) L’Hér leaves in a rotenone-induced PD rat model. The total ethanolic extract and its fractions, obtained via Diaion HP-20 column chromatography, were evaluated for monoamine oxidase-B (MAO-B) inhibition in vitro. The 50% methanol fraction (PG50) demonstrated the highest MAO-B inhibition (IC50 5.26±0.12 µg/ml) compared to the reference drug selegiline (IC50 0.021±0.003 µg/ml). In a rotenone-induced PD rat model, PG50 (100 mg/kg, p.o.) alleviated motor defcits (assessed via the wire hanging test), and restored norepinephrine, dopamine, and serotonin levels. PG50 and l-dopa reduced α-synuclein levels by 367.60% and 377.48%, respectively. Oxidative balance was restored with increased glutathione (23.12%) and decreased malondialdehyde (164.19%) in brain tissues. PG50 signifcantly reduced serum TNF-α (572.79%) and IL-6 (70.84%) levels, and improved succinate dehydrogenase (14.47%) and lactate dehydrogenase (7.74%) activities in brain tissues. Histopathological alterations in the SN were also ceased. UPLC-MS/MS analysis identifed 61 metabolites, including 32 favonoids, 13 phenolic acids, 7 coumarins, 5 phenolic glycosides, and 4 dicarboxylic acids, with in silico docking showing strong MAO-B binding by methoxylated favonoids like methoxyluteolin dimethyl ether (docking score:−8.0625 kcal/mol), surpassing that of safnamide (−8.2615 kcal/mol). These fndings suggest that P. graveolens holds promise as a neuroprotective agent against rotenone-induced PD.en-USParkinson’s disease · α-Synuclein · Neuro-infammation · Oxidative stress · MAO-B · Pelargonium graveolensArticlehttps://doi.org/10.1007/s12035-025-04727-6