Alpha‐Linolenic Acid for Mitigating Neuroinflammation and Dopaminergic Neuronal Loss in Parkinson's Disease: Insights From In Vivo and In Silico Studies

作者：Mahnoor Mahnoor, Sarwat Jahan, L Razavi Nemat Elahi, Muhammad Zakria, Rabia Rabia, Muhammad Aimen Ikram, Najeeb Ullah · 发表于：Clinical and Experimental Pharmacology and Physiology · 年份：2025 · DOI：10.1111/1440-1681.70043 · 被引用次数：6 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Nuclear Receptors and Signaling、Neuroinflammation and Neurodegeneration Mechanisms

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by dopaminergic neuronal loss and chronic neuroinflammation, leading to significant motor and non-motor deficits. This study explores the therapeutic potential of alpha-linolenic acid (ALA), a known antioxidant and anti-inflammatory agent, in a lipopolysaccharide (LPS)-induced murine model of PD. Male Balb-C mice were divided into control, LPS-treated, LPS + ALA-treated and ALA-only groups. Behavioural assessments, including the pole test, rotarod test and open field test, revealed significant motor impairments in LPS-treated mice. Co-treatment with ALA partially ameliorated motor deficits in LPS-treated mice compared to the healthy control group. However, no direct comparison was made with standard PD treatments such as levodopa. Immunohistochemistry analysis showed a 68% reduction in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra pars compacta (SNpc) of LPS-treated mice. Notably, ALA co-treatment preserved dopaminergic neurons, demonstrating its neuroprotective effects. Western blotting and ELISA revealed heightened expression of inflammatory mediators, including TNF-α, IL-1β and NF-κB, in LPS-treated mice. ALA treatment significantly reduced these markers, indicating its capacity to mitigate neuroinflammation. Molecular docking analysis revealed moderate binding affinities of ALA to NF-κB (-5.1 kcal/mol), TNF-α (-5.7 kcal/mol) and IL-1β (-3.9 kcal/mol), suggesting possib...