Pharmacological characteristics of Kampo medicine as a mixture of constituents and ingredients

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto （Shao-Yao-Gan-Cao-Tang） as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito （Mu-Fang-Ji-Tang） inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine （a main ingredient of Mokuboito） as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan （Diao-Teng-San） caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan （Liu-Wei-Wan）, Hachimijiogan （Ba-Wei-Di-Huang-Wan） and Goshajinkigan （Niu- Che-Shen-Qi-Wan） increase in order the number of contained ingredients. The formulations with more herbs （ingredients） produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine （mixture） are never just a sum of each effect induced by a lot of in qredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.

Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness:A retrospective pilot study

BACKGROUND Persistent postural-perceptual dizziness(PPPD)is a functional disorder,typically preceded by acute vestibular disorders.It is characterized by a shift in processing spatial orientation information,to favor visual over vestibular and somatosensory inputs,and a failure of higher cortical mechanisms.To date,no therapies for PPPD have been approved.Kampo medicine hangebyakujutsutemmato(HBT)has been reported to alleviate disturbances of equilibrium.We hypothesized that HBT would be a beneficial treatment for PPPD.AIM To examine the efficacy of HBT for the treatment of PPPD.METHODS Patients with PPPD were enrolled and divided into two groups:The HBT group(n=24)and the non-HBT group(n=14).The participants completed questionnaire surveys[Niigata PPPD questionnaire(NPQ),dizziness handicap inventory,hospital anxiety and depression scale(HADS),orthostatic dysregulation questionnaire,pittsburg sleep quality index(PSQI),and motion sickness scores]before and after HBT treatment.Additionally,to identify HBT responders,multivariate regression analysis was performed using the results of the ques-tionnaire surveys and equilibrium tests;including stabilometry,and caloric,vestibular evoked myogenic response,and head-up tilt tests.RESULTS Thirty-eight outpatients were included in this study,of which 14 patients(3 men,11 women;mean age,63.5±15.9 years)received treatment without HBT,and 24(1 man,23 women;mean age,58.2±18.7 years)received combination treatment with HBT.Following HBT treatment,NPQ scores decreased significantly(baseline 40.1±10.0 vs 2 mo 24.6±17.7,P<0.001).No statistically significant changes were observed in the NPQ scores in the non-HBT group(baseline 38.6±12.2 vs 2 mo 39.4±14.4,P=0.92).Multivariable regression analysis revealed that the results of stabilometry(P=0.02)and the caloric(P=0.03),and head-up tilt tests(P<0.001),HADS(P=0.003),and PSQI(P=0.01)were associated with HBT responsiveness in PPPD patients.CONCLUSION HBT may be an effective adjunct therapy for PPPD.Patients with autonomic dysfunction,unstable balance,semicircular canal paresis,anxiety,and poor sleep quality may be high responders to HBT.

Long-term administration of traditional kampo medicine shimotsuto, juzentaihoto and unseiin inhibits experimental thrombosis in mice

Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in arterial thrombotic conditions. The present study aimed to assess the antithrombotic effect of three Kampo, using well-established in vitro and animal models of thrombosis. Western-style highfat diet containing 1% Kampo (Shimotsuto, Juzentaihoto or Unseiin) was administered to C57BL/6 mice for 12 weeks. The effect on thrombus formation by laser irradiation of the carotid artery of mice was assessed. In addition the ex-vivo technique of shear-induced platelet reactivity measurement (haemostatometry) and the in vivo test of endothelial function (flowmediated vasodilation) were also used to assess the mechanism of antithrombotic effect. All three medicines have significantly inhibited arterial thrombus formation in mice. According to our studies, the mechanism of antithrombotic effect is based on the inhibition of shear-induced platelet reac- tivity and stimulation of endothelial function (Unseiin). It is assumed that the common ingredients Japanese Angelica Root, Cnidium Rhizome, Peony Root and Rehmannia Root could be responsible for the observed antithrombotic effect.

Improvement of decocting method for Kampo medicines using a microwave oven to extend its applications in clinical practice

Decoction of Kampo medicines plays an important role in clinical practice, especially in individualized treatment, while the inconvenience and a long time requirement of the decocting process are impediments to its widespread use in Japan. In this study, we improved the decocting method by using a microwave oven such as those found in most kitchens. To validate the feasibility and safety of this new method, we decocted kakkonto, which is the most widely used formula in clinical treatment in Japan, and keishikabushito, which contains toxic components using a microwave oven. Regarding the contents of 8 characteristic components in the kakkonto decoction and the contents of 6 toxic components in the keishikabushito decoction as indices, and with the extraction and detoxification effects equal to those of the conventional decocting method as targets, we optimized the decocting conditions with Response Surface Methods. With this new method, it took 35 min to obtain almost the same extraction effect for kakkonto as with the conventional decocting method, which takes 40 min;meanwhile, it took only 45 min to detoxify keishikabushito, which takes 60 min using the conventional decocting method. Decocting Kampo medicines with a microwave oven is feasible and as safe as the conventional decocting method. It is a convenient, safe, time-saving method, and may be applied widely in clinical practice. This innovation should allow more patients to benefit from decoction and the individualized treatment it offers.

Modulation by anti-oketsu formulations in Kampo medicine of human arterial stiffness

Objective:In traditional herbal medicine(Kampo medicine in Japan),'sho'is diagnosed by the traditional assessments of clinical conditions.Among a variety of the shos,there is an'oketsu'syndrome,which is a stagnation and disturbance of microcirculation.The prompt effects of four anti-oketsu formulations in Kampo medicine on cardiovascular functions were compared in oketsu and non-oketsu persons.Methods:The arterial pulse wave from radial artery is formed by the combination with ejection and reflection pulses.An augmentation index(AI),a ration of the ejection and reflection pulses,indicates a degree of arteriosclerosis.For both seventy-six students with oketsu and thirty-seven students with non-oketsu,Kampo formulations overcoming oketsu of Tokishakuyakusan(TS,Dang-Gui-Shao-Yao-San),Kamishoyosan(KS,Jia-Wei-Xiao-Yao-San),Keisibukuryogan(KB,Gui-Zhi-Fu-Ling-Wan)and Tokakujokito(TJ,Tao-He-Cheng-Qi-Tang)were taken once,and then,the cardiovascular functions including blood pressure,heart rate,central arterial blood pressure(CBP)and AI were examined for 60 min.Results:At 40-60 min after an intake,these formulations decreased the AI almost by 6-18%(n=76),by 18.3±3.1%(P<0.01,n=15)with TJ.Simultaneously,the CBP was reduced by 9.0±1.8%(P<0.05,n=23)with KS and by 9.1±2.0%(P<0.05,n=15)with TJ.On the other hands,non-oketsu group had less or no effect by any kinds of the formulations.Conclusion:The anti-oketsu formulations can exert the ameliorative action for oketsu persons via decreasing AI and CBP.

Development and Future Trends of Traditional Kampo Medicine in Japan

Traditional Kampo medicine is based on traditional Chinese medicine,which spread to Japan via the Korean Peninsula in the 5th century.The practice of Kampo developed gradually under the influence of local Japanese culture and prospered until the Meiji Restoration.Kampo appeared in schools successively,such as the School of Later Developments,the School of Classic Methods,the School of Textual Research,and the Integrated School.However,the practice of Kampo gradually declined after the Meiji Restoration.Today,through the continuous efforts of knowledgeable Japanese Kampo practitioners,the practice of Kampo has entered a new era as an indispensable aspect of contemporary Japanese medicine.

Standards of Reporting Kampo Products (STORK) in research articles

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials （CONSORT） checklist, we hereby propose the use of the Standards of Reporting Kampo Products （STORK） website, http：//mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

Potential of non-Western medicines in chemoradiotherapy for cervical cancer

This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’lives.Currently,most treatments are supportive,with no specific treatment options available in Western medicine.Non-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical cancer.Despite these potential benefits,challenges such as limited evidence and restricted application areas persist.While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.

Traditional Japanese Medicine,Kampo:Its History and Current Status

Traditional Japanese medicine,Kampo,is used by over 80%of medical doctors in Japan.Owing to its high quality and safety,Kampo has been integrated into modern medicine,and there are 345 randomized controlled trials using Kampo in Japan as of 2010.Although there are a number of articles in top journals about basic science research,we can find only small numbers of high-quality clinical evidence.Since undergraduate education on Kampo has been established,integrative approach with the balanced combination of modern medicine and Kampo is expected to generate good clinical evidence in the near future.

Effect of Saikokeishito, a Kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts

OBJECTIVE： Saikokeishito（TJ-10） is a Kampo（traditional Japanese herbal） medicine, clinically used for hundreds of years in East Asia. Among its various mechanisms elucidated so far, TJ-10 inhibits the production of transforming growth factor-β1（TGF-β1） and development of pancreatic fi brosis in vivo. Oxidative damage of normal human dermal fi broblasts（NHDFs） in the corium is a cause of human dermal senescence. Our aim was to determine whether TJ-10 protects NHDFs from premature senescence by hydrogen peroxide（H2O2）. METHODS： Premature senescence was induced in NHDFs by 200 μmol/L H2O2 for 4 h. Cell viability and the expressions of p53, AMP-activated protein kinase α1（AMPKα1）, AMPKα2, and 14-3-3 protein sigma（14-3-3 σ） were measured in NHDFs treated with TJ-10 for 48 h before exposure to H2O2 for 4 h. RESULTS： Cell viability after treatment with 200 μmol/L H2O2 for 4 h was similar（about 80%） to after pre-treatment with TJ-10. Ascorbic acid as a control did not protect NHDFs from damage by 200 μmol/L H2O2. Treatment with 200 μmol/L H2O2 tended to up-regulate p53 and to down-regulate SIRT1 and AMPKα1, but had no effect on AMPKα2 and 14-3-3 σ expression. Pretreatment with TJ-10 inhibited H2O2-induced up-regulation of p53 and enhanced AMPKα1 expression. CONCLUSION： It is suggested that Saikokeishito has a protective effect on oxidative stressinduced senescence of NHDFs.

Prolapsed tongue papilloma cured by administration of the traditional Japanese(Kampo) herbal medicine, Keishibukuryogan-ka-yokuinin:A case report

Squamous papilloma is a benign mass lesion of the oral mucosa. For papillomas of the tongue, surgery is recommended owing to their malignant potential;however, certain complications may be associated with surgery. A traditional Japanese(Kampo) herbal medicine, Keishibukuryogan-ka-yokuinin(KBGY),has been used to treat viral warts and various skin diseases in Japan. Therefore, the effect of KBGY on papillomas is promising. A 49-year-old Japanese man presented with a wart on his tongue that was about3 months old. He smoked 5 cigarettes per day. He did not drink alcohol. He had no history of malignant illnesses. He was taking alprazolam for panic disorder. The patient was diagnosed with a suspected papilloma of the tongue at the Department of Otolaryngology and was advised to undergo an excision biopsy to exclude malignancy. However, he refused owing to the fear of an invasive procedure. After informed consent was obtained from the patient, KBGY was prescribed. Three months later, the wart on his tongue spontaneously prolapsed. The histopathological diagnosis was squamous papilloma. There was no indication of malignancy, and the patient discontinued Kampo treatment. He has had no recurrence in the past 3 years. KBGY is a combination of Keishibukuryogan and yokuinin(adlay seeds).Keishibukuryogan may be beneficial for skin or oral mucosal remodeling, and yokuinin may have antiviral properties. The present case report suggests the use of KBGY as an appropriate complementary therapy for squamous papilloma.

The Influence of Shanghanlun on Japanese Kampo Medicine

Shanghanlun is a classic work in traditional Chinese medicine(TCM),which systematically discusses diagnosis and treatment ideas based on syndrome differentiation and records a large number of highly practical prescriptions.When Shanghanlun was introduced into Japan along with the communication between China and Japan in the Sui and Tang Dynasties,it had a profound influence on the development of Kampo medicine in Japan.By sorting out the works related to Shanghanlun in the medical history literature of Kampo medicine before the Meiji Restoration,this paper discusses the relationship between Shanghanlun and the Koho school of Kampo medicine,as well as the influence of the thought“formula corresponding to pattern identification,”originating from the Koho school,on the development of modern Kampo medicine.The study of Shanghanlun by Kampo medicine nowadays not only attaches great importance to clinical practicality but also has theoretical discussions.It is expected that future medical exchanges between China and Japan will complement each other from the perspectives of both sides and promote the theoretical and clinical development of TCM.

Reflections on the Research Status of Kampo Medicine:A Most Rewarding Visit to Japan

Traditional medicine in Japan originated from Chinese medicine （CM）, on the basis of which the abdominal diagnosis and treatment by differentiation of diseases were developed. It was also called Kampo medicine （KM）, natural medicine or oriental medicine. KM had been on the verge of extinction by suffering from serious loss during the Meiji Restoration, and only started to revive in the beginning of the 1950s, and has had considerable progress up to now.

日本汉方药物的妊娠期和哺乳期风险评估及对我国中成药的影响

目的:通过对日本汉方药物的药品说明书进行妊娠期和哺乳期风险分析,评估日本汉方药物的用药风险及其对于我国中成药妊娠期风险评估的影响,为进一步开展我国中成药的妊娠期和哺乳期风险评估提供借鉴及参考。方法:针对日本医药品与医疗器械局平台收集及整理的148种医用日本汉方药物相关药品说明书,分析妊娠期和哺乳期相关表述,评估具有用药风险的日本汉方药物及中药组分。结合我国《中华人民共和国药典:一部》(2020年版)、《中药药物警戒》和《中药药性论》等中药典籍,对日本汉方药物可能存在的妊娠期潜在风险进行评估。基于日本汉方药物妊娠期风险中药组分,对我国505种中成药进行妊娠期风险评估,分析其对我国中成药妊娠期风险的影响。结果:日本148种日本汉方药物中,存在妊娠风险的药物共39种。妊娠期风险的中药组分包括大黄、牡丹皮、附子、桃仁、牛膝、芒硝和红花,主要为自身毒性及对于流产、早产的影响。哺乳期风险日本汉方药物中,因含有大黄而易引起新生儿腹泻的药物共18种。根据我国典籍评估,日本汉方药物具有潜在风险共93种。依据日本汉方药物风险组分,我国505种中成药中具有妊娠期潜在风险的药物共59种,占345种未标注妊娠期禁忌药物种类的17.1%。结论:日本汉方药物基于妊娠期和哺乳期风险的中药组分对其日本汉方药物成药风险进行评估,其特殊人群的风险表述方法对我国中成药发展具有一定的借鉴意义。

日本汉方医学与中医药文化安全

在文化安全视域下从日本对汉方医学知识产权与专利的保护、对我国道地中药材资源的控制采购、汉方制剂的标准化品质管理和汉方医学的创新发展四方面探讨其对中医药文化安全的影响,由此从提高创新能力、加强知识产权和道地中药材的保护、提升国际软实力方面提出维护中医药文化安全之举措。面对来自日本汉方医学的挑战,需要着力提升中医药文化。

远田裕政对《伤寒论》及汉方现代化学术思想研究

当代日本汉方学者远田裕政(1934-2003年)师从千叶古方派创始人奥田谦藏,著有《伤寒论再发掘》及《现代汉方》系列论著。本文浅略总结远田裕政于《伤寒论》研究及汉方现代化体系的经方学术思想,其对康治本《伤寒论》条文及方药研究深入,试图找到《伤寒论》条文原始状态与经方演进过程,提出药基的概念和个体病理学理论,总结现代化药证,设立基本八方分类法,以结构式图示化解构经方和后世方。远田裕政具有大胆开拓探索精神,在汉方现代化上做出勇敢的尝试,中医现代化发展亦要求进行核心理论的现代化,促使中医更好地走向世界。

名古屋玄医与日本汉方医学之自立

名古屋玄医借医学复古对金元医学的非难首次打破了中国医学在日本的权威地位,之后更是提出医道规矩,试图使汉方医学区别于中国医学而自立。从历史的角度来看,日本医界的陈陈相因是他打破原有理论的原因,构建新的医学体系的动机更多是为了证明“和胜汉”说在医学领域的成立。从学术思潮传播的角度而言,玄医很大程度上受中国的错简重订派与温补学派的启发。玄医的医学反思,打破了汉方医学对中国医学的绝对依附,其思想也深刻参与构建了古方派的医学体系。

近代日本医学范式转换的历史与逻辑

历史上日本长期学习借鉴中国医学并建立起了本国的“汉方医学”体系,西方传教和商贸活动将西方医学代入日本,使日本在18世纪至19世纪完成了医学领域的全盘西化过程,发生了以汉方医学逐渐消亡为结局的向西医学范式的全面转换。汉方医学的不同学派本身具有改变医学认知方式的意愿,西医学的科学性质和知识体系为医学范式的转换提供了强大的动能。西方世界的对外扩张和日本自身的社会变革,都为近代日本医学范式转换提供了条件和土壤,是医学领域内部与外部社会环境共同作用的结果。

日本汉方药企业专利布局分析——以株式会社津村为例

目的 对株式会社津村2000—2022年申请的日本专利和中国专利进行分析,了解其技术研发及专利布局方向,并挖掘其战略处方专利布局,以期对我国中药企业有所启示。方法 在Incopat专利检索数据库上检索2000—2022年株式会社津村申请的专利,对其进行专利标引及专利技术分析。结果 株式会社津村围绕汉方制剂产业链上下游技术开展专利布局,专利布局连续且技术主题丰富,对我国中药企业具有潜在威胁,战略处方专利布局具有策略性。结论 我国企业要制定灵活的专利布局策略,拓宽中药企业专利布局技术覆盖范围,持续研发投入并做好专利防御,策略性搭建重点中药产品专利网。

汉方医家浅田宗伯在日本霍乱大流行时期的贡献

浅田宗伯是日本近代最重要的汉方医家之一,他在日本霍乱大流行时期(1858—1860)的活动与贡献迄今为止未受到学界关注。本文考察了浅田宗伯在霍乱大流行时期抗击霍乱的活动。1858年7月霍乱在江户爆发后,浅田宗伯深入疫区,成功救治大量霍乱病人,撰著、刊刻霍乱应急手册《暴泻须知》供疫区民众使用。此后到1860年,浅田宗伯相继编撰了《治瘟编》、《治瘟编补》、《治瘟编考证》。其中《治瘟编》最具临床与学术价值,推动了汉方医家对霍乱的研究与讨论。浅田宗伯对真性霍乱的命名以及对霍乱病因、传播途径的认识不及清代医家,但对霍乱的诊断与治疗颇具特色。与兰医绪方洪庵对比,浅田宗伯经过临床实践,参阅中、日及西方医书后才推广他的个人经验与治法,更为谨慎。