Nutrients
The Role of Herbal Medicines in Cognitive Impairment: A Narrative Review of Neuroprotective Mechanisms and Therapeutic Perspectives
By Aekkhaluck Intharuksa, Anchalee Prasansuklab, Tachpon Techarang and 3 others.
Abstract
Cognitive impairment encompasses a clinical spectrum ranging from mild cognitive impairment to dementia, particularly Alzheimer’s disease (AD), and involves interconnected pathological processes including cholinergic dysfunction, oxidative stress, neuroinflammation, mitochondrial impairment, amyloid-β accumulation, tau hyperphosphorylation, and synaptic loss. Herbal medicines have attracted increasing attention because their complex phytochemical composition may provide multi-target neuroprotective effects. This narrative review aimed to summarize current preclinical and clinical evidence on herbal medicines and traditional herbal formulations for cognitive impairment, with emphasis on their mechanisms, therapeutic potential, safety, and translational limitations. Relevant evidence from in vitro studies, animal models, randomized clinical trials, systematic reviews, and meta-analyses was narratively synthesized. The review considered single herbal medicines, standardized extracts, isolated phytochemicals, and traditional multi-herbal formulations, together with their reported cognitive outcomes and molecular targets. Preclinical studies suggest that selected herbal preparations may modulate pathways implicated in cognitive impairment through acetylcholinesterase and butyrylcholinesterase inhibition, antioxidant and mitochondrial protection, suppression of neuroinflammatory signaling, modulation of amyloidogenic and tau-related pathways, and enhancement of BDNF/TrkB- and CREB-associated neuroplasticit; however, clinical evidence remains limited and heterogeneous. Clinical studies of Bacopa monnieri, Panax ginseng, Crocus sativus, and several traditional Chinese, Korean, and Persian formulations have reported improvements in memory and global cognitive measures, including MMSE, MoCA, and ADAS-cog scores. However, evidence remains constrained by heterogeneity of products, small sample sizes, short treatment periods, inconsistent outcome measures, limited biomarker integration, and incomplete long-term safety assessment. Herbal medicines show potential as preventive, complementary, or adjunctive approaches for cognitive impairment, but they cannot yet be considered established replacements for conventional therapy. Standardized products, rigorous pharmacokinetic and toxicological evaluation, disease-relevant models, and adequately powered multicenter trials are required to support evidence-based clinical application.



