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Ninjinyoeito, Hochuekkito, and Juzentaihoto are the three types of Kampo-hozai used to support the treatment of various diseases by energizing patients through improved mental health. While Kampo-hozais are clinically used to improve mental energy decline, a comparison between their effects on neuropsychiatric symptoms like anxiety and sociability and the strength of their effects has not been conducted. Therefore, this study compared the effects of Ninjinyoeito, Hochuekkito, and Juzentaihoto on psychiatric symptoms using neuropeptide Y knockout (NPY-KO) zebrafish, a suitable animal model for anxiety and low sociability. Neuropeptide Y knockout zebrafish were fed a Ninjinyoeito, Hochuekkito, or Juzentaihoto-supplemented diet for 4 days. Then, sociability was analyzed using a three-Chambers test and anxiety-like behavior was evaluated using the cold stress and novel tank tests. The results showed that Ninjinyoeito treatment improved the low sociability of neuropeptide Y knockout, while Hochuekkito and Juzentaihoto did not. Neuropeptide Y knockout exhibited anxiety-like behaviors, such as freezing and swimming in the wall area under cold stress, but Ninjinyoeito treatment improved these behaviors. However, these anxietylike behaviors were not improved by Hochuekkito and Juzentaihoto. Ninjinyoeito treatment also improved anxiety-like behaviors of neuropeptide Y knockout in the novel tank test. However, no improvement was shown in the Hochuekkito and Juzentaihoto groups. This trend was also confirmed in the low water stress test using wild-type zebrafish. This study exhibits that among the three types of Kampohozai, Ninjinyoeito is themost effective in psychiatric disorders associated with anxiety and low sociability. [ABSTRACT FROM AUTHOR]

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient's physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula–pattern pairings. The present study aims to develop such pairings. Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models. Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (大柴胡湯), Dai-joki-To (大承気湯), Shigyaku-San (四逆散), Saiko-ka-ryukotsu-borei-To (柴胡加竜骨牡蛎湯), Keishi-bukuryo-Gan (桂枝茯苓丸), Hachimi-jio-Gan (八味地黄丸), Hange-shashin-To (半夏瀉心湯), Sho-saiko-To (小柴胡湯), Hochu-ekki-To (補中益気湯), Sho-kenchu-To (小建中湯), Toki-shakuyaku-San (当帰芍薬散), Ninjin-To (人参湯), and Dai-kenchu-To (大建中湯). Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education. [ABSTRACT FROM AUTHOR]

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient’s physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula–pattern pairings. The present study aims to develop such pairings.Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models.Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (大柴胡湯), Dai-joki-To (大承気湯), Shigyaku-San (四逆散), Saiko-ka-ryukotsu-borei-To (柴胡加竜骨牡蛎湯), Keishi-bukuryo-Gan (桂枝茯苓丸), Hachimi-jio-Gan (八味地黄丸), Hange-shashin-To (半夏瀉心湯), Sho-saiko-To (小柴胡湯), Hochu-ekki-To (補中益気湯), Sho-kenchu-To (小建中湯), Toki-shakuyaku-San (当帰芍薬散), Ninjin-To (人参湯), and Dai-kenchu-To (大建中湯).Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education.

The objective of this review is to evaluate the anti-dementia activities of saffron and its combination with Kampo medicine. The Kampo formula Kamiuntanto composed of 13 crude drugs is well known for its anti-dementia activity. A significant increase in choline acetyltransferase activity and mRNA levels were observed. Polygala radix was identified as the most essential component drug in Kamiuntanto, probably due to the saponins, tenuifolin, and sinapinic acid. Ginseng was also identified as an essential Kamiuntanto component in terms of its synergistic functions with Polygala radix. Saffron, which was recommended in the Bencao Gangmu for memory and dementia, and is used as an anti-spasmodic, anti-catarrhal, and sedative herbal drug. Saffron and its major constituent, crocin were shown to enhance learning-memory, non-rapid eye movement (rem) sleep, and inhibit depression and neuronal cell death due to strong anti-oxidant and anti-inflammation activities. In addition based on the epidemiological studies such as the treatment of sleeping disorders and the clinical trials of saffron for Alzheimer patients, we demonstrated the indirect and direct anti-dementia activities of crocin and saffron. [ABSTRACT FROM AUTHOR]

The objective of this review is to evaluate the anti-dementia activities of saffron and its combination with Kampo medicine. The Kampo formula Kamiuntanto composed of 13 crude drugs is well known for its anti-dementia activity. A significant increase in choline acetyltransferase activity and mRNA levels were observed. Polygala radix was identified as the most essential component drug in Kamiuntanto, probably due to the saponins, tenuifolin, and sinapinic acid. Ginseng was also identified as an essential Kamiuntanto component in terms of its synergistic functions with Polygala radix. Saffron, which was recommended in the Bencao Gangmu for memory and dementia, and is used as an anti-spasmodic, anti-catarrhal, and sedative herbal drug. Saffron and its major constituent, crocin were shown to enhance learning-memory, non-rapid eye movement (rem) sleep, and inhibit depression and neuronal cell death due to strong anti-oxidant and anti-inflammation activities. In addition based on the epidemiological studies such as the treatment of sleeping disorders and the clinical trials of saffron for Alzheimer patients, we demonstrated the indirect and direct anti-dementia activities of crocin and saffron.

ObjectiveThe impact of the 2018 Japan Floods on prescriptions of Yokukansan was evaluated.MethodsThis was a retrospective cohort study based on the National Database of Health Insurance Claims which covers all the prescriptions issued in Japan. Participants were patients aged 65 or older who received any medical care at medical institutions located in the three most-severely affected prefectures between 1 year before and after the disaster. We analyzed the number of new prescriptions of Yokukansan and other Kampo drugs among those who had not been prescribed any Kampo for 1 year before the disaster. Kaplan-Meier analysis and a Cox proportional hazards model were used to evaluate the risk of the disaster for a new prescription.ResultsSubjects comprised 1,372,417 people (including 12,787 victims, 0.93%). The hazard ratio (HR) of the disaster for Yokukansan prescriptions was 1.49 [95% confidence intervals (CI): 1.25–1.78], and 1.54 (95% CI: 1.29–1.84) in the crude and age-sex adjusted model, respectively. The HR of the disaster for prescription of other Kampo drugs in the crude and adjusted model was 1.33 (95% CI: 1.27–1.39), and 1.32 (95% CI: 1.27–1.38), respectively. The magnitude of increase of victims prescribed Yokukansan (31.4%) was statistically higher than for those prescribed other Kampo drugs (19.3%) (p < 0.001).ConclusionThe disaster increased prescriptions of both Yokukansan and other Kampo drugs among elderly victims. The increase was more remarkable in Yokukansan than other Kampo drugs. Clinicians and policymakers should be aware of the increased need for Yokukansan in times of natural disaster.

BackgroundIn contrast to Western medicine which currently offers no approved pharmacotherapy options for cachexia, in Japan multi-component extracts of medicinal plants are used with coverage by the national health insurance. This so called “Kampo” medicine is an example of the modern concept of multi-component/multi-target therapy. For the three traditional preparations Hochuekkito (補中益気湯), Juzentaihoto (十全大補湯), and Rikkunshito (六君子湯), a multitude of clinical research data relating to cachexia has been published. These preparations are also referred to as “Hozai” (補剤). A similar concept is found in Russian herbal medicine, where the term “Adaptogen” was coined for pharmacologically active substances which enhance adaptive stress repose.MethodsScientific literature—including original Japanese articles—was reviewed regarding the effects of these herbal preparations on cachexia. Cachexia is a complex set of symptoms including muscle atrophy with loss of weight, fatigue, and weakness.ResultsIn a 1985 study by Kuroda et al., Hochuekkito showed efficacy in involuntary weight loss and fatigue in 63% of 162 patients with genitourinary cancer. For cancer-related fatigue, a significant improvement was reported within 2 weeks by Jeong et al. in 2010. In patients with chronic fatigue syndrome, Hochuekkito showed an overall improvement with 8–12 weeks of therapy in a 1997 study by Kuratsune et al. In a 2005 randomized placebo-controlled trial by Satoh et al. on 13 geriatric Q1 patients in a 16-week treatment protocol, Hochuekkito showed significant improvement of general health, physical functioning and the Profile of Mood States (POMS). In 71 geriatric COPD patients in a 2009 placebo-controlled randomized study, Tatsumi et al. found a significant body weight increase and a CRP, TNF-α, IL-6 decrease over 6 months of therapy. For Juzentaihoto in 48 hepatocellular carcinoma patients, Tsuchiya et al. 2008 documented a significantly longer recurrence-free survival (49 vs. 24 months) as compared to the control group (p=0.023). For the much simpler Rikkunshito prescription, a 2011 retrospective study by Fujitsuka et al. on 39 Stage III/IV pancreatic cancer patients treated with Gemcitabine (n=33) or Gemcitabine/Rikkunshito (n=6) showed a significantly prolonged median survival with 224 vs. 378.5 days (p < 0.05). In a 2011 open-label clinical study by Utumi et al. on geriatric cachexia in 6 dementia patients, treatment with Rikkunshito for 4 weeks resulted in a significant body weight increase. In all the above studies, the standardized dosage of 3x2.5 g/d extract granules for most Japanese health insurance-covered Kampo extract-preparations was applied.ConclusionAs there is currently no accepted pharmacotherapy option for cachexia available in the West, a transfer of these East Asian gold standard prescriptions into the European market would be desirable. We were further able to demonstrate that the mTOR, interleucin, and melatonin pathways are modified by herbal compounds which thus counteract cachexia. More research in this field is urgently needed in order to provide new, effective treatments for cachexia patients.

Background: In contrast to Western medicine which currently offers no approved pharmacotherapy options for cachexia, in Japan multi-component extracts of medicinal plants are used with coverage by the national health insurance. This so called "Kampo" medicine is an example of the modern concept of multi-component/multi-target therapy. For the three traditional preparations Hochuekkito (補中益気湯), Juzentaihoto (十全大補湯), and Rikkunshito (六君子湯), a multitude of clinical research data relating to cachexia has been published. These preparations are also referred to as "Hozai" (補剤). A similar concept is found in Russian herbal medicine, where the term "Adaptogen" was coined for pharmacologically active substances which enhance adaptive stress repose. Methods: Scientific literature—including original Japanese articles—was reviewed regarding the effects of these herbal preparations on cachexia. Cachexia is a complex set of symptoms including muscle atrophy with loss of weight, fatigue, and weakness. Results: In a 1985 study by Kuroda et al., Hochuekkito showed efficacy in involuntary weight loss and fatigue in 63% of 162 patients with genitourinary cancer. For cancer-related fatigue, a significant improvement was reported within 2 weeks by Jeong et al. in 2010. In patients with chronic fatigue syndrome, Hochuekkito showed an overall improvement with 8–12 weeks of therapy in a 1997 study by Kuratsune et al. In a 2005 randomized placebo-controlled trial by Satoh et al. on 13 geriatric Q1 patients in a 16-week treatment protocol, Hochuekkito showed significant improvement of general health, physical functioning and the Profile of Mood States (POMS). In 71 geriatric COPD patients in a 2009 placebo-controlled randomized study, Tatsumi et al. found a significant body weight increase and a CRP, TNF-α, IL-6 decrease over 6 months of therapy. For Juzentaihoto in 48 hepatocellular carcinoma patients, Tsuchiya et al. 2008 documented a significantly longer recurrence-free survival (49 vs. 24 months) as compared to the control group (p=0.023). For the much simpler Rikkunshito prescription, a 2011 retrospective study by Fujitsuka et al. on 39 Stage III/IV pancreatic cancer patients treated with Gemcitabine (n=33) or Gemcitabine/Rikkunshito (n=6) showed a significantly prolonged median survival with 224 vs. 378.5 days (p < 0.05). In a 2011 open-label clinical study by Utumi et al. on geriatric cachexia in 6 dementia patients, treatment with Rikkunshito for 4 weeks resulted in a significant body weight increase. In all the above studies, the standardized dosage of 3x2.5 g/d extract granules for most Japanese health insurance-covered Kampo extract-preparations was applied. Conclusion: As there is currently no accepted pharmacotherapy option for cachexia available in the West, a transfer of these East Asian gold standard prescriptions into the European market would be desirable. We were further able to demonstrate that the mTOR, interleucin, and melatonin pathways are modified by herbal compounds which thus counteract cachexia. More research in this field is urgently needed in order to provide new, effective treatments for cachexia patients. [ABSTRACT FROM AUTHOR]

Ninjinyoeito, Hochuekkito, and Juzentaihoto are the three types of Kampo-hozai used to support the treatment of various diseases by energizing patients through improved mental health. While Kampo-hozais are clinically used to improve mental energy decline, a comparison between their effects on neuropsychiatric symptoms like anxiety and sociability and the strength of their effects has not been conducted. Therefore, this study compared the effects of Ninjinyoeito, Hochuekkito, and Juzentaihoto on psychiatric symptoms using neuropeptide Y knockout (NPY-KO) zebrafish, a suitable animal model for anxiety and low sociability. Neuropeptide Y knockout zebrafish were fed a Ninjinyoeito, Hochuekkito, or Juzentaihoto-supplemented diet for 4 days. Then, sociability was analyzed using a three-Chambers test and anxiety-like behavior was evaluated using the cold stress and novel tank tests. The results showed that Ninjinyoeito treatment improved the low sociability of neuropeptide Y knockout, while Hochuekkito and Juzentaihoto did not. Neuropeptide Y knockout exhibited anxiety-like behaviors, such as freezing and swimming in the wall area under cold stress, but Ninjinyoeito treatment improved these behaviors. However, these anxiety-like behaviors were not improved by Hochuekkito and Juzentaihoto. Ninjinyoeito treatment also improved anxiety-like behaviors of neuropeptide Y knockout in the novel tank test. However, no improvement was shown in the Hochuekkito and Juzentaihoto groups. This trend was also confirmed in the low water stress test using wild-type zebrafish. This study exhibits that among the three types of Kampo-hozai, Ninjinyoeito is the most effective in psychiatric disorders associated with anxiety and low sociability., Competing Interests: Author RT was employed by Kracie Pharma, Ltd., Pharmacological Department of herbal medicine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kawabe, Nishida, Takahashi, Inui and Shiozaki.)

Objective: The impact of the 2018 Japan Floods on prescriptions of Yokukansan was evaluated., Methods: This was a retrospective cohort study based on the National Database of Health Insurance Claims which covers all the prescriptions issued in Japan. Participants were patients aged 65 or older who received any medical care at medical institutions located in the three most-severely affected prefectures between 1 year before and after the disaster. We analyzed the number of new prescriptions of Yokukansan and other Kampo drugs among those who had not been prescribed any Kampo for 1 year before the disaster. Kaplan-Meier analysis and a Cox proportional hazards model were used to evaluate the risk of the disaster for a new prescription., Results: Subjects comprised 1,372,417 people (including 12,787 victims, 0.93%). The hazard ratio (HR) of the disaster for Yokukansan prescriptions was 1.49 [95% confidence intervals (CI): 1.25-1.78], and 1.54 (95% CI: 1.29-1.84) in the crude and age-sex adjusted model, respectively. The HR of the disaster for prescription of other Kampo drugs in the crude and adjusted model was 1.33 (95% CI: 1.27-1.39), and 1.32 (95% CI: 1.27-1.38), respectively. The magnitude of increase of victims prescribed Yokukansan (31.4%) was statistically higher than for those prescribed other Kampo drugs (19.3%) ( p < 0.001)., Conclusion: The disaster increased prescriptions of both Yokukansan and other Kampo drugs among elderly victims. The increase was more remarkable in Yokukansan than other Kampo drugs. Clinicians and policymakers should be aware of the increased need for Yokukansan in times of natural disaster., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ishida, Yoshida, Kashima, Okazaki and Matsumoto.)