The Neuroprotective Potential of Panax ginseng in Neurodegenerative Diseases: Molecular Mechanisms, Therapeutic Evidence, and Translational Perspectives

Neurodegenerative disorders, encompassing Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Huntington’s disease (HD), constitute a major and escalating public health burden in ageing societies worldwide. These conditions are defined by the progressive degeneration and loss of specific neuronal populations, resulting in profound cognitive decline, motor disability, and behavioural disturbances that severely compromise patient autonomy and quality of life. Existing pharmacological interventions remain predominantly symptomatic, failing to modify underlying disease trajectories or halt neuronal demise. Consequently, there is an urgent imperative to identify novel disease-modifying agents capable of targeting the multifaceted pathophysiological cascades that characterise these disorders.

Panax ginseng, a cornerstone of traditional East Asian medicine, has attracted considerable contemporary interest owing to its established adaptogenic profile and emerging evidence of potent neuroprotective activity. The primary pharmacologically active constituents of ginseng are ginsenosides – a diverse class of steroidal saponins – which exert pleiotropic effects including robust antioxidant, anti-inflammatory, and anti-apoptotic actions. These properties position ginsenosides as promising candidates for counteracting the convergent pathogenic mechanisms operative across multiple neurodegenerative entities, notably oxidative stress, aberrant protein aggregation, mitochondrial bioenergetic failure, and neuroinflammatory activation.

In models of Alzheimer’s disease, ginsenosides have been demonstrated to attenuate core neuropathological hallmarks. Specifically, ginsenoside Re reduces cerebral amyloid-β (Aβ) generation through PPARγ-mediated suppression of β-secretase (BACE1) activity in N2a/APP695 neuronal cultures (Cao et al., 2016). Complementary investigations reveal inhibition of tau hyperphosphorylation and associated functional perturbations of microtubule dynamics (Alonso et al., 2018), collectively suggesting disease-modifying potential in the Alzheimer’s continuum.

In Parkinson’s disease paradigms, multiple ginsenosides confer protection to dopaminergic neurons within the substantia nigra pars compacta. Ginsenoside Rg1 mitigates dopamine-induced oxidative injury and apoptosis in PC12 pheochromocytoma cells (Chen et al., 2003), whereas the same compound attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral neuron loss in vivo via suppression of oxidative stress (Chen et al., 2005). Furthermore, ginsenoside Rb1 inhibits α-synuclein fibrillization, neutralises oligomer toxicity, and promotes disaggregation of pre-formed fibrils – actions that may retard Lewy body pathogenesis (Ardah et al., 2015).

Emerging preclinical data also support therapeutic relevance in other neurodegenerative contexts. In amyotrophic lateral sclerosis and Huntington’s disease models, ginseng-derived compounds enhance motor performance, prolong neuronal survival, and ameliorate cellular toxicity. Analogous beneficial effects on motor function and inflammatory demyelination have been reported in experimental autoimmune encephalomyelitis, the principal animal model of multiple sclerosis.

In aggregate, the neuroprotective efficacy of Panax ginseng appears to arise from its capacity to simultaneously modulate several interdependent pathological cascades that drive neurodegeneration. By attenuating oxidative damage, inhibiting pathological protein aggregation, preserving mitochondrial integrity, and dampening neuroinflammation, ginsenosides address the molecular convergence points shared by disparate neurodegenerative diseases.

The translational trajectory of Panax ginseng from bench to bedside necessitates rigorous future investigation. High-priority research avenues include systematic evaluation of individual ginsenoside congeners, elucidation of precise molecular targets and signalling pathways, optimisation of bioavailability through novel delivery systems, and execution of adequately powered, randomised, placebo-controlled clinical trials across well-characterised patient cohorts. Successful navigation of these milestones may ultimately establish ginseng-derived interventions as valuable components of future multimodal therapeutic strategies for neurodegenerative disorders.