Compositions Yi-Gan San and Alzheimer's disease

Posted by Chantel Martiromo 

Alzheimer's disease is a brain disorder correlated with major reductions of neurons to the respective target areas and named after German physician Alois Alzheimer. Alzheimer's destroys brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal. 
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease. It may be results of  cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity)(1) Strong evidences emerged in epidemiological studies suggested that certain herbs(2) may have potential in reduced risk and treatments of Alzheimer's disease but geographic source of the plant material, climatation, and time of harvest may effect their effectiveness. It is understandable that commercially available herbal medicinal products with the same herbal ingredients vary in their content and concentration of chemical constituents when compared between manufacturers.

Yi-Gan San also known as Yokukansanin Japan, is a Bupleurum Formula consisting Chai Hu,  Fu Ling,  Chuan Xiong, Gan Cao, Dang Gui, Gou Teng and Cang Zhu. The composition has been used in traditional Chinese medicine for treatment of calm impatience, difficulty falling asleep or staying asleep.
Yi-Gan San exhibited a clinically significant decrease in terms of hallucinations, agitation, anxiety, irritability or abnormal behavior(44)(45) and improved behavioral and psychological symptoms of dementia (BPSD) and activities of daily living (ADL)(46). In olfactory bulbectomized (OBX) mice, The composition reversed spatial working memory and non-spatial working memory impairments, through reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M1 receptor expression without affecting muscarinic M₃ receptor expression or AChE activity(47). But the Kanto Central Hospital study reported a case of 81 years of age patient with symptoms of metabolic alkalosis with hypokalemia, due to intake of Yokukansan for 6 months(48). 

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References
(1) Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. by Qiu C, Kivipelto M, von Strauss E.(PubMed)
(2) The Use of Herbal Medicine in Alzheimer's Disease—A Systematic Review by Leopoldo Luiz dos Santos-Neto,¹ Maria Alice de Vilhena Toledo,²
(44) Treatment of behavioral and psychological symptoms of Alzheimer-type dementia with Yokukansan in clinical practice by Hayashi Y, Ishida Y, Inoue T, Udagawa M, Takeuchi K, Yoshimuta H, Kiue K, Ninomiya Y, Kawano J, Sameshima T, Kawahara T, Goto I, Shudo K, Kurayama S, Nakamura J, Okahara K, Mitsuyama Y.(PubMed)
(45) Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease by Okahara K, Ishida Y, Hayashi Y, Inoue T, Tsuruta K, Takeuchi K, Yoshimuta H, Kiue K, Ninomiya Y, Kawano J, Yoshida K, Noda S, Tomita S, Fujimoto M, Hosomi J, Mitsuyama Y.(PubMed)
(46) 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 by Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, Tanji H, Fujiwara H, Seki T, Fujii M, Arai H, Sasaki H.(PubMed)
(47) Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice by Yamada M, Hayashida M, Zhao Q, Shibahara N, Tanaka K, Miyata T, Matsumoto K.(PubMed)
(48) [A case of severe hypokalemia caused by a Chinese herbal remedy (Yokukansan) in an 81-year-old woman with dementia].[Article in Japanese]by Nishiyama N, Takeshita M, Tanaka K, Miyao M, Mizuno Y.(PubMed)