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Yokukansan

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Yokukansan　(in Japan), Yi-Gan San　(in China) or 抑肝散 is a traditional Asian herbal medicine.[1] It was originally described in 保嬰撮要[2] (Bâo yïng cuö yào, Synopsis for Protecting Infant) written by 薛鎧(Xue Kai) and 薛己 (Xue ji, a son of Xue Kai) in Ming dynasty China 1555 or 1556 as a remedy for restlessness and agitation in children.[3] Yokukansan (YKS) contains a mixture of dried herbs, 4 g of Atractylodis lanceae rhizoma (蒼朮), 4 g of Poria (伏苓), 3 g of Cnidii rhizoma (川芎), 3 g of Angelicae radix (当帰), 2 g of Bupleuri radix (柴胡), 1.5 g of Glycyrrhizae radix (甘草), and 3 g of Uncariae uncis cum ramulus (釣藤鈎)[4]. These herbs are registered in the Pharmacopoeia of Japan ver. 15. Patients take 2.5 g of YKS powder (1.08 g extract) three times a day. YKS has been approved by the Ministry of Health, Labour and Welfare (Japan) as prescriptions covered under the National Health Insurance plan.

Clinical evidence

In 2005, Iwasaki et al. (Japan) reported that YKS improved Behavioral and psychological symptoms such as hallucination, delusion, agitation and aggression in dementia (BPSD)[5]. Since then, many studies showing the effects and mechanisms of YKS on psychosomatic and neurological symptoms have been published as below. Iwasaki et al. reported a 15 dementia with Lewy bodies (DLB) patient case series where hallucinations and other BPSDs were successfully improved with YKS treatment[6]. Mizukami et al. (2009) reported their expanded crossover trial of the effects of YKS on BPSD[7].
Shinno et al.reported that YKS was effective for control of psychiatric symptoms and improvement of sleep structure in patients with BPSD[8]. Miyaoka et al. reported that YKS successfully treated neuroleptic-induced tardive dyskinesia[9] and borderline personality disorder[10]. Satoh et al. have also recently reported that YKS improved involuntary movements in Huntington’s disease[11]. These clinical reports suggest that YKS has an antipsychotic like effect without causing extrapyramidal symptoms.

Pharmacological mechanisms

Sekiguchi et al.[12] (2009) demonstrated that administration of YKS ameliorated aggressive behavior in A beta injected mice. Also, they demonstrated that YKS did not suppress motor activity, nor did it induce catalepsy. Takeda et al. (2008) pointed out that YKS attenuated abnormal glutamate release in rats on a diet deficient in zinc[13]. They also reported that YKS significantly suppressed the increase in extracellular concentrations of glutamate and aspartate seen in the hippocampus of zinc-deficient rats after stimulation with KCl[14]. Egashira et al. (2008) reported that YKS inhibited the 2,5-dimethoxy-4-iodoamphetamine-induced head-twitch response and decreased expression of 5-hydroxytryptamine 2A receptors in the prefrontal cortex[15]. Also, Terawaki K et al. reported partial agonistic effect of YKS on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells[16]. These reports suggest involvement of serotonergic and glutamatergic functions is the underlying mechanisms of YKS. Though Tabuchi et al. reported that YKS ameliorated cognitive disturbances in APP transgenic mice (animal model of AD)[17], the improvement of cognition with YKS was not clinically demonstrated. Shimada et al. (2001) reported that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae uncus cum ramulus, a herb in YKS, protected against glutamate-induced neuronal death in cultured cerebellar granule cells[18]. They suggested that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine were the active components of the Uncariae[19]. These compounds may cause the clinical effects of YKS. In 2012, Nishi et al. reported that at least some of the effects of YKS could be due to an alkaloid found in the hooks of Unicaria, geissoschizine methyl ether (GM), which acted as a partial agonist at the 5-HT1A receptor.[20] This data was supported by their concurrent finding that treatment with GM could reduce aggression and increase social behavior in socially isolated mice, while treatment with YKS that lacked Unicaria hooks could not.

Notice

YKS contains Glycyrrhizae radix, therefore care must be taken to avoid Potassium concentration. Glycyrrhizae radix sometimes causes hypokalemia (low potassium in the blood)[21].

See also

References

  1. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1248/bpb.32.1701, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1248/bpb.32.1701 instead.
  2. ^ http://www.eastlandpress.com/upload/2_pdf_1_20090602161407_1/1%20List%20Titles%20New.pdf
  3. ^ Clinical Potential of Yi-Gan San (Yokukansan) for the Treatment of Psychiatric Disorders
  4. ^ Iwasaki K, Satoh-Nakagawa T, Maruyama M et al. A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry 2005;66:248-252
  5. ^ =reference 3
  6. ^ Iwasaki K, Maruyama M, Tomita N et al. Effects of the traditional Chinese herbal medicine Yi-Gan San for cholinesterase inhibitor-resistant visual hallucinations and neuropsychiatric symptoms in patients with dementia with Lewy bodies. J Clin Psychiatry 2005;66:1612-1613
  7. ^ Mizukami K, Asada T, Kinoshita T et al. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol 2009;12:191-199
  8. ^ Shinno H, Inami Y, Inagaki T, et al. Effect of Yi-Gan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(3):881-885
  9. ^ Miyaoka T, Furuya M, Yasuda H, et al. Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(3):761-764
  10. ^ Miyaoka T, Furuya M, Yasuda H, et al. Yi-gan san for the treatment of borderline personality disorder: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(1):150-15
  11. ^ Satoh T, Takahashi T, Iwasaki K, et al. Traditional Chinese medicine on four patients with Huntington's disease. Mov Disord. 15 February 2009;24(3):453-5.
  12. ^ Sekiguchi K et al., Effects of yokukansan, a traditional Japanese medicine, on aggressiveness induced by intracerebroventricular injection of amyloid beta protein into mice. Phytother Res. 2009 Aug;23(8):1175-81.
  13. ^ Takeda A, Tamano H, Itoh H et al. Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan. Neurochem Int 2008b;53:230-235
  14. ^ Takeda A, Itoh H, Tamano H et al. Suppressive effect of Yokukansan on excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats. Nutr Neurosci 2008a;11:41-46
  15. ^ Egashira N, Iwasaki K, Ishibashi A et al. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1516-1520
  16. ^ Terawaki K et al.Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells.J Ethnopharmacol. 3 February 2010;127(2):306-12. Epub 11 November 2009.
  17. ^ Tabuchi M et al. Ameliorative effects of yokukansan, a traditional Japanese medicine, on learning and non-cognitive disturbances in the Tg2576 mouse model of Alzheimer's disease. J Ethnopharmacol. 25 February 2009;122(1):157-62. Epub 25 December 2008.
  18. ^ Shimada Y, Goto H, Kogure T et al. Protective effect of phenolic compounds isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death. Am J Chin Med 2001;29:173-180
  19. ^ Shimada Y, Goto H, Itoh T et al. Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats. J Pharm Pharmacol 1999;51:715-722
  20. ^ Nishi A et al. Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin(1A) receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan. Neuroscience. 2012 Apr 5;207:124-36.
  21. ^ Crean AM et al. A sweet tooth as the root cause of cardiac arrest. Can J Cardiol. 2009 Oct;25(10):e357-8.

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