Kihito, a Traditional Japanese Kampo Medicine, Improves Cognitive Function in Alzheimer’s Disease Patients

Abstract

Background and Aims. We previously reported that the administration of traditional Japanese medicines, kihito (Gui-Pi-Tang in Chinese) and kamikihito (Jia-Wei-Gui-Pi-Tang in Chinese), to Alzheimer’s disease (AD) model mice improved memory impairment. There are a few reports that show kihito and kamikihito have a beneficial effect on the cognitive function of AD patients in clinical studies. However, these studies are not comparative and are retrospective studies; thus, more evidence is needed. Therefore, we conducted an open-label, crossover designed clinical trial to investigate the effect of kihito on cognitive function of AD patients. Methods. The inclusion criteria for eligible patients were as follows: (1) imaging diagnosis (magnetic resonance imaging and single-photon emission computed tomography) of AD, (2) a treatment regimen including acetylcholinesterase inhibitors (ChEIs), and (3) a Mini-Mental State Examination (MMSE) score ≥15. The exclusion criteria were as follows: (1) change in ChEI dosage, (2) memantine usage, and (3) MMSE score < 15. To prevent bias in age and baseline cognitive function, patients were divided into two groups: the first group received 2.5 g of kihito extract 3 times/day during the first half of the study (weeks 0-16) and the second group received the same dose of kihito during the second half of the study (weeks 17-32). ChEI dosage did not change during the study period. Patients underwent a cognitive function test during weeks 0, 16, and 32. Cognitive function was evaluated by Japanese versions of the Mini-Mental State Examination (MMSE-J) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS-J) test. Results. Ten patients completed the clinical trial (4 males, 6 females, average age 71.7 years). MMSE-J scores significantly increased during the kihito intake period. RBANS-J test scores had a slight improvement during the kihito intake period compared with the ChEI alone treatment period, but no significant changes were observed. Conclusion. Kihito improves cognitive function in AD patients.

Korean Traditional Medicine in Treating Patients with Mild Cognitive Impairment: A Multicenter Prospective Observational Case Series

“…Bojungikgi-tang showed antidementia and neuroprotective effect in Aβ-injected mice [50] and improved the symptoms of vascular dementia in some case reports [51,52]. Also, Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) showed the effect on memory deficit induced by Aβ [53] and improved cognitive function in patients with Alzheimer's disease [54] in previous studies. In tonifying kidney formulae, a number of studies of tonifying kidney (Bushen in Chinese) formula for cognitive impairment have been reported, mainly concentrated in China [8,10,11,55].…”

The efficacy and safety of hachimijiogan for mild Alzheimer disease in an exploratory, open standard treatment controlled, randomized allocation, multicenter trial

“…In addition to HJG, it has been reported that the Kampo medicines kihito and ninjinyoeito improve the cognitive function of AD patients. [ 15 , 19 ] However, all of the previous studies used MMSE to estimate cognitive function. Advanced cognitive function tests such as ADAS-cog will be necessary to make a more accurate evaluation, thus we set the change of ADAS-Jcog as the primary endpoint.…”

Impacts of Drug Interactions on Pharmacokinetics and the Brain Transporters: A Recent Review of Natural Compound-Drug Interactions in Brain Disorders

“…Moreover, this co-administration can more improve cognitive function in AD patients via pharmacodynamics NDIs, but the exact mechanism is still unknown [63]. In a similar way, co-administration of kihito extract, a traditional Japanese kampo medicine composed of Ginseng Radix, Polygalae Radix, Astragali Radix, Zizyphi Fructus, Zizyphi Spinosi Semen, Angelicae Radix, Glycyrrhizae Radix, Atractylodis Rhizoma, Zingiberis Rhizoma, Poria, Saussureae Radix, and Longan Arillus and ChEIs can also more improve cognitive function in AD patients compared to single ChEI treatment, but still exact mechanism should be addressed through further study [64].…”