Intranasal Herbal Neurotherapeutics in Neurodegenerative Disorders: Preclinical Advances and Translational Implications

Abstract

Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease represent major global health challenges characterized by progressive neuronal loss, neuroinflammation, oxidative stress, and cognitive and motor dysfunction. Despite advances in modern neuroscience, existing therapies remain largely symptomatic, with limited disease-modifying efficacy, partly due to restricted blood-brain barrier (BBB) penetration and long-term safety concerns. Intranasal delivery has emerged as a promising complementary strategy for central nervous system targeting by exploiting olfactory and trigeminal neural pathways to bypass the BBB. This review critically evaluates intranasal delivery of Indian traditional herbal medicines for neurodegenerative disorders, integrating perspectives from Ayurveda, Siddha, and Unani systems with contemporary preclinical and translational research. Herbal interventions, including whole plant extracts (e.g., Bacopa monnieri, Centella asiatica) and isolated phytochemicals (e.g., withanolides from Withania somnifera, curcuminoids from Curcuma longa) incorporated into experimental intranasal and nanoformulations, demonstrate multimodal neuroprotective actions. These include modulation of neuroinflammatory pathways, attenuation of oxidative stress, stabilization of mitochondrial function, and enhancement of synaptic plasticity. Advances in intranasal nanotechnology, particularly nanoparticle-based and mucoadhesive delivery systems, have improved phytoconstituent bioavailability, nasal residence time, and brain targeting efficiency. However, clinical evidence remains limited, and challenges related to extract standardization, long-term safety, pharmacokinetics, and regulatory approval persist. Overall, intranasal herbal therapy represents a promising translational strategy that warrants rigorous clinical validation before routine clinical application.