Memory and learning-enhancing effect of Daikenchuto, a traditional Japanese herbal medicine, in mice

Abstract

The effect of Daikenchuto (DKT), a traditional Japanese herbal medicine (Kampo medicine), and its constituents (ginger rhizome, ginseng root, rice gluten and Zanthoxylum fruit) on the memory formation process was examined in mice by means of a Morris water maze test. The administration of DKT [300-4000 mg/ kg, administered orally (p.o.)] for 3 consecutive days dose-dependently shortened the time required by the mice to find the platform in the water maze test relative to the control. Among the four constituents of DKT, the extract of Zanthoxylum fruit (70 mg/kg, the dose equivalent to 4000 mg/kg DKT) administered p.o. for 3 consecutive days significantly promoted the memory and learning rate. The memory-and learning-enhancing effect was potently elicited by 5 mg/kg (p.o., 2 days) hydroxy-sanshool, the active component of the ethyl acetate fraction of Zanthoxylum fruit. In another series of experiments with the water maze test, the administration of scopolamine [1 mg/kg, intraperitoneally (i.p.)] for 3 consecutive days significantly prolonged the time needed by the mice to find the platform. The subsequent administration of DKT (4000 mg/kg, p.o.) for 3 consecutive days possessed an abatement effect on the scopolamine-induced dementia. The present results indicate that DKT and, more specifically, its constituent Zanthoxylum fruit and the active component of Zanthoxylum fruit, hydroxy-sanshool, all have a memory-and learning-enhancing effect and are probably associated with the release of acetylcholine from neuronal terminals in the brain.

The Acute and Chronic Cognitive and Cerebral Blood-Flow Effects of Nepalese Pepper (Zanthoxylum armatum DC.) Extract—A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Humans

“…In terms of mechanisms underpinning the effects seen in the current study, previous research suggests that both the gastrointestinal effects of Daikenchuto, which contains hydroxy-alpha-sanshool from Z. piperitum [13] and the learning and memory effects of ZA in rodents [12] may be underpinned by increased cholinergic activity. Indeed, monoterpenes, which are represented in ZA extracts at significant levels, have been shown to have consistent cholinesterase inhibitory properties [36,37] and to exert beneficial cognitive effects [20]; including at doses as low as 25 µL [38].…”

“…In mechanistic terms, the gastrointestinal effects of Daikenchuto have been attributed to increased acetylcholine release [13]. In line with this, an attenuation of the learning and memory decrements associated with scopolamine in rodents suggests cholinergic activity as a potential mechanism of any brain function effects of Daikenchuto and its active ingredients [12]. However, it is also notable that alkamides such as γ-sanshool have been shown to interact with cannabinoid CB 1 and CB 2 receptors; due to the structural similarity between the sanshool group and endocannabinoids [14].…”

“…Its bioavailability peaked after 30 min with a mean half-life of approximately 2 h [11]. A single study [12] demonstrated that Daikenchuto, administered for 3 days, improved mouse learning and memory and attenuated the cognitive decrements associated with the muscarinic receptor antagonist scopolamine. The learning and memory effects were also evident following both the ZA and hydroxy α-sanshool components by themselves, confirming that hydroxy α-sanshool was the active component in terms of learning and memory benefits.…”

Brahmi (<italic>Bacopa monnieri</italic>): Up-to-date of memory boosting medicinal plant: A review

“…Currently available drug treatments decelerate the progression of the disease, provide symptomatic relief, but fail to achieve a definite cure (Connolly and Lang, 2014;Kumar and Ekavali, 2015). There are a number of foods (plants, herbs, fruits, and vegetables) and supplements that are known to enhance the brain activity as "Memory Boosting Foods or Supplements" (Othman et al, 2015;Venkatesan et al, 2015) for the example Indian traditional memory enhancing herbs (Bhowmik et al, 2010;Jatwa et al, 2014), Chinese traditional memory enhancing herbs (Ho et al, 2005), Korean East Asian traditional cognitive impairment herbs (Kumar et al, 2013), Japanese traditional memory and learning-enhancing herbs medicine (Nakamura et al, 2006), Europe traditional cognitive impairment herbs (Eckert, 2010). According to the National Medicinal Plants Board report, the annual market demand for Brahmi, Bacopa monnieri is around 1,000 tones in year 2000, which increased many fold due to its potential uses in Ayurvedic medicine to treat variety of diseases (Tripathi et al, 2012).…”

Message from the chief editor

“…From volume 60 (2006), two papers concerning an opioid agonistic alkaloid [1] and the pharmacology of a Kampo formula [2] were given awards. Selection of Excellent Papers from volume 61 is currently in progress, and the results will be announced soon.…”