Medicinal Implications of <em>Phyllanthus</em> Species: Neuroprotection Against Rotenone-Induced Cytotoxicity in SH-SY5Y Cells

Although Phyllanthus species possess a rich history of ethnomedicinal use, their potential in managing neurodegenerative disorders remains under-explored. This study screened ten Phyllanthus species for antioxidant profiles and monoamine oxidase (MAO) inhibition to identify candidates for neuroprotection. Among the tested species, P. emblica emerged as the most potent candidate, exhibiting superior radical scavenging activity, reducing power, and dual MAO-A/B inhibition. These bioactivities were strongly correlated with its high content of phytoconstituents, including total phenolics, flavonoids, and phenylpropanoids. Notably, P. urinaria displayed distinctive selectivity as an MAO-B inhibitor. In a rotenone-induced Parkinson’s disease (PD) model using SH-SY5Y cells, both species significantly mitigated neurotoxicity by attenuating oxidative stress. Mechanistically, treatments with both Phyllanthus species reduced intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation while preserving glutathione (GSH) levels and restoring superoxide dismutase (SOD) and catalase activities. Collectively, these findings demonstrate that P. emblica and P. urinaria confer neuroprotection through a multi-target mechanism involving direct antioxidant action, enhancement of endogenous defenses, and enzyme modulation, highlighting their potential as therapeutic agents.