Abstract
Hallucinations are a common non-motor symptom of Parkinson’s disease and various forms of dementias. Yokukansan and Yokukansankachimpihange have attracted attention due to their effectiveness in the treatment of hallucinations of dementia. To clarify which component in these formulas contribute to the effects, at first, we focused on their differences in compositions to examine the pharmacological effects on the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head-twitch response (HTR) in mice that has been used as animal hallucination model. Results indicated that water extract of Byaku-jutsu (Atractylodes japonica) showed a stronger inhibitory effect on DOI-induced HTR than that of So-jutsu (A. lancea) corresponding to their major constituents of atractylenolide III and β-eudesmol, and suggested that the major constituents should be active constituents contributing to the antihallucination effects of Byaku- and So-jutsu. Besides, the part B–C ring (butenolide) in atractylenolide III was found to be similar to the structure of serotonin and suggested that the B–C ring may partially play role in antagonistic activity against serotonin receptors. Thus, a novel, rational design of butenolide-related compounds may as potential lead compounds for new drug development. Analysis of the chemical components of Byaku- and So-jutsu and further study on their structure-activity relationships are currently in progress.
Highlights
Hallucinations are a common non-motor symptom of Parkinson’s disease and various forms of dementias such as Alzheimer’s disease and the lewy body dementias [1]
In the course of a study to clarify which components contribute to the effects on hallucination induced by DOI in mice between two Kampo formulas, Yokukansan and YKH, we found that “Jutsu”
To know whether the major constituents contribute to their pharmacological effects, atractylenolide III and β-eudesmol were evaluated and it was found that both showed significant effects against DOI-induced head-twitch response (HTR)
Summary
Hallucinations are a common non-motor symptom of Parkinson’s disease and various forms of dementias such as Alzheimer’s disease and the lewy body dementias [1]. In the Japanese pharmacopoeia “Jutsu” is traditionally divided into “Byaku-jutsu” (Atractylodis rhizome) and “So-jutsu” (Atractylodis lanceae rhizome), which are defined as the rhizome of Atractylodes japonica Koidzumi ex Kitamura, or the rhizome of A. ovata De Candolle and A. lancea De Candolle, and A. chinesis Koidzumi or their interspecific hybrids, according to their different applications [10] The former as a qi (energy)-invigorator, and the latter as an aromatic dampness-transforming medicine, and are usually used for treatment of psychological, immunologic and digestive disorders. We report the pharmacological effects of water extracts of Byaku-jutsu (A. japonica Koidzumi ex Kitamura) and So-jutsu (A. lancea De Candolle) on DOI-induced HTR in normal mice. These constituents contribute to the pharmacological effects, because atractylon is an excessively unstable sesquiterpenoid in Byaku-jutsu, which is converted into atractylenolide II, and atractylenolide III in particular [11,12]
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