Japanese Kampo Medicines Research Articles

Atractylodin, β-eudesmol, and (+)-hinesol in Atractylodes chinensis rhizomes improve glomerular injuries in high immunoglobulin A mice

Background: The rhizome of Atractylodes chinensis (Asteraceae), a crude drug of Japanese Kampo medicines, has been administered to patients with edema, nephrotic syndrome, and gastrointestinal disorders. Essential oils, such as sesquiterpenoids (e.g., β-eudesmol and hinesol) and atractylodin, are rich in the rhizomes. Previously, we discovered that atractylodin, a polyacetylene compound, found in an ethyl acetate (EtOAc)-soluble fraction from a methanol extract of A. chinensis rhizomes, possessed marked anti-inflammatory activities. Oral administration of the EtOAc-soluble fraction reduced immunoglobulin A (IgA) deposition in the renal glomeruli of high immunoglobulin A (HIGA) mice, a model of human IgA nephropathy. An increased serum IgA forms immune complexes and causes the deposition on renal glomeruli, leading to inflammation by the complement-mediated pathway. Objective: The aim of this study is to identify the compounds that reduce IgA deposition in an EtOAc-soluble fraction of A. chinensis rhizomes. Methods: Metabolites in the serum of HIGA and control BALB/c mice were analyzed by gas chromatography–mass spectrometry. A standard diet including each compound was fed to HIGA and BALB/c mice for 20 weeks to evaluate the improvement of glomerular IgA deposition. Results: Metabolomic analysis of serum suggested that the HIGA mice exhibit a state near the early stage of chronic kidney disease, compared with the BALB/c mice. When mice were orally administered each hydrophobic compound of A. chinensis rhizomes, it was revealed that atractylodin, as well as β-eudesmol and (+)-hinesol, efficiently inhibited glomerular IgA deposition. Furthermore, the renal levels of complement component 3 (C3) and proinflammatory cytokine mRNAs were decreased, when the hydrophobic compounds were orally administered to HIGA mice. Conclusion: Atractylodin, β-eudesmol, and (+)-hinesol may inhibit glomerular IgA deposition, probably by attenuating complement-mediated injuries and suppressing proliferation of mesangial cells in the renal glomeruli. These compounds might improve the pathological findings of human IgA nephropathy. Keywords: Atractylodes chinensis; Crude drug; Immunoglobulin A nephropathy; Metabolomics; Complement

Inhibition of compound action potentials in the frog sciatic nerve by inchinkoto, a traditional Japanese medicine used for oral mucositis

ObjectiveThis study aimed to determine the effects of traditional Japanese (Kampo) medicines used to treat oral mucositis on nerve conduction. MethodsThe effects of Kampo medicines, crude drugs, and chemical compounds on compound action potentials (CAPs) were analyzed using extracellular recordings in frog sciatic nerves. ResultsAmong the Kampo medicines, inchinkoto demonstrated the most significant reduction in CAP amplitude, with a half-maximal inhibitory concentration (IC50) of 5.4 mg/mL. Hangeshashinto, shosaikoto, hochuekkito, and juzentaihoto also showed a significant reduction. Regarding inchinkoto, Artemisiae Capillari Spica (artemisia) was the most effective crude drug, with an IC50 of 4.2 mg/mL for CAP amplitude reduction, whereas Gardeniae Fructus (gardenia) exerted no significant effect. However, the combined use of artemisia and gardenia reduced the CAP amplitude more effectively than artemisia alone, indicating a synergistic interaction. The chemical ingredient eugenol from artemisia administered at 1 and 3 mmol/L reduced CAP amplitude, whereas other chemical ingredients administered at 0.1 and 1 mmol/L had no significant effects. ConclusionsInchinkoto exhibited the most effective reduction in CAP amplitude in the sciatic nerve of frogs, primarily through the action of artemisia, with potential synergistic interaction between artemisia and gardenia.

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophy, induced by elevated levels of angiotensin II (AngII), plays a crucial role in cardiovascular diseases. Current therapeutic approaches aim to regress cardiac hypertrophy but have limited efficacy. Widely used Japanese Kampo medicines are highly safe and potential therapeutic agents. This study aims to explore the impact and mechanisms by which Moku-boi-to (MBT), a Japanese Kampo medicine, exerts its potential cardioprotective benefits against AngII-induced cardiomyocyte hypertrophy, bridging the knowledge gap and contributing to the development of novel therapeutic strategies. By evaluating the effects of six Japanese Kampo medicines with known cardiovascular efficiency on AngII-induced cardiomyocyte hypertrophy and cell death, we identified MBT as a promising candidate. MBT exhibited preventive effects against AngII-induced cardiomyocyte hypertrophy, cell death and demonstrated improvements in intracellular Ca2+ signaling regulation, ROS production, and mitochondrial function. Unexpectedly, experiments combining MBT with the AT1 receptor antagonist losartan suggested that MBT may target the AT1 receptor. In an isoproterenol-induced heart failure mouse model, MBT treatment demonstrated significant effects on cardiac function and hypertrophy. These findings highlight the cardioprotective potential of MBT through AT1 receptor-mediated mechanisms, offering valuable insights into its efficacy in alleviating AngII-induced dysfunction in cardiomyocytes. The study suggests that MBT holds promise as a safe and effective prophylactic agent for cardiac hypertrophy, providing a deeper understanding of its mechanisms for cardioprotection against AngII-induced dysfunction.

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

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.

No association between major congenital malformations and exposure to Kampo medicines containing rhubarb rhizome: A Japanese database study.

Traditional Japanese (Kampo) medicines containing rhubarb rhizome are prescribed for constipation during pregnancy; however, detailed safety information of their use for pregnant women is lacking. The aim of current study was to clarify the association between prescription Kampo-containing rhubarb rhizome (KRR) in the first trimester of pregnancy and congenital malformations in newborns. Using a large Japanese health insurance claims database, we included pregnant women who enrolled the same health insurance society from 3months before pregnancy to the delivery date, who gave birth between 2010 and 2019, and those with data related to their infants. Pregnant women who were prescribed magnesium oxide (MgO), commonly used for constipation, during the first trimester of pregnancy and their infants were extracted as controls. Associations between KRR prescribed in the first pregnancy trimester and major congenital malformations (MCM) in the infants were examined using multivariate logistic regression analysis. Of 75,398 infants, 4,607 (6.1%) were diagnosed with MCMs within the first year after birth. Furthermore, 9,852 infants were born to women prescribed MgO, among whom 680 (6.9%) had MCMs; 450 infants were born to women prescribed KRR, among whom 28 (6.2%) had MCMs. Multivariate logistic regression analysis identified no difference in MCM risk between the two types of prescriptions [crude odds ratio (OR) 0.895, 95% confidence interval (CI) 0.606-1.322, adjusted OR 0.889, 95% CI 0.599-1.320]. In conclusion, the risk of MCMs did not differ between those prescribed KRR or MgO in the first trimester of pregnancy.

Development of Highly Sensitive Chemiluminescence Enzyme Immunostaining Assay to Determine Glycyrrhizin Content Using Anti-glycyrrhizin Monoclonal Antibody

Licorice, the root of Glycyrrhiza spp., is used in a large number of herbal medicines, such as traditional Chinese medicines, Japanese Kampo medicines, and therapeutic drugs. Since glycyrrhizin (GL) is among the main components in licorice and exhibits numerous beneficial pharmacological activities, the content of GL directly affects biological activity. The quality control based on GL content is an important factor in ensuring biological activity; however, the content of GL in licorice varies depending on plant cultivation environment, genetic factors, and species type. Previously, we prepared an anti-GL monoclonal antibody (anti-GL mAb) and employed it in various immunochemical assays for quality control of licorice and licorice-based products. In this study, we employed the anti-GL mAb in chemiluminescence enzyme immunostaining (CLEIS) to develop a very simple, rapid, specific, and sensitive quality control assay for licorice products, with a limit of detection of 3.9 ng. Furthermore, the CLEIS assay enabled semiquantitative analysis of GL in Kampo medicines. Our results showed that multiple samples can be simultaneously analyzed using CLEIS, and it is a useful tool for determining GL content, as well as ensuring chemical quality control of licorice-containing products and herbal medicines.

Safety of Japanese herbal Kampo medicines for the treatment of depression during pregnancy.

To clarify the fetal safety of herbal Kampo medicines, including Hange-koboku-to, Koso-san, Nyoshin-san, Yokukansan, Yokukansan-kachinpi-hange, Saiko-keishikankyo-to, Keishi-karyukotu-borei-to, and Kanbaku-taisou-to, when administered to pregnant women with depression using a large healthcare administrative database. We extracted data from the JMDC Claims Database (2005-2018) for this retrospective cohort study of pregnant women aged 19 years or older admitted to obstetric clinics or hospitals for delivery. Participants were classified into four groups: those without depression, those diagnosed with depression without medication, those given Kampo medicines for depression, and those given western medicines for depression. Neonatal outcomes (congenital anomalies, low birth weight, and preterm birth) were considered as the safety outcome measures. We identified 179 707 eligible mothers. The adverse outcomes did not differ significantly between participants receiving Kampo medicine and those not diagnosed with depression during pregnancy. The proportion of low-birth-weight neonates did not differ significantly between the Kampo medicine and non-depression groups (adjusted odds ratio [aOR] 1.28; 95% confidence interval [CI] 0.86-1.91), but was significantly higher in the unmedicated depression group (aOR 1.31; 95% CI 1.07-1.61) and western medicine group (aOR 1.47; 95% CI 1.18-1.83). Kampo medicines are safe for treating depression during pregnancy without increasing the incidence of congenital anomalies, low birth weight, or preterm birth.

The Clinical Practice for Hippocampal Neurogenesis by Chronobiological Therapy

The hippocampal neurogenesis in rats has been studied. In addition, when enough activities are provided in daytime, it is suggested that the memory consolidation during sleep will be achieved by hippocampal neurogenesis. We introduce our clinical practice of the chronobiological therapy regarding six dementia cases. Our therapy is based on awakening-sleep rhythm. We performed the medication to promote the changes from sleep to awakening in morning and to stabilize non-REM sleep at night. We also treated the autonomic nervous disorders so that the internal organs became active with Japanese Kampo Medicines, which were integrated with Western medicines. We set our occupational therapy in the daytime. The clinical evaluation was performed by psychological examinations and voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) of MRI. As for Z-score showing the hippocampal atrophy in VSRAD we accomplished the improvement of 0.55 points from 0.03 about six dementia cases by the chronobiological therapy. These improvements were accompanied by the better changes of the cognitive functions. We speculate that the hippocampal neurogenesis may be derived by reconstructing awakening-sleep rhythm.

Oxalic acid in ginger specifically denatures the acrid raphides in the unprocessed dried tuber of Pinellia ternata

Abstract Objective: Pinellia Tuber, the dried tuber of Pinellia ternata, is widely used in Japanese Kampo medicines and traditional Chinese medicines. The unprocessed Pinellia Tuber is known to cause very strong acrid irritation at oral and laryngopharynx mucosa. Recent studies have shown that the sharp needle-like crystals called raphides, that are composed of calcium oxalate and proteins, are the main causative substances of the irritation. Ginger, the rhizome of Zingiber officinale, has been used in the processing to reduce the acridity of Pinellia Tuber since before the sixth century, however, the mechanisms of reducing acridity have not been scientifically proved yet. Methods: We developed the raphides denaturation assay (RDA) to quantify the degree of denaturation in the raphides to cause irritation. By their lipophilic characters, the raphides could be extracted in petroleum ether (PE) layer from powdered Pinellia Tuber suspended in water, and the contents of the raphides in PE layer were measured by the absorbance. By this assay, we conducted the activity-guided fractionation from the boiling water extract of ginger to find the ingredients to denature the raphides. We also conducted the gustatory tests to detect the change of the irritation of the denatured raphides. Results: The treatment of powdered Pinellia Tuber suspension with ginger extract reduced the distribution of raphides in PE layer in RDA in a concentration-dependent manner. The activity-guided fractionation using RDA revealed that oxalic acid was the main active ingredient in ginger extract to denature the raphides of Pinellia Tuber. Oxalic acid reduced the lipophilicity of the raphides in the thermo-, time-, and concentration-dependent manners, and its activity was affected by pH. The treatment of powdered Pinellia Tuber suspension with oxalic acid significantly reduced its acrid irritation in gustatory test in human. Conclusions: We found that oxalic acid is the main active ingredient in ginger to reduce the acrid irritation of Pinellia Tuber.

Japanese herbal kampo medicines exert a comprehensive action through multiple ingredients acting on multiple targets: new prescriptions for Japanese herbal kampo medicines based on the elucidation of their mechanisms of action

Japanese herbal kampo medicines exert a comprehensive action through multiple ingredients acting on multiple targets: new prescriptions for Japanese herbal kampo medicines based on the elucidation of their mechanisms of action

Postoperative pharmacotherapy for patients with biliary atresia in Japan.

Members of the Japanese Biliary Atresia Society were surveyed using questionnaires that assess their current practice regarding postoperative pharmacotherapy for outpatients with biliary atresia (BA). In September 2018, questionnaires were sent to 100 member institutions of the Japanese Biliary Atresia Society. Questionnaires included the number of BA outpatients per institution and pharmacotherapy for outpatients with native liver. Pharmacotherapies were categorized into antibiotics, cholagogues, hepatoprotective agents, branched-chain amino acid supplement, Japanese Kampo medicine, probiotics, laxative, glycerin enema, and "others." In each category, the questionnaires asked about the medicine's details and the time of withdrawal of administration. Responses were collected from 58 of the 100 institutions. Fifty-four institutions (94.7%) had prescribed one or more medicines as postoperative pharmacotherapy, and three institutions (5.3%) did not prescribe any medicines. Fifty-three institutions (93.0%) had prescribed ursodeoxycholic acid (UDCA), and 32 (60.4%) of these continued prescribing UDCA as long as the condition of patients remained unchanged. Twenty-nine (50.9%) had prescribed Japanese Kampo medicines ("Inchinkoto" in all cases). Twenty-four (42.1%) had prescribed antibiotics, mainly trimethoprim-sulfamethoxazole, in 21 (87.5%). Twenty-three (40.4%) had prescribed probiotics. There were many variations of pharmacotherapy in BA outpatients with native liver in Japan, including antibiotic, probiotic, and Inchinkoto prescriptions. Of the various drugs, the most commonly administered was UDCA.

Traditional Japanese Kampo medicines contribute to successful withdrawal from the causative drug in medication-overuse headache

Traditional Japanese Kampo medicines contribute to successful withdrawal from the causative drug in medication-overuse headache

Identification of traditional Japanese Kampo medicines and crude drugs that upregulate brain‑derived neurotrophic factor in human peripheral cells

The neurotrophic hypothesis of depression, which suggests that decreased hippocampal brain‑derived neurotrophic factor (BDNF) levels cause depression, has become increasingly popular. BDNF, a member of the neurotrophin family, promotes neuronal differentiation and survival. BDNF is synthesized in various peripheral tissues, as well as in the brain. Considering that peripheral BDNF can be transported into the brain across the blood‑brain barrier, substances with the ability to upregulate BDNF activity in peripheral tissues may be useful in the management of depression. Previously, we demonstrated that the human kidney adenocarcinoma cell line ACHN produces BDNF; hence, this cell line was employed for screening upregulators of peripheral BDNF. Here, we aimed to identify Kampo (traditional Japanese) medicines and their crude drug components that upregulate BDNF levels using ACHN cells. Chotosan, Hochuekkito, Kososan, and Ninjinyoeito, Kampo medicines used in treating psychiatric disorders, increased BDNF levels in the culture media of ACHN cells. Furthermore, Chinpi (Citrus unshiu peel), a crude drug contained in these four Kampo medicines, as well as Onji (Polygala tenuifolia root), and Saiko (Bupleurum falcatum root) elevated BDNF levels in ACHN cells. Chinpi, showing strong BDNF elevating effect, increased BDNF mRNA expression. Inhibitors of protein kinase B, mitogen‑activated protein kinase kinase, and cAMP‑dependent protein kinase, involved in the transcription of BDNF, attenuated Chinpi‑induced BDNF elevation. Our results suggest that Chinpi and Kampo medicines containing Chinpi can promote the production of BDNF in peripheral tissues, potentially alleviating depression symptoms.

Prescription of Kampo Formulations for Pre-natal and Post-partum Women in Japan: Data From an Administrative Health Database.

Introduction: Traditional Japanese (Kampo) medicines are often prescribed for women in Japan before, during, and after pregnancy. However, detailed information on the actual frequency of use and safety of Kampo preparations during pregnancy is lacking.Aim: To investigate the frequency of prescription of Kampo medicines for pregnant women in Japan.Methods: Information on Kampo medicines prescribed during outpatient care and hospitalization of selected mothers from January 2005 to August 2016 were extracted from the Japan Medical Data Center (Tokyo, Japan), which is a large claims database.Results: Of the 33,941 subscribers identified from the database, 16,294 (48%) received at least one prescription of a Kampo medicine. Kakkonto was the formula most prescribed during the study period, followed by shoseiryuto and tokishakuyakusan. In the 180 days before pregnancy, the most prescribed medicine was tokishakuyakusan, followed by kakkonto and shoseiryuto. Shoseiryuto, tokishakuyakusan, and kakkonnto were the formulae most prescribed during pregnancy. The most prescribed medicines during the 180 days postpartum were kakkonto, shoseiryuto, and saireito.Conclusions: Information in the Japanese insurance system shows that Kampo medicines are often prescribed during pregnancy. Most of these prescriptions are generally used for the treatment of common cold. Tokishakuyakusan in particular is usually used in the treatment of various symptoms of pregnancy. Further research is needed to clarify the relationship between the use of Kampo medicines during pregnancy and adverse events in infants in Japan.

Kakkonto Inhibits Cytokine Production Induced by Rhinovirus Infection in Primary Cultures of Human Nasal Epithelial Cells.

Rhinovirus (RV) is a primary etiologic agent of common cold that can subsequently acutely exacerbate bronchial asthma or chronic obstructive pulmonary disease. Kakkonto (Ge-gen-tang in Chinese), one of the most frequently prescribed traditional Japanese (Kampo) medicines, is used for treating common cold, shoulder stiffness, or inflammatory diseases of the upper body. Previous experimental studies have indicated that kakkonto exerts antiviral and anti-inflammatory effects on the influenza virus and the human respiratory syncytial virus. However, there is a lack of reports investigating the efficacy of kakkonto in RV infection. Hence, the aim of the current study was to investigate the effects of kakkonto on RV infection of human nasal epithelial (HNE) cells. HNE cells obtained via endoscopic sinus surgery were cultured and infected with RV14, with or without kakkonto treatment. The supernatants from the cells were collected, and the RV14 titer and cytokine levels were assessed. Reverse transcription-polymerase chain reaction was performed to determine the amount of viral RNA, while the level of nuclear factor kappa B (NF-κB) subunits in the nucleus was assessed by enzyme-linked immunosorbent assay. Although kakkonto treatment did not reduce RV14 titer or RNA levels, indicating that it did not inhibit RV14 proliferation, it was found to reduce the production of specific pro-inflammatory cytokines, including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein-1 (MCP-1). Unlike that observed with the kakkonto extract, none of the crude drugs contained in kakkonto reduced IL-8 level. Furthermore, though kakkonto treatment significantly reduced p50 levels, it did not impact the p65 subunit of NF-κB. These results indicated that kakkonto can inhibit inflammation caused by RV infection and may exert an immunomodulatory effect on HNE cells. This is the first report to elucidate the effects of kakkonto extract on RV infection in primary cultures of HNE cells, providing evidence that kakkonto may act as an effective therapy for RV infection and subsequent airway inflammation.

Medication Overuse Headache Successfully Treated by Three Types of Japanese Herbal Kampo Medicine

Medication overuse headache (MOH) usually resolves after the overuse is stopped and starting prophylactic medications. However, it can be challenging to prescribe common prophylactic medications when patients have a history of side effects. As an alternative therapy, traditional Japanese herbal kampo medicine can be used. We herein report a case of a MOH woman with a history of side effects by such common prophylactic medications. A 50-year-old woman presented with a severe migraine attack. She had suffered from migraines for 10 years. She had taken loxoprofen and sumatriptan every day for over eight years. As prophylactic medications, lomerizine, valproic acid, and amitriptyline had been prescribed in the past, but they were discontinued due to side effects. Therefore, she could continue only propranolol as prophylactic medication. She had severe pulsatile headaches and nausea every day. We diagnosed triptan- and non-steroidal anti-inflammatory drug-overuse headache (the International Classification of Headache Disorders 3rd edition code 8.2.2 and 8.2.3.2) and chronic migraine (code 1.3). She was admitted and stopped loxoprofen and sumatriptan. We prescribed three types of Japanese herbal kampo medicines - kakkonto (TJ-1), goreisan (TJ-17), and goshuyuto (TJ-31). Her headache was relieved on day 5, and she was discharged on day 7. In the 40 days after discharge, she had only three times mild headaches with a numeric rating scale (NRS) of 2/10. She did not need any triptans nor anti-inflammatory drugs. We herein presented the MOH woman who was successfully treated using three types of kampo medicine. We should pay attention to their side effects, but kampo medicine may be useful for MOH treatment as acute and prophylactic medications for primary headaches.

インフルエンザなどの急性ウイルス性呼吸器感染症パンデミック/エピデミックに対する和漢治療の歴史─麻黄の品質とその治療効果への影響

スペイン風邪の際に漢方治療が多くの命を救ったことはよく知られる。古来よりインフルエンザを初めとした急性ウイルス性呼吸器感染症は傷寒などと呼ばれてきたが，本邦ではその治療にあたり，『傷寒論』『小品方』『太平恵民和剤局方』『万病回春』などから多くの処方が取り入れられてきた。江戸期には漢方治療は本邦独自の発展を遂げるものの，医療及び経済的な格差のため，その恩恵を受けた庶民は少数派であった。さらに傷寒治療のキードラッグである麻黄には，古来よりトクサ属植物と混同されるなど品質面に大きな問題を抱え，その薬効が過小評価されてきた可能性があることは，今後も留意すべきものと思われる。新型インフルエンザ・コロナウイルスパンデミックにも，漢方の有効性が期待されている。しかしその力を十分に引き出すには，十分なレベルの知識のもと方剤を適正に使用することの重要性が，今回歴史を振り返ったことにより再認識させられた。

Effect of Japanese herbal Kampo medicines on live birth rate in women with recurrent pregnancy loss.

To determine the effectiveness of Japanese Kampo medicines on the overall live birth rate among patients with recurrent pregnancy loss (RPL) in a real-world setting. In the current retrospective cohort study, we used the JMDC Claims Database to extract information on women diagnosed with RPL between January 1, 2005 and August 31, 2018. Eligible women were divided into two groups according to Kampo medicines administered as treatments for RPL. The primary outcome was the live birth rate during the study period. Propensity score matching, Kaplan-Meier cumulative incidence plots, log-rank test, and Cox proportional-hazards regression model were used to compare the primary outcome between patients with and without Japanese herbal Kampo medicines. Among 5517 eligible patients, 1652 used Kampo medicines and 3865 did not. After propensity score matching, the live birth rate at 2.0years was 15.7% in the Kampo group and 11.2% in the non-Kampo group. At 4.0years, the difference between the two groups had slightly increased. The overall live birth rate differed significantly between the two groups (hazard ratio 1.32, 95% confidence interval 1.13-1.53; P<0.001). Japanese herbal Kampo medicines may improve the live birth rate in patients with RPL.

Yokukansankachimpihange, a traditional Japanese (Kampo) medicine, enhances the adaptation to circadian rhythm disruption by increasing endogenous melatonin levels

The traditional Japanese (Kampo) medicines yokukansan (YKS) and yokukansankachimpihange (YKSCH) have similar formulas and the same indications. In animals or cultured cells, the neuropharmacological actions of YKS are sometimes more beneficial than those of YKSCH. Since both drugs are used to treat sleep disorders in Japan, we examined the ameliorative effects of YKS and YKSCH on circadian rhythm disturbance and compared their efficacy using a mouse model of circadian rhythm disruption. Ramelteon was used as the positive control. Ramelteon treatment significantly reversed decreased running wheel activity during the advanced dark phase, indicating facilitation of circadian adaptation. YKS treatment also reversed the activity in the early period of drug treatment; however, it was not statistically significant. YKSCH treatment significantly reversed the decreased activity during the advanced dark phase. Plasma melatonin (MT) levels were significantly increased in the YKSCH but not in the YKS group. The ameliorative effect of YKSCH on rhythm disruption was significantly inhibited by coadministration of the MT2 receptor antagonist. Therefore, the therapeutic effect of YKSCH on circadian rhythm disruption would be attributable, to elevated endogenous MT levels. Taken together, YKS and YKSCH have different pharmacological properties and may be more precisely prescribed depending on patients' psychological symptoms.

The effects of TJ-14 (Hange-shashin-to), Japanese kampo medicines, on spontaneous electrical activity of circular smooth muscle cells in the mouse proximal colon

The effects of TJ-14 (Hange-shashin-to), Japanese kampo medicines, on spontaneous electrical activity of circular smooth muscle cells in the mouse proximal colon