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Oxidative stress is known to play a vital role in the progression of neurodegenerative diseases. The current treatment method primarily targets symptoms by using anti-Parkinson drugs such as levodopa, carbidopa, dopamine (DA) agonists, monoamine oxidase type B inhibitors, and anticholinergics to replace DA. However, these drugs pose severe side effects when used for a prolonged time. Hence, there is a need for a concerted effort to develop natural compounds that reduce oxidative stress and help in the management of PD symptoms. This study aimed to investigate the neuroprotective effects of the petroleum ether extract of Achillea millefolium and its fractions on SH-SY5Y and SK-N-SH neuroblastoma cells using Bioactivity-guided fractionation. To isolate the bioactive fraction, the crude extract was separated on gravity column chromatography. Of the twenty-one fractions collected, one of the fractions (Fraction 4) was found to be the most potent neuroprotective to neuronal cells exposed to the neurotoxins, rotenone, and 6-hydroxydopamine. The results showed Fraction 4's ability to reduce apoptosis by scavenging ROS, maintaining mitochondrial membrane potential, increasing superoxide dismutase activity, and increasing Sirtuin 3 presence and activity. Fraction 4 also showed the ability to reduce cellular apoptosis through the regulation of the AKT cell signaling pathway. The major compounds present in Fraction 4 were analyzed on TOF-LC-MS. Phosphatidic acid (PA 32:0) and four diacylglycerols (DAG) compounds were identified and characterized for their neuroprotective effect.

In this review, we present evidence collected over a decade concerning signaling pathways and pathogenic mechanisms that are associated with oxidative stress in Parkinson's disease. Parkinson's is associated with several protein such as α-synuclein and signaling pathways such as Wnt signaling pathway. The review highlights the connection of the Wnt mediated pathway with other biological pathways that are known to have a role in neurodegeneration and the orchestrated role of several proteins in mitochondrial oxidative stress in Parkinsons. We have highlighted neuroprotective agents that eliminate the excess of reactive oxygen species and have a potential to be developed as therapeutics for Parkinson.

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