Autophagy Modulating Potential of <i>Mucuna pruriens</i> in Parkinson’s Disease

Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, surpassed only by Alzheimer's disease. It is distinguished by a diverse array of motor and non-motor symptoms that impact various aspects of neurological function. In recent years, the autophagy-enhancing potential of several medicinal plants has been tested and results in better protection against neurodegeneration in PD. Accordingly, the major objective of this work is to explore the autophagy-enhancing activity of Mucuna pruriens (Mp) seed extract in the rotenone intoxicated mouse model. Method: To evaluate our hypothesis, we categorized the mice into four distinct groups: a control group, a drug-only control group, a rotenone-intoxicated group, and a group of rotenone-intoxicated mice that were also treated with Mp. After dosing was finished, the behavioral test was measured. The mice were then sacrificed in each group, and the brains were isolated. Rotenone-intoxicated Parkinsonian mice exhibited significant behavioral impairments in the rotarod, hanging grip, and narrow beam walking tests, indicating deficits in balance, coordination, and muscle strength. Treatment with Mp markedly improved motor performance, suggesting its neuroprotective and therapeutic potential in alleviating PD-related dysfunction. Similarly, Mp effectively mitigates biochemical impairments in the Parkinsonian mouse model, improving catalase activity, reducing nitrite levels, lipid peroxidation, and enhancing glutathione reductase function. TFEB and mTORC1 are the 2 most important modulators of autophagy. The TFEB level was decreases in the rotenone group ultimately restored in the Mp group. The activity of TFEB was negatively regulated by mTORC1. The level of mTORC1 was increased in rotenone group and was significantly reduced by Mp treatment. The enzymatic level of glucocerebrosidase was also decreased in rotenone intoxicated mice and increased in Mp group. The ultimate impact of these autophagy enhancers is reflected at the level of Tyrosine hydroxylase (TH). The activity of TH is reduced in the rotenone group and consequently enhanced by Mp treatment. Result: Our result shows the autophagy enhancing activity of Mp. Discussion: These findings support the potential of Mucuna pruriens as a neuroprotective agent through its ability to modulate key components of the autophagy pathway. By restoring TFEB expression and inhibiting mTORC1 activity, Mp may promote lysosomal biogenesis and autophagic clearance, processes essential for neuronal survival in PD. The upregulation of glucocerebrosidase and TH further confirms its role in maintaining dopaminergic neuron function. These outcomes highlight Mp’s multifaceted mechanism of action, suggesting its value not only as a symptomatic treatment but also as a disease-modifying agent. However, the study’s translational relevance requires further validation in clinical models. Conclusion: Further studies will be needed to search and test the additional number of regulators that are involved in the autophagy mediating activity of Mp.