Comparative study of the effects of the three kinds of Kampo-hozai: Ninjinyoeito, Hochuekkito, and Juzentaihoto on anxious and low sociability behavior using NPY-knockout zebrafish.

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.

Juzentaihoto Suppresses Muscle Atrophy in KKAy Mice.

In obese patients with type 2 diabetes, reduced insulin sensitivity, increased production of inflammatory cytokines, and increased oxidative stress were observed, which lead to decreased protein synthesis and increased proteolysis in the skeletal muscles. Juzentaihoto (JTT) is herbal medicine and we have previously reported that the administration of JTT hot water extract alleviates skeletal muscle atrophy in a mouse model with streptozotocin-induced type 1 diabetes. In this study, we evaluated the inhibitory effects of JTT on muscle atrophy in a mouse model with obesity and type 2 diabetes. JTT was administered to KKAy mice with type 2 diabetic obesity and its effects on the skeletal muscles were evaluated. After JTT administration in KKAy mice, the wet weight and muscle fibre cross-sectional area of gastrocnemius increased and the time duration of exercise in the rotarod test improved. In addition, the serum levels of tumour necrosis factor-α and interleukin-6 decreased, adiponectin levels increased, and homeostasis model assessment for insulin resistance improved. Furthermore, JTT administration decreased the mRNA levels of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1), increased the mRNA levels of Sirtuin1 in gastrocnemius. Our results suggest that JTT improves insulin resistance, suppresses inflammation, and reduces oxidative stress in KKAy mice, thereby suppressing skeletal muscle atrophy. JTT administration in clinical practice is expected to improve muscle atrophy in patients with obesity and type 2 diabetes.

Juzentaihoto Exerts Anti-Allergic Effects by Inhibiting Effector T-Cell Activation and Inducing and/or Activating Regulatory T Cells in a Murine Model of Contact Hypersensitivity.

BACKGROUND: Juzentaihoto (JTT) is a Kampo prescription that has been used clinically for treating skin diseases such as atopic dermatitis in Japan. We have previously studied the anti-allergic effects of JTT on 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) in mice and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying the anti-allergic actions of JTT is obscure. METHODS: We investigated the mechanism underlying the anti-allergic effects of JTT using a TNCB-induced murine CHS model and adoptive cell transfer experiments. RESULTS: We showed that the anti-allergic effects of JTT are due to inhibition of effector T-cell activation and induction and/or activation of regulatory T cells. Furthermore, ex vivo experiments confirmed the effect of JTT on the activation of effector T cells and regulatory T cells, as interferon-γ production decreased, whereas interleukin (IL)-10 production increased, in the cultured lymphocytes obtained from 5% TNCB-sensitized mice treated with anti-CD3ε and anti-CD28 monoclonal antibodies. Flow cytometry showed that the CD4+CD25+Foxp3+, CD4+CD25+Foxp3-, and CD8+CD122+ cell population increased after oral administration of JTT. Finally, the anti-allergic effect of JTT by inducing and/or activating regulatory T cells (Tregs) was confirmed to be mediated by IL-10 through in vivo neutralization experiments with anti-IL-10 monoclonal antibodies. CONCLUSION: We suggested that JTT exerts anti-allergic effects by regulating the activation of effector T cells and Tregs involved in murine CHS model.

A Case of Refractory Recurrent Genital Herpes Successfully Treated with Juzentaihoto and Saikokeishikankyoto / 日本東洋医学雑誌

A 40-year-old woman had suffered from genital herpes twice a year since approximately age 25 years. A year and a half before her first visit to our department, the frequency of her genital herpes had increased from 2 to 5 times a month. Continuous suppressive antiviral medication had not worked, and the patient was referred to our department. We discontinued the anti-herpes medication, and started treatment with Kampo (Japanese herbal) medicine. Initially, the patient’s symptoms did not improve with tokishigyakukagoshuyushokyoto for coldness of the hands and feet or hochuekkito for general fatigue. Then, on the basis of her symptoms of irritability, nightmares, dry skin and hair loss, we changed her prescription to juzentaihoto before meals and saikokeishikankyoto after meals. The frequency of genital herpes thereafter gradually decreased, and finally no further recurrences of herpes were observed as long as the patient was taking these two medicines. This result showed that some patients with recurrent genital herpes who fail to respond to antiviral therapy could be managed with Kampo medicine alone.

Combination therapy of Juzentaihoto and mesenchymal stem cells attenuates liver damage and regresses fibrosis in mice.

BACKGROUND: Liver cirrhosis is an end-stage multiple liver disease. Mesenchymal stem cells (MSCs) are an attractive cell source for reducing liver damage and regressing fibrosis; additional therapies accompanying MSCs can potentially enhance their therapeutic effects. Kampo medicines exhibit anti-inflammatory and anti-oxidative effects. Here, we investigated the therapeutic effect of MSCs combined with the Kampo medicine Juzentaihoto (JTT) as a combination therapy in a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. METHODS: C57BL/6 mice were administered JTT (orally) and/or MSCs (one time, intravenously). The levels of liver proteins were measured in the sera. Sirius Red staining and hydroxyproline quantitation of hepatic tissues and immune cells were conducted, and their associated properties were evaluated. Liver metabolomics of liver tissues was performed. RESULTS: JTT monotherapy attenuated liver damage and increased serum albumin level, but it did not effectively induce fibrolysis. JTT rapidly reduced liver damage, in a dose-dependent manner, after a single-dose CCl4 administration. Furthermore, JTT-MSC combination therapy attenuated liver damage, improved liver function, and regressed liver fibrosis. The combination increased the CD4+/CD8+ ratio. JTT had stronger effects on NK and regulatory T cell induction, whereas MSCs more strongly induced anti-inflammatory macrophages. The combination therapy further induced anti-inflammatory macrophages. JTT normalized lipid mediators, and tricarboxylic acid cycle- and urea cycle-related mediators effectively. CONCLUSIONS: The addition of JTT enhanced the therapeutic effects of MSCs; this combination could be a potential treatment option for cirrhosis.

Multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine: A case report.

FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life.

Juzentaihoto Suppresses Muscle Atrophy and Decreased Motor Function in SAMP8 Mice.

Sarcopenia is a disease whose symptoms include decreased muscle mass and weakened muscle strength with age. In sarcopenia, decreased production of insulin-like growth factor-1 (IGF-1) increases ubiquitin ligases, such as Atrogin1 and Muscle RING-Finger Protein-1 (MuRF1), by activating forkhead box O (FOXO), and inflammatory cytokines and oxidative stress increase the expression of ubiquitin ligases by activating the transcription factor nuclear factor-kappa B (NF-κB). In addition, increased levels of ubiquitin ligases cause skeletal muscle atrophy. Conversely, sirtuin 1 (Sirt1) is known to regulate the expression of ubiquitin ligases by suppressing the activities of NF-κB and FOXO. In this study, we evaluated the effect that juzentaihoto hot water extract (JTT) has on skeletal muscle atrophy and motor function by administering it to senescence-accelerated mouse prone-8 (SAMP8). The group treated with JTT displayed larger gastrocnemius muscle (GA) and extensor digitorum longus (EDL) weights, larger GA muscle fiber cross-sectional areas, and motor function decline during rota-rod tests. JTT also increased IGF-1 serum levels, as well as mRNA Sirt1 levels in GA. Serum levels of tumor necrosis factor-α, interleukin-6, and mRNA levels of Atrogin1 and MuRF1 in GA were reduced by JTT. The muscle fiber cross-sectional area of GA was correlated with the mRNA levels of Sirt1 in GA. The results of this study suggested that JTT administration suppresses skeletal muscle atrophy and motor function decline in SAMP8 mice. This effect may be associated with the increased expression levels of Sirt1 and IGF-1 by JTT.

Combination of Juzentaihoto and chemotherapy improves the prognosis of patients with postoperative recurrence of non-small cell lung cancer.

Kampo medicines have been used to reduce chemotherapy-induced adverse events. However, whether Kampo medicine can improve the prognosis of cancer remains unclear. The present study aimed to clarify the effect of Juzentaihoto (TJ-48) on patients with postoperative recurrence of non-small cell lung cancer. In total, 45 patients with postoperative recurrent non-small cell lung cancer scheduled for first-line chemotherapy were enrolled in the present study. Differences in progression-free survival between the chemotherapy combined with TJ-48 and chemotherapy only groups were analyzed. Body weight change and prognostic nutritional index were also evaluated to examine whether these factors were influenced by TJ-48 administration. Multivariate analysis was performed to detect independent prognostic factors. A significant increase was observed in progression-free survival in the chemotherapy plus TJ-48 group compared with in the chemotherapy alone group (P<0.001). Significant decreases in body weight and prognostic nutritional index score were observed in the chemotherapy alone group (P<0.01 and P<0.05, respectively); however, these decreases were not observed in the chemotherapy plus TJ-48 group. Multivariate analysis revealed that TJ-48 administration with chemotherapy was an independent prognostic factor. In conclusion, TJ-48 combined with chemotherapy may improve the progression-free survival of patients with postoperative recurrence of non-small cell lung cancer by preventing nutritional disorders.

Japanese Kampo Medicine Juzentaihoto Enhances Antitumor Immunity in CD1d-/- Mice Lacking NKT Cells.

Although the Japanese traditional herbal medicine (Kampo), Juzentaihoto (JTT), has been reported to have antitumor effects in several tumor models, its role in tumor immunology remains controversial. In the present study, we tested whether oral administration of JTT enhances antitumor immunity in CD1d-/- mice, in which immunosuppression was partially relieved due to the lack of NKT cells. In a subcutaneous murine syngeneic CT26 colorectal tumor model, JTT had no impact on tumor growth in wild type (WT) BALB/c mice. However, the growth rate of tumors was significantly slower in CD1d-/- mice than in WT mice. Surprisingly, JTT significantly delayed tumor growth in such CD1d-/- mice. In vivo depletion of CD8+ T cells revealed that CD8+ T cells are required for JTT's antitumor activity. Moreover, tumor-reactive cytotoxic T-lymphocytes were detected exclusively in JTT-treated mice with well-controlled tumors. JTT did not affect the number of tumor-infiltrating CD4+ regulatory T cells. On the contrary, JTT increased the degranulation marker CD107a+ CD8+ T cells and decreased Ly6G+ Ly6Clo polymorphonuclear myeloid-derived suppressor cells in tumor-infiltrating lymphocytes, most probably contributing to the suppression of tumor growth in JTT-treated mice. Nonetheless, JTT had no impact on the proportion of monocytic myeloid-derived suppressor cells. In conclusion, our results indicate that in the absence of NKT cells, JTT augments antitumor immunity by CD8+ T cells, suggesting that this Kampo medicine is a promising anticancer adjuvant when negative immune regulation is partially relieved.

Successfully Treated Cluster Headache with Juzentaihoto / 日本東洋医学雑誌

This report describes a case of cluster headaches that was successfully treated with juzentaihoto. A 39-year-old male had been having attacks of cluster headaches for 7 years. During an attack, he took a triptan and nonsteroid anti-inflammatory drug (NSAID), but they were not effective and he had lost his good eyesight after the attack. Recently, as the attacks had become more frequently and stronger, he visited our hospital. Physical examination including dry skin suggested that he had kikyo and kekkyo. Therefore, we prescribed juzentaihoto. After 3 months of treatment, the frequency and strength of the attacks decreased. The underlying pathophysiology of cluster headaches incompletely solved. When the responsible localization of organic disease is not clear, Western medicine sometimes have difficulty in relieving pain. On the other hand, we can analyze the case through “yin-yang and xu-shi categorization,” “life force, blood and colorless bodily fluids (3 elements that constitute an organism)” and Gozo-roppu-setsu according to traditional Chinese medicine. Understanding the bodily functions from an Oriental medicine viewpoint, we can prescribe effective oriental medicine to relieve pain.

Efficacy of Juzen-taiho-to against vincristine-induced toxicity in dogs.

Vincristine, one of the anti-cancer drugs used in veterinary practice, has adverse hematological and gastrointestinal effects in dogs. Juzen-taiho-to is a traditional Chinese medicine used for patients with anorexia in human medicine. However, the protective effects of Juzen-taiho-to against anti-cancer drug-induced toxicity in dogs have not been investigated. We therefore examined whether the administration of Juzen-taiho-to to dogs affects gastric motility, and vincristine-induced gastrointestinal and hematological toxicity. The study was composed of three trials. In the first trial, Juzen-taiho-to (450 mg/kg/day) was orally administered to five dogs. In the second and third trials, vincristine (0.75 mg/m2) was intravenously administered to each dog in the absence or presence of Juzen-taiho-to (450 mg/kg/day). During these trials, gastric motility and blood parameters were assessed. Juzen-taiho-to increased gastric motility and improved vincristine-induced gastrointestinal, but not hematological, adverse effects in dogs. This study suggested that Juzen-taiho-to may be applicable for gastrointestinal care in dogs receiving chemotherapy.

Possible anti-oxidative effects of long-term administration of Juzen-taiho-to in dogs.

It is known that oxidative stress is related to disease in humans and dogs. Many traditional Chinese medicines have been reported to have anti-oxidative effects, but there are no reports that they have anti-oxidative effects in dogs. In this study, we examined the anti-oxidative effects of Juzen-taiho-to, a traditional Chinese medicine, in dogs. Five healthy female beagle dogs (38-41 months of age weighing 8.6-10.7 kg) were orally administered Juzen-taiho-to at 450 mg/kg with food for 28 days. Blood samples were taken from all five dogs on days 0, 7, 14, 21, and 28. Using the blood samples, improvement of the antioxidant level as assessed by the biological antioxidant potential (BAP), reduced oxidative stress level as assessed by derivatives of reactive oxygen metabolites (d-ROMs), and improvement of blood fluidity were examined. Regarding the antioxidant level and blood fluidity, no significant difference was observed, but the oxidative stress level on days 14, 21, and 28 was significantly lower than that on day 0. Thus, Juzen-taiho-to may have anti-oxidative effects in dogs by reducing oxidative stress and be useful for oxidative stress-related diseases in dogs.

Combination therapy with traditional medicines for perianal abscess in children.

BACKGROUND: Combination therapy with two different traditional medicine formulations called hainosankyuto and juzentaihoto (TJ-122 and TJ-48; Tsumura & Co, Tokyo, Japan) may be effective for perianal abscess (PA), but their effectiveness has not been established. The present study investigated the effectiveness of combination therapy with TJ-122 and TJ-48 as the most effective conservative treatment for PA. METHODS: We identified 69 patients with PA under 2 years of age and divided them into four groups according to the formulations used: group 1, TJ-122 (n = 17); group 2, TJ-48 (n = 14); group 3, TJ-122 and TJ-48 (n = 19); and group 4, no traditional medicines (n = 19). Treatment was continued for 3-6 months after resolution of the PA in groups 1 and 2, and for 1 year in group 3. Age at presentation, duration of purulent discharge (PD), frequency of surgical intervention (incision and drainage [ID]; fistulotomy/fistulectomy), and recurrence rates were statistically analyzed. RESULTS: Mean age (months) was 8.6 ± 9.2, 6.9 ± 7.3, 5.2 ± 4.7, and 3.8 ± 3.1 in groups 1, 2, 3, and 4, respectively (P = n.s.). Mean PD (weeks) was 2.5 ± 2.2, 7.1 ± 10.8, 2.0 ± 0.0, and 2.7 ± 1.0, respectively. Duration of PD was significantly longer in group 2 than in groups 1 and 3 (P < 0.05). Mean number of ID procedures was 1.0 ± 0.2, 2.3 ± 0.5, 0, and 1.6 ± 0.2, respectively. Group 1 had significantly less ID than group 2 (P < 0.01). Recurrence rates were 6%, 36%, 0%, and 32%, respectively. Groups 1 and 3 had significantly less recurrence than group 2 (P < 0.05), and group 3 had significantly less recurrence than group 4 (P < 0.01). CONCLUSIONS: Combination therapy with TJ-122 and TJ-48 decreased recurrence and surgical intervention to zero in this study, demonstrating high effectiveness for treating PA in children.

Juzentaihoto Suppresses Muscle Atrophy in Streptozotocin-Induced Diabetic Mice.

In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.

Abundance of Plant-Associated Gammaproteobacteria Correlates with Immunostimulatory Activity of Angelica sinensis.

Background: Angelica sinensis is a medicinal plant known for a variety of biological effects, including its ability to stimulate innate immune cells in humans. Recent studies indicate that the immunostimulatory activity of A. sinensis arises from microbe-associated molecular patterns (MAMPs) of plant-associated bacteria. However, it is unknown which bacterial taxa in A. sinensis are responsible for the production of immunostimulatory MAMPs. Methods: Samples of A. sinensis were subjected to a cell-based assay to detect monocyte-stimulation and 16S ribosomal RNA amplicon sequencing, which revealed their immunostimulatory activity and microbial communities. The resulting data were analyzed by Linear discriminant analysis effect size (LEfSe), an online biostatistical tool for metagenomic biomarker discovery, to identify the bacterial taxonomical features correlated with the immunostimulatory activity. Results: A series of bacterial taxa under Gammaproteobacteria correlated positively with the immunostimulatory activity, whereas several Gram-positive taxa and Betaproteobacteria correlated negatively with the activity. Conclusions: The identified bacterial taxa set a new stage to characterize immunostimulatory MAMPs in plants.

Kampo Therapies and the Use of Herbal Medicines in the Dentistry in Japan.

Dental caries and periodontal disease are two major diseases in the dentistry. As the society is aging, their pathological meaning has been changing. An increasing number of patients are displaying symptoms of systemic disease and so we need to pay more attention to immunologic aggression in our medical treatment. For this reason, we focused on natural products. Kampo consists of natural herbs-roots and barks-and has more than 3000 years of history. It was originated in China as traditional medicine and introduced to Japan. Over the years, Kampo medicine in Japan has been formulated in a way to suit Japan's natural features and ethnic characteristics. Based on this traditional Japanese Kampo medicine, we have manufactured a Kampo gargle and Mastic Gel dentifrice. In order to practically utilize the effectiveness of mastic, we have developed a dentifrice (product name: IMPLA CARE) and treated implant periodontitis and severe periodontitis.

Juzentaihoto hot water extract alleviates muscle atrophy and improves motor function in streptozotocin-induced diabetic oxidative stress mice.

A decrease in skeletal muscle mass and motor function occurs in diabetic patients. In type 1 diabetic patients, in particular, fast-type fiber-dominated muscle atrophy occurs due to increased oxidative stress and inflammation. Juzentaihoto is a herbal medicine that has been found to be effective in reducing oxidative stress. In this study, juzentaihoto hot water extract (JTT) was administered prophylactically to mice with diabetic oxidative stress, which was induced by an injection of streptozotocin, and the effects on skeletal muscle mass, motor function, and antioxidant activity were evaluated. In mice that were administered JTT, skeletal muscle atrophy and loss of motor function were suppressed. Additionally, the administration of JTT increased the mRNA expression level of Sirt1 and the activity of superoxide dismutase in the gastrocnemius. In addition to skeletal muscle atrophy, atrophy of the liver, spleen and thymus gland, and kidney hypertrophy were also suppressed. Furthermore, in order to evaluate the antioxidant activity of 10 constituent crude drugs that comprise juzentaihoto, Sirt1 transcriptional activity in C2C12 cells was evaluated. The Sirt1 transcriptional activity was increased by Cinnamomi Cortex, Astragali Radix, and Glycyrrhizae Radix extracts. These three constituent crude drugs play an important function in the antioxidant action of juzentaihoto, suggesting that juzentaihoto can prevent muscle atrophy by decreasing oxidative stress.

Nine Cases of Migraine During the Late Period of Menstruation Successfully Treated with Juzentaihoto / 日本東洋医学雑誌

In female patients with migraine, the triggering or exacerbating factors for migraine including stress, menstruation and fatigue, should be treated intensively in addition to treatment for headache. Patients with coldness and weak constitution become a state of qi and blood deficiency in terms of Kampo medicine under the circumstances of severe fatigue, lack of sleep and menopausal symptoms. They tend to suffer from migraine at around the 4th or 5th day of menstrual period after rather heavy menstrual bleeding on the 2nd or 3rd day. We experienced 4 patients with headache during the late period of menstruation whose symptoms were successfully treated by juzentaihoto known to improve qi and blood. In Case 1, daily prescription was changed from unkeito to juzentaihoto. In Case 2, during the 7 days of menstrual period, juzentaihoto was added to tokishigyakukagoshuyushokyoto, while juzentaihoto was substituted for tokishakuyakusan in Case 3 and Case 4. In 9 cases of headache, including these 4 cases, juzentaihoto was efficacious against migraine headache during the late period of menstruation with coldness (9/9 cases), fatigability (9/9 cases) and dryness symptoms (7/ 9 cases). These results indicate that juzentaihoto is effective for migraine during the late period of menstruation, especially in patients with fatigue after menstrual bleeding. The administration period of juzentaihoto should be individualized for each patient depending on the severity of qi and blood deficiency.

Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media.

OBJECTIVE: Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. METHODS: Children prone to recurrent AOM aged 6-48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10-0.25g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. RESULTS: At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61±0.54 vs. 1.07±0.72 AOM instances/month; P=0.005) and also significantly decreased number of coryza episodes (P=0.015) and total antibiotic administration (P=0.024). CONCLUSIONS: This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections.

<b>Three Hemodialysis Patients with Postoperative Amputation Wounds Due to Critical Limb Ischemia Successfully Treated with Juzentaihoto and </b><b>Keishibukuryogan</b> / 日本東洋医学雑誌

<p>Peripheral arterial disease is a serious complication that can arise in hemodialysis patients. Prognosis in critical limb ischemia (CLI) due to peripheral arterial disease is extremely poor. A dialysis patient may experience symptoms of both <i>qi </i>and <i>ketsu </i>deficiency and <i>ketsu </i>stagnation during the long-term treatment of CLI. Herein, we report three hemodialysis patients with refractory postoperative skin ulcers who were successfully treated with juzentaihoto and keishibukuryogan after limb amputation. Case 1 was a 68-year-old man who had skin ulcers of the right second, third, and fifth toes. After amputation of the third toe, juzentaihoto and keishibukuryogan were initiated. Case 2 was a 67-year-old man who had skin ulcers after amputation of the left fourth and fifth toes. Postoperatively, juzentaihoto and keishibukuryogan were initiated, and good granulation was observed. Case 3 was a 76-year-old man who had skin ulcers after left below-the-knee amputation. Because of the extremely poor tissue granulation, juzentaihoto and keishibukuryogan were initiated, and good granulation was gradually observed. After an operation for CLI, prompt return to activities of daily living is desirable. The appropriate addition of Kampo treatment to Western treatment may improve chronic refractory skin ulcers.</p>