Current Utilization and Research Status of the Herbal Medicine Guibi-Tang and Its Variants for Cognitive Impairment:...

Background/Objectives: Guibi-tang (GBT) and its variant Kami-guibi-tang (KGBT) are traditional East Asian multi-herb formulas prescribed for memory loss, insomnia, and fatigue. Preclinical data suggest multimodal neuroprotective actions, including cholinergic signaling modulation and activation of the cAMP response element-binding protein (CREB)/extracellular signal-regulated kinase (ERK) pathway; however, clinical evidence for cognitive disorders remains scattered. This scoping review aimed to map the breadth, design characteristics, efficacy signals, and safety profile of GBT and KGBT across the full spectrum of cognitive impairment. Methods: Following the Arksey-O'Malley framework and PRISMA-ScR guidelines, seven databases were searched (MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, ScienceON, Scopus, Citation Information by the National Institute of Informatics) from inception to 31 January 2025, for human studies evaluating GBT or KGBT in subjective cognitive decline, mild cognitive impairment (MCI), dementia, or post-stroke cognitive impairment (PSCI). Two reviewers independently screened, extracted, and charted data on study design, participants, interventions, outcomes, and adverse events. Results: Fifteen studies met the inclusion criteria-nine randomized controlled trials, one crossover trial, and five observational reports-enrolling 555 participants (age range, 59-87 years). All were conducted in the Republic of Korea, Japan, or China. GBT or KGBT, given as monotherapy or adjunctive therapy for 4 weeks to 9 months, produced modest but consistent improvements in global cognition (Mini-Mental State Examination/Montreal Cognitive Assessment), memory domains, activities of daily living, and neuropsychiatric symptoms across MCI, Alzheimer's disease, and PSCI cohorts. Reported adverse event rates were comparable to or lower than those of placebo, usual care, or conventional drugs, and no serious treatment-related toxicity was identified. Conclusions: Current evidence-although limited by small sample sizes, heterogeneous formulations, short follow-up durations, and regional concentration-indicates that GBT and KGBT are well tolerated and confer clinically meaningful cognitive and functional benefits. Standardized, multicenter, placebo-controlled trials with biomarker end points are warranted to confirm long-term efficacy, clarify mechanisms, and guide integrative clinical use.