研究者詳細 - 吉野　鉄大

論文 - 吉野　鉄大

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Conference report: Fifth annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Tanide S., Hamai M., Nishiura R., Hatae A., Nose I., Oda Y., Fukada Y., Yang X., Ando H., Ogawa K., Murakami K., Nakashima S.

Traditional and Kampo Medicine 12 （ 1 ） 74 - 79 2025年04月

Seven young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the Fifth Annual Young Researcher Forum held the day before the 2024 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Ms Tanide presented on the changes in flavonoid and synephrine content in chimpi based on the storage period. Ms Hamai discussed natural compounds that contribute to improving bortezomib resistance in myeloma cells and their mechanisms of action. Ms Nishiura presented the production of a monoclonal antibody against geniposide and its application in indirect competitive enzyme-linked immunosorbent assay. Mr Hatae presented about the effects of ninjin'yoeito on cisplatin-induced anorexia and the variations in intestinal clock genes. Ms Nose explored the analgesic effects of bushi-containing Kampo formulas, with a focus on goshajinkigan's improvement of cold allodynia. Dr Oda discussed the antifungal activity of henna leaves against Malassezia. Lastly, Mr Fukuda presented how cultivation environments affect the quality of Schizonepeta spikes, including their morphology and component content. The event, conducted both in person and online, attracted a total of 54 participants. Looking ahead, we aim to further develop and continue hosting this forum in 2025 and beyond, fostering the advancement of research in this field.

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Survey of attitudes toward clinical research among Japanese traditional (Kampo) medicine specialists and certified doctors affiliated with the Japan Society for Oriental Medicine

Nogami T., Uneda K., Yoshino T., Ito H., Imoto S., Tahara E., Sunagawa M., Takayama S., Yakubo S., Mitani K.

Traditional and Kampo Medicine 12 （ 1 ） 27 - 37 2025年04月

Aim: This study aims to assess the motivation, capability, and working environment of Japanese traditional (Kampo) medicine (JTM) specialists and certified physicians affiliated with the Japan Society for Oriental Medicine regarding clinical research. Their awareness and perception of COVID-19 studies and their interest in clinical research based on traditional JTM diagnostic concepts are explored. Methods: An online survey was conducted between May 20 and June 30, 2024, using Google Forms, targeting 2146 Japan Society for Oriental Medicine-certified JTM specialists and physicians. The survey covered their awareness of and participation in COVID-19 research, barriers to research, and educational needs for clinical researcher training. Results: In total, 570 participants (26.6%) responded, 44.1% of whom had more than 15 years of certification experience. Approximately 50% were unaware of the COVID-19 studies, and participation rates were low. The most common barriers to conducting clinical research included lack of time (58.1%), funding (54.8%), and research personnel (51.1%). In terms of educational needs, 74.3% of respondents expressed a need for statistical analysis training, and nearly 90% felt clinical research education should occur within 10 years of obtaining their medical licenses. Conclusion: This study reveals gaps in awareness and participation in clinical research among JTM specialists. Many respondents expressed willingness to engage in research; however, barriers such as limited time, funding, and personnel remain critical challenges. Furthermore, the need for specialized educational programs was strongly emphasized. Addressing these issues is essential for promoting clinical research in JTM.

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A Simulated Interprofessional Team Conference Using Cross-Training for Junior Healthcare Students in Interprofessional Education: a Qualitative Content Analysis

Tomisaki E., Haruta J., Horiguchi T., Arahata T., Fukui R., Uno S., Ando T., Yoshino T., Ishikawa S., Suzuki S., Yamaura K., Monkawa T.

Advances in Medical Education and Practice 16 583 - 594 2025年

ISSN 1179-7258

Purpose: In 2021, we introduced a new simulation-based learning program focusing on a roleplay conference before patient discharge. This study aimed to evaluate the program’s effectiveness and highlight the significance of cross-training in interprofessional education (IPE). Methods: In September 2023, the program included 346 students (98 medical, 110 nursing, and 138 pharmacy students). The students’ reflective writing was analyzed using inductive content analysis to describe their learning and perspectives. The original items, subcategories, and main categories were extracted. The simulation involved the students role-playing various healthcare professionals during a discharge-planning conference for a stroke patient. This allowed them to experience the challenges and dynamics of interprofessional collaboration. Results: Student feedback emphasized the importance of understanding what constitutes a good healthcare team. A total of 203 items were grouped into eight main categories and 17 subcategories, including patient-centered care (related to the importance of patient-centered care, supporting patient decision-making, communicating with patients during conferences, and facilitating decision-making processes), contrasts in patient and interprofessional communication, conference communication (challenge of building consensus, the way to proceed conferences, importance of conference preparation, and process of information aggregation and realization of outcomes), mutual recognition and role contribution, building relationships (importance of daily interprofessional communication), understanding one’s profession (reflection on one’s own profession, understanding the roles of different professions, and communication within one’s own professional context), recursion into learning (motivation for continuous learning and improvement), and understanding other professions (understanding the role and perspectives of other professions and recognizing professional differences). Specific feedback highlighted improved empathy and communication skills. Students recognized the value of each profession’s contribution to patient care. Moreover, students reported a deeper appreciation of patient-centered approaches and the complexities of coordinating care across different healthcare roles. Conclusion: Simulated interprofessional team conferences using cross-training effectively taught junior students to understand the essence of a good healthcare team and the importance of a patient-centered approach. Cross-training significantly enhanced students’ interprofessional competencies, communication skills, and empathy toward other professions. This case underscores the necessity of incorporating cross-training into IPE to prepare healthcare professionals for collaborative practice and improve patient outcomes. Future research should consider expanding the scope to include more diverse scenarios and longitudinal assessments to measure longterm impacts on professional practice.

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Three Kampo medicines—bofutsushosan, boiogito, and daisaikoto—have different effects on host fat accumulation and the intestinal microbiota in a high-fat-diet–induced mouse model of obesity

Nakamichi K., Yoshino T., Akiyama M., Jibiki A., Yokoyama Y., Kawazoe H., Suzuki S., Watanabe K., Kim Y.G., Nakamura T.

Journal of Natural Medicines 2025年

ISSN 13403443

Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, Clostridium sensu stricto 1, Erysipelatoclostridium, Roseburia, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.

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3-epi-18b-Glycyrrhetinic Acid or Its Glucuronide, the Metabolites of Glycyrrhizinic Acid with Individual Differences, Correlated with Diagnostic Marker for Licorice-Induced Pseudoaldosteronism in Humans

Sakoda R., Ishiuchi K., Yoshino T., Tsunoo Y., Namiki T., Ogawa-Ochiai K., Minamizawa K., Fukunaga K., Watanabe K., Makino T.

Drug Metabolism and Disposition 52 （ 12 ） 1407 - 1416 2024年12月

査読有り, ISSN 00909556

Licorice is a crude drug that is used in traditional Japanese Kampo medicine and is also used as a sweetener. Occasionally, it causes pseudoaldosteronism (PsA) as a side effect. The major symptoms include hypokalemia, hypertension, edema, and low plasma aldosterone levels. PsA might be caused by the metabolites of glycyrrhizinic acid (GL), a component of licorice. The development of PsA markedly varies among individuals; however, the factors that cause these individual differences remain unknown. In this study, 78 patients who consumed Kampo medicines containing licorice were enrolled, and their laboratory data, including serum potassium levels, plasma aldosterone concentrations (PAC), and the concentrations of GL metabolites in the residual blood and/or urine samples were evaluated. Of the 78 participants, 18b-glycyrrhetinic acid (GA), 3-epi-GA, 3-oxo-GA, 18b-glycyrrhetinyl-30-O-glucuronide (GA30G), and 3-epi-GA30G were detected in the serum samples of 65, 47, 63, 62, and three participants, respectively. Of the 29 urine samples collected, GA30G and 3-epi-GA30G were detected in 27 and 19 samples. 3-epi-GA30G is a newly found GL metabolite. Moreover, 3-epi-GA, 3-oxo-GA, and 3-epi-GA30G were identified in human samples for the first time. High individual differences were found in the appearances of 3-epi-GA in serum and 3-epi-GA30G in urine, and the concentrations of these metabolites were correlated with serum PsA markers. The inhibitory titers of 3-epi-GA, 3-oxo-GA, GA30G, and 3-epi-GA30G on human 11b-hydroxysteroid dehydrogenase type 2 were almost similar. These findings suggest that 3-epi-GA and/or 3-epi-GA30G are associated with individual differences in the development of PsA.

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Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden

Wu X., Yoshino T., Maeda-Minami A., Ishida S., Tanaka M., Nishi A., Tahara Y., Inami R., Sugiyama A., Horiba Y., Watanabe K., Mimura M.

Scientific Reports 14 （ 1 ） 1918 2024年12月

Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20–59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10<sup>–5</sup>) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity.

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Current situation and future issues with Kampo medicine: A survey of Japanese physicians

Uneda K., Yoshino T., Ito H., Imoto S., Nogami T.

Traditional and Kampo Medicine 11 （ 2 ） 156 - 166 2024年08月

Aim: We aimed to elucidate the present clinical situation, future challenges, and potential need for diagnostic support software in Kampo medicine. Methods: We conducted an online survey (comprising 28 questions) of Japanese physicians from the 23 to 24 January 2024 via MedPeer. The participants' responses were stratified according to their age distribution. Results: We evaluated data for 652 respondents. The most common respondent age groups were those in their 30s and 40s. The most common specialty of respondents was internal medicine (43.7%). Only 33.7% of respondents had received education on Kampo medicine at university. Most respondents (90.0%) were not licensed as certified physicians or members of the Japan Society for Oriental Medicine. Most respondents (86.7%) currently prescribed Kampo formulas (current users); only 3.8% had no experience in prescribing Kampo formulas. The conditions for which Kampo formulas were frequently prescribed were muscle cramps, constipation, medically unexplained symptoms/menopausal syndrome, appetite loss/malnutrition, and fatigue. However, 48.3% of current users did not use traditional Kampo patterns (sho). The most frequent issues reported by respondents were the lack of scientific evidence and standardization of diagnostic methods in Kampo medicine. Respondents indicated the need for postgraduate education and implementation of diagnostic support software for using Kampo patterns by non-specialists in Kampo medicine. Conclusion: There was a discrepancy between the high frequency of Kampo formula prescriptions and the low use of traditional Kampo patterns in Japan. Diagnostic support software is likely to become a useful method of improving appropriate Kampo formula prescriptions by non-specialists.

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Discrepancies of frequent symptoms in licorice-induced pseudoaldosteronism: A comparison of a systematic case review and the Ministry of Health, Labour and Welfare's manual

Hattori Y., Asano Y., Yoshino T.

Traditional and Kampo Medicine 11 （ 2 ） 167 - 169 2024年08月

Background: Licorice-induced pseudoaldosteronism has been identified as a side effect of excessive licorice consumption. This condition is often characterized by hypertension, hypokalemia, and hyporeninemic hypoaldosteronism. If left untreated, this condition can lead to severe complications, such as arrhythmia and rhabdomyolysis, which can be life-threatening. Thus, it is critical to recognize the early symptoms of pseudoaldosteronism to facilitate prompt intervention and effective management. Here, we investigated the frequency of various accompanying symptoms by systematically reviewing case reports of licorice-induced pseudoaldosteronism not covered in similar studies and comparing findings with the manual on pseudoaldosteronism published by the Ministry of Health, Labour and Welfare (MHLW). Methods: A comprehensive search was conducted using MEDLINE/PubMed to gather relevant human studies published between 1960 and July 2023 and written in English; data focusing on accompanying symptoms were summarized. Results: Thirty-seven pertinent articles, encompassing 48 case reports (26 females and 1 unreported sex, mean age 64.6 ± 14.6), were identified and scrutinized. The analysis revealed that hypertension was the most prevalent followed by weakness and edema. None of the researched cases reported instances of spasticity or rigidity. Discussion: The study findings identified hypertension and weakness followed by edema as the predominant symptoms associated with pseudoaldosteronism which is in agreement with the MHLW manual. However, we doubt that spasticity, rigidity, and possibly numbness could be noticed by patients and their families as common initial symptoms outlined in the manual.

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Conference report: Fourth annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Sakoda R., Nishihara M., Okayama M., Muraoka T., Yang X., Ando H., Nakashima S.

Traditional and Kampo Medicine 11 （ 1 ） 83 - 85 2024年04月

Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the Fourth Annual Young Researcher Forum held the day before the 2023 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Mr Sakoda outlined his research plan, emphasizing the potential of yokukansan to enhance palliative care for cancer patients. Meanwhile, Ms Tanide and Mr Nishihara explored the correlation among component contents in Coptis japonica on Sado Island. Additionally, Mr Okayama presented his study, focusing on the use of Sinomenium acutum-derived compounds to inhibit the Wnt/β-catenin pathway and eradicate cancer stem cells. Finally, Mr Muraoka shared insights from his research on the inhibitory properties of Cassia obtusifolia sprout components. The event, conducted both in person and online, attracted a total of 58 participants. Looking ahead, we aim to further develop and continue hosting this forum in 2024 and beyond, fostering the advancement of research in this field.

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Machine learning model for predicting the cold–heat pattern in Kampo medicine: a multicenter prospective observational study

Maeda-Minami A., Yoshino T., Katayama K., Horiba Y., Hikiami H., Shimada Y., Namiki T., Tahara E., Minamizawa K., Muramatsu S.I., Yamaguchi R., Imoto S., Miyano S., Mima H., Uneda K., Nogami T., Fukunaga K., Watanabe K.

Frontiers in Pharmacology 15 1412593 - 1412593 2024年

ISSN 1663-9812

Objective: The purpose of this study was to predict the four cold–heat patterns in patients who have the subjective symptoms of the cold–heat pattern described in the International Classification of Diseases Traditional Medicine Conditions – Module 1 by applying a machine learning algorithm. Methods: Subjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern. Results: We included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold–heat pattern. Conclusion: We developed a prediction model on cold–heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold–heat pattern diagnosis by the physician.

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Patient prognosis and prediction model for taking Kampo formulas in dysmenorrhea: An observational study

Maeda-Minami A., Kawamoto A., Yoshino T., Yokoyama Y., Suzuki S., Horiba Y., Nakamura T., Mimura M., Watanabe K.

Medicine United States 102 （ 48 ） e36191 2023年12月

ISSN 00257974

Two representative Kampo formulas, keishibukuryogan and tokishakuyakusan, are frequently prescribed for patients with dysmenorrhea. We previously constructed a model that could predict which of these 2 formulas was most suitable, which is based on 4 subjective symptoms and 3 objective signs. To evaluate the prognosis of patients with dysmenorrhea using the established prediction model and assess the treatment outcomes between those treated in accordance with the prediction model and those who received various other treatments. In this retrospective, observational study, we included patients with menstrual pain who visited the Kampo Clinic at the Keio University Hospital for the first time between October 2014 and December 2020. These patients were monitored over a 90-day follow-up period. Participants were categorized into 2 groups: model-accordance and various-options. The progression of visual analogue scale (VAS) values was evaluated by determining the slopes from regression analysis between these 2 groups, with changes corroborated by the medical records. The study comprised 57 patients: 37 in the model-accordance group and 20 in the various-options group. Notably, the various-options group reported a significantly higher number of subjective symptoms (P = .03). The VAS value showed a decline, as indicated by the negative slope value of the regression line, across both groups - irrespective of their classification. There were no significant differences in the occurrence of adverse events between the 2 groups. The prognosis of patients with dysmenorrhea and the incidence of adverse events remained consistent, regardless of whether the treatment approach was in accordance with the prediction model or varied. Further studies are warranted to assess the prognosis when Kampo formulas are chosen based on the prediction model in the various-options population.

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A review of frequently used Kampo prescriptions. Part 3. Yokukansan

Yamaguchi H., Yoshino T., Oizumi H., Arita R., Nogami T., Takayama S.

Traditional and Kampo Medicine 10 （ 3 ） 197 - 223 2023年12月

Background: The source of yokukansan (YKS) is thought to be Baoying-Jinjiang (Hoeikinkyōroku in Japanese) by Xue Ji. YKS was originally designed for children and indicated for spasms, clenching of teeth, digestive dysfunction due to mental instability, and insomnia. Key Findings: YKS formula consists of seven types of crude drugs. Clinical studies have revealed that YKS exerts physiological effects including the treatment of behavioral and psychiatric symptoms of dementia (BPSD), preoperative sedation and anxiety, and postoperative delirium. A meta-analysis showed that YKS could improve BPSD and daily living activities; however, no improvement in cognitive function was observed. Preclinical studies have also reported that YKS modulates neuronal pathways in the central nervous system, including the serotonergic, glutamatergic, GABAergic, and other neurotransmitter pathways. The incidence of adverse events associated with YKS was 5.17%, with the major adverse effect being pseudoaldosteronism. Routine blood sampling is considered for hypokalemia prevention. Conclusion: YKS is useful for BPSD and perioperative mental instability. The modulation of the serotonergic and glutamatergic neural pathways is one of mechanisms. Pseudoaldosteronism is one of the side effects.

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Development of a novel drug information provision system for Kampo medicine using natural language processing technology

Maeda-Minami A., Yoshino T., Yumoto T., Sato K., Sagara A., Inaba K., Kominato H., Kimura T., Takishita T., Watanabe G., Nakamura T., Mano Y., Horiba Y., Watanabe K., Kamei J.

BMC Medical Informatics and Decision Making 23 （ 1 ） 119 2023年12月

Background: Kampo medicine is widely used in Japan; however, most physicians and pharmacists have insufficient knowledge and experience in it. Although a chatbot-style system using machine learning and natural language processing has been used in some clinical settings and proven useful, the system developed specifically for the Japanese language using this method has not been validated by research. The purpose of this study is to develop a novel drug information provision system for Kampo medicines using a natural language classifier® (NLC®) based on IBM Watson. Methods: The target Kampo formulas were 33 formulas listed in the 17th revision of the Japanese Pharmacopoeia. The information included in the system comes from the package inserts of Kampo medicines, Manuals for Management of Individual Serious Adverse Drug Reactions, and data on off-label usage. The system developed in this study classifies questions about the drug information of Kampo formulas input by natural language into preset questions and outputs preset answers for the questions. The system uses morphological analysis, synonym conversion by thesaurus, and NLC®. We fine-tuned the information registered into NLC® and increased the thesaurus. To validate the system, 900 validation questions were provided by six pharmacists who were classified into high or low levels of knowledge and experience of Kampo medicines and three pharmacy students. Results: The precision, recall, and F-measure of the system performance were 0.986, 0.915, and 0.949, respectively. The results were stable even with differences in the amount of expertise of the question authors. Conclusions: We developed a system using natural language classification that can give appropriate answers to most of the validation questions.

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Contribution of traditional Japanese Kampo medicines, kakkonto with shosaikotokakikyosekko, in treating patients with mild-to-moderate coronavirus disease 2019: Further analysis of a multicenter, randomized controlled trial

Takayama S., Namiki T., Arita R., Ono R., Kikuchi A., Ohsawa M., Saito N., Suzuki S., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Takagi A., Yamaguchi T., Ishii T., Hisanaga A., Mitani K., Ito T.

Journal of Infection and Chemotherapy 29 （ 11 ） 1054 - 1060 2023年11月

ISSN 1341321X

We previously reported the finding of symptom relief in a randomized controlled trial with the combined use of kakkonto and shosaikotokakikyosekko added to conventional treatment in patients with coronavirus disease 2019 (COVID-19). For further evaluation, we performed post hoc analysis focused on symptom disappearance without recurrence, to determine a clearer effect of Kampo medicine. Patients with mild and moderate COVID-19 were randomly allocated to a control group receiving symptomatic therapy or a Kampo group receiving kakkonto (2.5 g) with shosaikotokakikyosekko (2.5 g) three times daily in addition to symptomatic therapy. The data of 161 patients (Kampo group, n = 81; control group, n = 80) were analyzed post hoc for the time to symptom disappearance. Kaplan-Meier and Cox proportional hazard estimates of disappearance of symptoms showed that all and each symptom targeted in this study disappeared faster in the Kampo group than in the control group, although not statistically significant (all symptomatic cases; hazard ratio [HR] 3.73, 95% confidence interval [CI] 0.46−29.98, log-rank p = 0.1763). In a supplemental assessment using covariate adjustment and competing risk analysis, fever disappeared faster in the Kampo group than in the control group (all symptomatic cases, HR 1.62, 95% CI 0.99−2.64, p = 0.0557; unvaccinated cases, HR 1.68, 95% CI 1.00−2.83, p = 0.0498) and shortness of breath disappeared significantly faster in Kampo group than in control group (all symptomatic cases, HR 1.92, 95% CI 1.07−3.42, p = 0.0278; unvaccinated cases, HR 2.15, 95% CI 1.17−3.96, p = 0.0141). These results demonstrate the advantages of Kampo treatment for acute COVID-19.

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The Integration of Traditional Medicine with Conventional Biomedicine: A Narrative Review of the Japanese Perspective

Yoshino T., Kashio A., Terasawa Y., Hachiki M., Yoshinaga R., Arita R.

Journal of Integrative and Complementary Medicine 29 （ 6-7 ） 372 - 379 2023年07月

ISSN 27683605

Objectives: This is a narrative review of the integration of traditional medicine with conventional biomedicine in present day Japan, whose aging population is considered one of the largest globally. Design: It is focused on the aging population because this age group most avails of healthcare. We also tried to describe the unique Japanese medical situations, clinical outcome of Japanese traditional medicine (Kampo medicine) which may include acupuncture, and education of Kampo medicine workforce. Results: Conventional schools of medicine in Japan are required to teach Kampo medicine, and most Japanese physicians (>80%) prescribe traditional medicine, especially in primary care settings. The universal national healthcare system covers Kampo medicine prescribed by physicians and treatment by acupuncturists (they sometimes refer patients who may need evaluation by physicians), enhancing access to primary healthcare. Additionally, pharmacists who graduated from conventional schools of pharmacy also select and sell Kampo medicine as over-the-counter (OTC) medication. Kampo medicine available as prescription drugs and OTC is effective, and has been proven to be economically beneficial in several clinical settings. Conclusions: An aging population is a global concern for both developed and developing countries. Japan, having a significantly-large aging population, integrates conventional biomedicine and traditional medicine in its universal national healthcare coverage, through its biomedically-trained physicians and pharmacists who also learned traditional medicine, as well as the acupuncturists. By reviewing the current situation in Japan, the authors hope to introduce the future of the global contribution of traditional, complementary, and integrative medicine in primary care.

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Conference report: Third annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Yokogawa T., Nakamichi K., Manse Y., Yoshikawa H., Sasaki H., Ando H., Nakashima S.

Traditional and Kampo Medicine 10 （ 1 ） 78 - 81 2023年04月

Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the third annual young researcher forum entitled “Respecting and Breaking Traditions,” held 1 week before the 2022 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Dr. Yokogawa presented her research focusing on the mechanism of the Ayurveda drug-eluting string, Kshara Sutra, in treating anal fistulas, reporting on its effects on the anal tissue in an anal fistula rat model and its antibacterial activity against Escherichia coli and Staphylococcus aureus, the causative organisms of anal fistulas. Mr. Nakamichi presented his research focusing on the relationship between the efficacy of Kampo medicines with anti-obesity effects and intestinal microbiota composition. His results partially revealed that bofutsushosan and boiogito affect lipid metabolism in mice and correlate with the intestinal microbiota composition. Dr. Manse reported the anti-inflammatory activity of diterpenoid components in Enmei-so (Isodonis Herba), revealing its novel inhibitory activity on nitric oxide released from activated macrophages and on inflammatory cytokines, and identified active components contributing to the inhibition and the mechanism of action. Mr. Yoshikawa reported the anticancer activity of small molecular compounds isolated from the medicinal plants, Valeriana fauriei and Hypericum erectum. His results suggest that five compounds may increase the sensitivity of human cervical carcinoma cells to adriamycin via HSP105 expression suppression. The event was conducted online, and included 78 participants. We intend to hold and improve this forum in 2023 and the future.

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To whom the side effect of licorice, pseudoaldosteroneism, will occur: case-control study.

Tetsuhiro Yoshino, Komatsu, Akihiro, Nakamura, Tomonori and Watanabe, Kenji

2023年03月

Background: Pseudoaldosteronism is a well-known side effect of licorice or glycyrrhizin (GL), one of major components in licorice. Pseudoaldosteronism mimics primary aldosteronism which causes hypokalemia, hypertension, and extremities’ edema. GL can be used to treat chronic hepatitis, but also plays important role in pseudoaldosteronism. The importance of multidrug resistance protein 2 (Mrp2) in GL excretion has been reported recently. Dysfunction of Mrp2 causes elevated direct bilirubin (DB), GL, and its metabolites. Hence, elevated DB can be a risk predictor of pseudoaldosteronism. The relationship between pseudoaldosteronism and elevated DB, however, has not been studied as yet. Objectives: To evaluate the relationship between elevated DB and hypokalemia, the most sensitive marker of pseudoaldosteronism.

Sigmoid Volvulus

Yoshino T., Hiruma H.

Annals of Internal Medicine Clinical Cases 2 （ 12 ） 2023年

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Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation)

Takayama S., Yoshino T., Koizumi S., Irie Y., Suzuki T., Fujii S., Katori R., Kainuma M., Kobayashi S., Nogami T., Yokota K., Yamazaki M., Minakawa S., Chiba S., Suda N., Nakada Y., Ishige T., Maehara H., Tanaka Y., Nagase M., Kashio A., Komatsu K., Nojiri M., Shimooki O., Nakamoto K., Arita R., Ono R., Saito N., Kikuchi A., Ohsawa M., Nakae H., Mitsuma T., Mimura M., Ishii T., Nochioka K., Chiu S.W., Yamaguchi T., Namiki T., Hisanaga A., Mitani K., Ito T.

Internal Medicine 62 （ 2 ） 187 - 199 2023年

ISSN 09182918

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

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Multicenter, randomized controlled trial of traditional Japanese medicine, kakkonto with shosaikotokakikyosekko, for mild and moderate coronavirus disease patients

Takayama S., Namiki T., Arita R., Ono R., Kikuchi A., Ohsawa M., Saito N., Suzuki S., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Nochioka K., Takagi A., Mimura M., Yamaguchi T., Ishii T., Hisanaga A., Mitani K., Ito T.

Frontiers in Pharmacology 13 1008946 2022年11月

ISSN 1663-9812

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom’s relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan–Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03–3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference −0.13, 95% CI −0.27–0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients. Clinical Trial Registration: https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020]

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吉野 鉄大

論文 - 吉野 鉄大

吉野　鉄大

論文 - 吉野　鉄大