Blood–Brain Barrier Modulation By Herbal Compounds: Implications For Neuroprotection

Abstract

The blood–brain barrier (BBB) is a highly selective physiological interface that regulates the passage of molecules into the central nervous system (CNS). While this barrier is essential for neuronal protection, it poses a major challenge for drug delivery in treating neurodegenerative and neuropsychiatric disorders. Recent advances highlight the potential of herbal compounds, many of which possess neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic properties, to cross or modulate the BBB. Compounds such as withanolides, bacosides, ginsenosides, and flavonoids have demonstrated significant roles in enhancing cognitive function, reducing oxidative stress, modulating neurotransmitter systems, and protecting synaptic integrity. Pharmacokinetic features such as lipophilicity, molecular size, and interactions with efflux transporters strongly influence their BBB permeability. Preclinical and clinical studies support their therapeutic promise in conditions including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy, and mood disorders. Furthermore, synergistic approaches employing nanocarriers or combined herbal–synthetic therapies show potential for overcoming delivery challenges and maximizing therapeutic efficacy. Despite encouraging outcomes, critical issues remain regarding dose optimization, herb–drug interactions, and standardization of herbal extracts. Future directions point toward advanced herbal nanosystems, omics-based exploration, and AI-driven screening for identifying BBB-active compounds, along with addressing regulatory and translational hurdles. Overall, herbal compounds offer a promising and multi-targeted strategy for BBB modulation and neuroprotection, warranting further scientific validation for clinical translation.