Neuroprotective Potential of Terpenoids: A Promising Avenue in Neurology.
TL;DR
Terpenoids have the potential to be developed as novel multitarget neurotherapeutic agents with further research to bridge preclinical promise and clinical validation, and structural optimisation and advanced delivery systems, such as nanoparticles, cyclodextrin inclusion, combined therapeutic strategies, precision-targeted interventions, and rigorous clinical trials are considered future directions.
Abstract
Neurodegenerative diseases are progressive disorders characterised by the deterioration of neuronal structure and function, ultimately leading to cognitive deficits and functional impairment. Due to neuroinflammation, oxidative stress, and mitochondrial dysfunction, neurones, which cannot regenerate themselves, are highly susceptible to degeneration. There are many possible side effects associated with traditional pharmacotherapies, although they often offer symptomatic relief, highlighting the need for safer and more effective therapeutics. Natural products such as terpenoids, a structurally diverse class of isoprenoid compounds, have shown promising neuroprotective effects. Classes of terpenoids exhibit anti-inflammatory, antioxidant, anti-apoptotic, and mitochondrialprotective effects by regulating crucial signalling cascades, including Nuclear Factor kappa B (NF- κB), Mitogen-activated protein kinase (MAPK), c-Jun N-terminal Kinase (JNK), Phosphoinositide 3-kinase/Protein kinase B (PI3K/Akt), and Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1). Across preclinical models, representative compounds like catalpol, geniposide, artesunate, ginkgolides, alisol A 24-acetate, echinocystic acid, lycopene, and astaxanthin have demonstrated efficacy against Parkinson's disease, Alzheimer's disease, stroke, ischaemia, and haemorrhage by preserving neuronal integrity and function. Despite these promising findings, challenges such as poor bioavailability, limited blood-brain barrier penetration, metabolic instability, and a lack of standardised human safety data limit translational progress. Structural optimisation and advanced delivery systems, such as nanoparticles, cyclodextrin inclusion, combined therapeutic strategies, precision-targeted interventions, and rigorous clinical trials, may be considered future directions. In short, terpenoids have the potential to be developed as novel multitarget neurotherapeutic agents with further research to bridge preclinical promise and clinical validation.