Seabuckthorn Bioactive Compounds in Neuroprotection: Phytochemistry, Pharmacological Mech

Abstract

Neurodegenerative diseases, particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent major global health challenges associated with progressive neuronal dysfunction, cognitive decline, oxidative stress, mitochondrial impairment, neuroinflammation, protein aggregation and synaptic dysfunction. The complex and multifactorial nature of these disorders has stimulated increasing interest in multi-target therapeutic strategies based on naturally occurring bioactive compounds. Seabuckthorn (Hippophae rhamnoides L.), a medicinal and nutritionally important plant belonging to the family Elaeagnaceae, is a rich source of phenolic acids, flavonoids, proanthocyanidins, carotenoids, vitamins, fatty acids, triterpenoids, phytosterols and other secondary metabolites. Among these constituents, phenolic compounds including quercetin, kaempferol, isorhamnetin, gallic acid, ellagic acid, protocatechuic acid and ferulic acid have attracted particular interest because of their antioxidant, antiinflammatory, anti-apoptotic and neuroprotective properties. Experimental studies indicate that seabuckthorn extracts and selected constituents can attenuate oxidative injury, regulate inflammatory signaling, protect neuronal cells, influence neurotrophic pathways and improve cognitive performance in experimental models. Seabuckthorn flavonoids have been associated with regulation of PI3K/Akt and ERK signaling, while isorhamnetin has demonstrated antioxidant and anti-inflammatory effects in experimental models. However, the therapeutic translation of these compounds is limited by poor aqueous solubility, chemical instability, extensive metabolism, low systemic bioavailability and restricted penetration across the blood–brain barrier (BBB). Nanotechnologybased drug delivery systems, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, nanoemulsions, phytosomes and exosome-based systems, may provide opportunities to improve stability, pharmacokinetics, cellular uptake and brain delivery. This review summarizes the botanical and phytochemical characteristics of H. rhamnoides, with particular emphasis on neuroactive phenolics; discusses potential molecular mechanisms underlying neuroprotection; evaluates available experimental evidence in neurodegenerative and cognitive disorders; and examines nanotechnology-based approaches for improving delivery of seabuckthorn bioactives to the central nervous system. Particular attention is given to liposomal delivery of total phenolics as a prospective strategy for improving bioavailability and therapeutic performance. Although current evidence is promising, systematic characterization, standardized extracts, pharmacokinetic studies, BBB transport studies, toxicological evaluation and well-designed clinical trials are required before seabuckthorn phenolics can be considered established therapeutic agents for neurodegenerative diseases.