Aquilaria agallocha Mitigates MPTP Induced Parkinson's Disease by Targeting the BDNF/GDNF and NRF2 Pathways: A Network Pharmacology and an in vivo Study

Background

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder marked by the neuronal death and a complex, multifaceted etiology. The present study aimed to investigate the potential of Aquilaria agallocha (AA; Family: Thymelaceae) leaf extract on MPTP-induced Parkinson’s disease in Wistar rats, utilising in silico and in vivo protocols.

Material and Methods

Bioactive-target interactions were studied via network pharmacology and docking. Protein-ligand binding was assessed using AutoDock Vina. Parkinson’s disease was induced in male Wistar rats via intranasal MPTP. Rats were treated with extract doses (50, 100, 200 mg/kg) and levodopa. Behavioural tests (open field, rotarod, beam walk, grid hanging), neurochemical assays (TBARS, SOD, catalase, dopamine), and ELISA-based biomarker estimation (GDNF, BDNF, LRRK2, NRF2) were conducted.

Results

Network pharmacology revealed 45 Parkinson's-related targets and key pathways, including apoptosis, PI3K-Akt, and neurotrophin signalling. Molecular docking showed strong binding of 12-deoxyphorbol and Clemiscosin D with MAPK3/MAPK1, BDNF/GDNF, LRRK2, and NRF2. In an in vivo, AA extract significantly improved motor performance in rotarod, open field, and grid hanging tests. Biochemical assays showed reduced MDA and restored catalase and antioxidant levels. Dopamine, BDNF, GDNF, and LRRK2 levels increased significantly with treatment, confirming neuroprotective effects. AA-200 mg/kg dose was most effective, often comparable to levodopa, supporting its potential in Parkinson’s disease therapy.

Conclusion

A. agallocha is rich in bioactive compounds, including Clemiscosin D, 12-deoxyphorbol-13, a phorbol, which are known for their potent antioxidant and anti-inflammatory properties, and exerts neuroprotective effects by modulating key molecular targets involved in oxidative stress.