Yokukansan (Japanese name) is a medicine inspired by the original Chinese formulation Yi-Gan San. Both of them use the same characters, 抑肝散, they are traditional Asian herbal medicines. Yokukansan (YKS) contains an exactly measured 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). 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. Note of caution: the Chinese TCM corresponding formula Yi-Gan San, is not identical to YKS, it is merely inspired by it, despite using the same Kanji (this is true of all Kampo). There are many factors which make them different and therefore one may not substitute the corresponding TCM formulation and expect the same results -- from growing methods to processing to formulation to regulations.
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History
The original Chinese formula was first described in 保嬰撮要 (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.
Clinical evidence
In 2005, Iwasaki et al. (Japan) reported that YKS improved behavioral and psychological symptoms in dementia (BPSD), such as hallucination, delusion, agitation, and aggression. 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. Mizukami et al. (2009) reported their expanded crossover trial of the effects of YKS on BPSD. Finally, a meta-analysis showed the YKS effects on BPSD.
Shinno et al.reported that YKS was effective for control of psychiatric symptoms and improvement of sleep structure in patients with BPSD. Miyaoka et al. reported that YKS successfully treated neuroleptic-induced tardive dyskinesia and borderline personality disorder. Satoh et al. have also recently reported that YKS improved involuntary movements in Huntington’s disease. These clinical reports suggest that YKS has an antipsychotic like effect without causing extrapyramidal symptoms. Yokukansan had the effect on hyperkinesis of ADHD and Autism.
Pharmacological mechanisms
Sekiguchi et al. (2009) demonstrated that administration of YKS ameliorated aggressive behavior in mice injected with beta amyloid protein. 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. 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. 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. 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. 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 (an animal model of Alzheimer's disease), 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. 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. 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. 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).