Magnolol confers neurotrophic effects against MPTP/p-induced Parkinson's disease in mice via anti-inflammatory, anti-apoptotic mechanisms and PI3K/AKT/GSK3β/MAPK/mTOR signalling regulation.

The current hypothesis investigated the neurotrophic effect of magnolol (ML) against MPTP/p-induced neurotoxicity in Parkinson's disease (PD) mice, focusing on the molecular mechanisms of PI3K/Akt/GSK3β and MAPK signalling pathways. To determine the effective dose, 6 mice/group were employed for the dose-dependent study and brain-protective study. Behavioural deficits (open field test, narrow beam walking), dopamine (DA) depletion, lipid peroxidation, antioxidant levels, histology (H&E, PAS, and MT), inflammatory cytokines, DAT and VMAT2 expressions, SN region expressions of BDNF, GDNF, VEGF, and TrkB, RT-PCR of p38, MAPK, ERK, and JNK, and GSK3β/mTOR/PI3K/Akt signalling protein marker expression were evaluated. After 5 weeks of ML therapy, motor impairment significantly decreased, and lipid peroxidation, antioxidant levels, and inflammatory cytokines were restored. ML increased tropomyosin receptor kinase B (TrkB) expression, dopamine insufficiency, and MPTP/p-induced neurotrophic factors. ML therapy significantly decreased mRNA activation associated with MAPK/p38/JNK. Furthermore, ML increased PI3K, Akt, GSK3β, and mTOR phosphorylation, suggesting ML controlled the PI3K/Akt/mTOR signalling pathway. Altogether, this study offers a more thorough examination of the brain-protective effect of ML on dopaminergic neurons when combined with chronic PD. Additionally, it brings up the possibility of using ML as a new preventive and therapeutic drug. Study limitations include use of an acute MPTP/p model rather than progressive PD, absence of pharmacokinetic data, and no pathway confirmation using inhibitors. Long-term efficacy and clinical translation require further investigation.