Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

AIM: Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. METHODS: We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. RESULTS: The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. CONCLUSIONS: Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Rikkunshito attenuates induction of epithelial-mesenchymal switch via activation of Sirtuin1 in ovarian cancer cells.

Rikkunshito, a traditional Japanese herbal medicine, improves appetite via activation of gastrointestinal hormone ghrelin pathway. The function of ghrelin is mediated by growth hormone secretagogue receptor (GHSR1a), and ghrelin has been known to possess diverse physiological functions including growth suppression of some cancer cells. Considering that increased ghrelin signaling by Rikkunshito could enhance sirtuin1 (SIRT1) activity in nervous system, we aimed to investigate the effect of Rikkunshito in ovarian cancer cells. Ovarian cancer cell lines were treated with Rikkunshito, and cellular viability, gene expressions and epithelial-mesenchymal transition (EMT) status were investigated. To investigate the involvement of SIRT1 by Rikkunshito in SKOV3 cancer cells, endogenous expression of SIRT1 was depleted using small interfering RNA (siRNA). Treatment with Rikkunshito elevated ghrelin, GHSR1a and SIRT1, while cellular viability was decreased. The treatment of Rikkunshito also inhibited cellular migration and invasion status in a dose-dependent manner, and these effects were translated to the enhanced EMT status, although the role of SIRT1 was not determined. Our study revealed a novel function of Rikkunshito in enhancing EMT status of ovarian cancer cells. Therefore, we would like to propose that Rikkunshito may be used as a novel adjunctive therapy in chemotherapy of ovarian cancer because platinum-based chemotherapy frequently used for the treatment of ovarian cancer inevitably impairs appetite.

Impact of Ninjin'Yoeito on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study.

BACKGROUND: Ninjin'yoeito, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment. OBJECTIVES: This prospective exploratory trial evaluates the efficacy of ninjin'yoeito for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. The primary end point was evaluation of fatigue according to Functional Assessment of Chronic Illness Therapy-Fatigue score during 2 courses of nab-paclitaxel plus gemcitabine therapy. Secondary end points included evaluation of dose intensity, appetite loss using numerical rating scale, and peripheral neuropathy using a patient neurotoxicity questionnaire. METHODS: We compared data from this interventional trial with a prior observational trial without administration of ninjin'yoeito with identical definition of end points (UMIN000021758). Thirty patients were required by the study. RESULTS: Threshold mean of Functional Assessment of Chronic Illness Therapy-Fatigue score across 8 weeks during chemotherapy was under 5.3 (P = 0.002). Secondary end points did not reveal any specific patterns in appetite loss or degree of pain. No significant changes in patient neurotoxicity questionnaire concerning sensory/motor disorders were observed, but the mean (SD) incidence of patients with sensory disturbance was higher between the fifth and eighth weeks (8.8 [1.26]) than during the first and fourth weeks (4.8 [0.96]) (P = 0.003). Clinically significant adverse reactions of ninjin'yoeito were not observed. CONCLUSIONS: Ninjin'yoeito may be useful for improving the symptoms of fatigue caused by nab-paclitaxel plus gemcitabine in patients with unresectable pancreatic cancer. UMIN Clinical Trials Registry identifier: UMIN000025606. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Prevalence of the potentially inappropriate Kampo medications to be used with caution among elderly patients taking any prescribed Kampo medications at a single centre in Japan: a retrospective cross-sectional study.

BACKGROUND: Few studies have investigated the prevalence and characteristics of potentially inappropriate Kampo medication use among elderly ambulatory patients taking any prescribed Kampo medications. METHODS: A retrospective cross-sectional study was conducted using electronic medical records. All patients aged 65 years or older who continued visiting internal medicine physicians and were prescribed any Kampo medications from January 2015 to March 2015 were included. The primary outcome was the proportion of patients taking any potentially inappropriate Kampo medications that should be used with caution (hereafter referred to as UWC Kampo medications). The medication appropriateness was evaluated based on the 2015 Japan Geriatrics Society guidelines. RESULTS: Eighty eligible patients were identified. The mean age was 76.7 years, 45 patients (56.2%) were female, the mean Charlson Comorbidity Index was 1.7, the median number of non-Kampo medications used was 5.0, and the median number of Kampo medications used was 1.0. The proportion of patients taking any UWC Kampo medications was 28.8% (95% confidence interval, 18.6 to 38.9%). Medications containing Glycyrrhizae radix for chronic kidney disease or loop diuretics were the most common UWC Kampo medications. Compared with patients who did not take any UWC Kampo medications, patients who did take such medications used aconite compositions more frequently (p = 0.04) and were more likely to have uncontrolled hypertension (p = 0.02) and chronic kidney disease (p <  0.001). In a multivariable analysis, no predictive factors for the use of UWC Kampo medications were identified. CONCLUSIONS: Approximately one-fourth of the elderly patients taking any prescribed Kampo medications took at least one UWC Kampo medication, although the association between UWC Kampo medications and adverse events remains unclear. When physicians prescribe medications containing Glycyrrhizae radix to elderly patients, chronic kidney disease and the use of loop diuretics should be evaluated.

Clinical significance of redox effects of Kampo formulae, a traditional Japanese herbal medicine: comprehensive estimation of multiple antioxidative activities.

To clarify the clinical significance of the redox-controlling effects of Kampo, a traditional Japanese herbal medicine, we determined the scavenging activities of various reactive oxygen species in clinically used Kampo formulae using an electron spin resonance-based technique. Formulae containing Rhei Rhizoma (i.e., mashiningan and daiobotanpito) showed high scavenging activity against the alkoxyl radical, and crude extract quantity was significantly correlated with scavenging activity. Hydroxyl radical scavenging activity was positively correlated with the quantity of Zingiberis Rhizoma. Strong hydroxyl radical scavenging activity was also found in formulae containing both Bupleuri Radix and Scutellariae Radix, a widely used anti-inflammatory combination. Formulae containing a clinically common combination of Scutellariae Radix, Coptidis Rhizoma, and Phellodendri Cortex induced high superoxide scavenging activity. Singlet oxygen scavenging activity was high in formulae containing Bupleuri Radix and Glycyrrhizae Radix. In contrast, formulae containing Rehmanniae Radix showed generally low reactive oxygen species scavenging activities, and the quantity of Rehmanniae Radix was negatively correlated with hydroxyl radical and singlet oxygen scavenging activities. These results indicate that the antioxidative effects of Kampo formulae are not uniform but complexly varied against multiple reactive oxygen species. Some formulae have almost no antioxidant effects but may act as pro-oxidants.

The effects of rikkunshito on body weight loss after esophagectomy.

BACKGROUND: After esophagectomy, esophageal cancer patients suffer from malnutrition, anorexia, and dysfunction of digestion and absorption. Rikkunshito, a traditional Japanese herbal medicine, reportedly attenuates gastrointestinal symptoms and appetite loss after gastrointestinal surgery. We evaluated the clinical effect of rikkunshito and its relationship with ghrelin in esophageal cancer patients after esophagectomy. METHODS: This prospective nonrandomized study included 40 patients with esophageal cancer who underwent esophagectomy at Wakayama Medical University Hospital. They were assigned to either the control group (n = 20, April 2011-January 2012) or the rikkunshito group (n = 20, January 2012-August 2012). Patients in the rikkunshito group received 2.5 g of rikkunshito before every meal for 48 wk beginning 4 wk after surgery. During the 48-week treatment, we assessed body weight loss, nutritional parameters, and quality of life (Functional Assessment of Cancer Therapy-Esophageal scale). The primary end point was the rate of body weight loss in two groups after the 48-week treatments. RESULTS: The rate of body weight loss was significantly less in the rikkunshito group than in the control group (P = 0.016). The acyl ghrelin level after the 48-week treatments was significantly higher in the rikkunshito group (131.7% ± 74.5%) than in the control group (75.6% ± 47.5%, P = 0.039). For the Functional Assessment of Cancer Therapy-Esophageal symptom scale, satisfaction of food consumption in the rikkunshito group was significantly better than in the control group at 52 wk postoperatively (P = 0.031). CONCLUSIONS: For esophageal cancer patients after esophagectomy, rikkunshito is useful for improving body weight loss in connection with an increase in plasma acyl ghrelin levels.

Japanese herbal medicines shosaikoto, inchinkoto, and juzentaihoto inhibit high-fat diet-induced nonalcoholic steatohepatitis in db/db mice.

Few studies have investigated the effects of Japanese herbal medicines on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). To the best of our knowledge, only one study has examined whether high-fat (HF) diet-fed db/db mice are appropriate animal models of NASH. We investigated the effects of four types of Japanese herbal medicines (shosaikoto (TJ-9), inchinkoto (TJ-135), juzentaihoto (TJ-48), and keishibukuryogan (TJ-25)) on hepatic lesions of HF diet-fed db/db mice. Db/db mice were divided into six groups: control diet (control); HF diet (HF); and HF diet supplemented with TJ-9, TJ-135, TJ-48, or TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). Mice were killed after 6 weeks of treatment, and biochemical and pathological analyses were performed. Mice in the HF group consistently developed histopathological features consistent with definite NASH, and marked necroinflammation occurred. Serum alanine aminotransferase levels in the TJ-9, TJ-135, and TJ-48 groups were significantly improved compared with those in the HF group. With regard to liver histology, TJ-9 and TJ-48 significantly improved lobular inflammation, and TJ-135 significantly improved ballooning degeneration. We have shown that HF diet-fed db/db mice are animal models that correctly recapitulate the histopathology of human NASH and that TJ-9, TJ-135, and TJ-48 inhibit necroinflammatory activity in this model.

Successful Administration of Kampo Medicine and Acupuncture Treatment to Improve Erythromelalgia: A Case Report.

Erythromelalgia is a rare disease characterized by a triad of recurrent burning pain, redness with pain, and hot flashes in the legs during attacks. We report the case of a 40-year-old woman who suffered from refractory erythromelalgia for 15 years and was successfully managed with Kampo medicine and acupuncture. Her pain was refractory to seven types of oral medications and intravenous lidocaine injections. Byakkokaninjinto was also administered for concomitant polydipsia in addition to acupuncture, unseiin, orengedokuto, and sokeikakketsuto. Because erythromelalgia has no established treatment, traditional Kampo medicine combined with acupuncture may help improve the quality of life of affected patients.

Suppressive Activity of Boiogito, a Japanese Traditional Kampo Medicine, on Periostin Secretion in Human Fibroblast-Like Synoviocytes In Vitro.

Background Knee osteoarthritis (KOA) is a prevalent degenerative disease that affects the knee joints, particularly among individuals aged over 40 years. It leads to pain, stiffness, and reduced quality of life; affects approximately 300 million individuals worldwide; and is increasing, particularly in developed nations. Although treatments for KOA range from conservative measures to surgical interventions, such as total knee arthroplasty (TKA), the financial burden of TKA in many countries underscores the urgent need for effective conservative therapies. The pathophysiology of KOA involves articular cartilage degeneration, increased subchondral bone turnover, synovitis, and periarticular soft tissue contracture. Abnormal bone turnover, intensified by factors, such as weight gain and knee injury, precedes cartilage degeneration. Synovitis, characterized by inflammation in the synovial tissue, plays a crucial role in perpetuating the disease by triggering a cascade of catabolic and proinflammatory mediators, including cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor-alpha, and IL-13. Periostin, an extracellular matrix protein, is implicated in KOA progression, with its levels increasing with disease severity. Materials & methods In this study, the preventive effect of boiogito (BOT), a traditional herbal medicine, on periostin secretion in human fibroblast-like synoviocytes (hFLS) stimulated by IL-13 was investigated. Synoviocyte Growth Medium and recombinant human IL-13 were used for cell culture and stimulation. BOT was dissolved in phosphate-buffered saline and applied to cell cultures. Periostin secretion and mRNA expression were measured using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Cell viability was assessed using an MTT assay, and signal transducer and activator of transcription factor 6 (STAT6) phosphorylation was examined using Western blotting. Results IL-13 stimulation of hFLS significantly increased periostin secretion, with levels rising above 20 ng/mL after 72 h of stimulation. Pretreatment with BOT dose-dependently suppressed periostin secretion, with doses of 1,000 µg/mL significantly reducing periostin levels. Furthermore, BOT inhibited periostin mRNA expression and STAT6 phosphorylation in IL-13-stimulated hFLS, suggesting its potential in modulating IL-13-mediated inflammatory pathways in KOA. Conclusion This study demonstrated the preventive effect of BOT on periostin secretion in IL-13-stimulated hFLS, highlighting its potential as a therapeutic agent for KOA. By inhibiting periostin production and downstream signaling pathways, BOT may offer a promising conservative treatment option for KOA, addressing the inflammatory cascade implicated in disease progression. Further research is warranted to elucidate the specific herbal components responsible for the therapeutic effects of BOT and to validate its efficacy in clinical settings.

Organizing Pneumonia With Diffuse Alveolar Hemorrhage Induced by the Kampo Medicine Choreito.

Kampo medicine, a traditional Japanese herbal medicine, is covered by the Japanese National Health Insurance and prescribed for various purposes. While relatively safe with few adverse effects, it may potentially cause severe adverse effects, such as lung injury. Herein, we describe the case of a 61-year-old Japanese woman with choreito-induced lung injury that manifested as organizing pneumonia (OP) with diffuse alveolar hemorrhage (DAH). She was referred to our department due to multiple abnormal opacities detected on annual chest radiography. Chest computed tomography (CT) revealed multiple nodules in bilateral lungs. Bloody bronchoalveolar lavage fluid was obtained from the left lingular lobe, appearing nearly normal, while a transbronchial lung biopsy from a subpleural nodule in the left lower lobe was pathologically consistent with OP. The drug lymphocyte stimulation test result was positive for choreito, which the patient had regularly consumed for 6 - 7 months to treat hematuria. Consequently, a diagnosis of choreito-induced OP and DAH was made. Owing to the discontinuation of choreito alone and without the introduction of systemic steroid therapy, the multiple nodules shrank and eventually disappeared on follow-up chest CT. Regardless of the type of crude drug used in Kampo medicine, clinicians must always be careful for potential lung injury, which may present as OP with DAH.

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.

Clinical Experience of Use of Kampo Medicine Shakuyakukanzoto for Muscle Spasms Caused by Tetanus.

Background Tetanus is an infectious disease caused by Clostridium tetani, which produces tetanospasmin. Intensive care using sedatives and muscle relaxants is required for the management of severe tetanus, however, long-term use of those medicines is associated with the occurrence of post-intensive care syndrome (PICS). Shakuyakukanzoto (SKT), which is clinically used for the treatment of pain associated with sudden myospasm widely, is one of Kampo medicines, and some studies showed that they are effective in treating muscle spasms caused by tetanus. The purpose of this study is to evaluate the usefulness of SKT in the management of tetanus patients from the viewpoint of the reduction of sedatives. Methods Patients who were diagnosed with tetanus and were treated in our hospital between January 2006 and December 2022 were included. Patients were divided into two groups, patients treated with SKT and those without SKT, and the background information and clinical courses, especially the reduction of sedatives, were compared between the two groups. Results There were five tetanus patients who were treated with SKT (SKT(+) group) and two tetanus patients without SKT (SKT(-) group), respectively. Intubation and mechanical ventilation were required for the management of generalized seizures in all seven patients, who were admitted to the intensive care unit (ICU). The administration of propofol could be discontinued after an average of 8.6 days (range: 3-22 days) from the initiation of SKT administration. The dosage of propofol was lower in patients who received SKT versus those who did not; midazolam and fentanyl exhibited a similar tendency. The mean durations of ICU and hospital stays for patients treated with or without SKT were almost equal (the mean durations of ICU stay in SKT(+) and SKT(-) groups were 22.6 and 24.0 days, and those of hospital stay in SKT(+) and SKT(-) groups were 35.2 and 36.0 days, respectively). All seven patients were discharged and transferred to another hospital for rehabilitation. Conclusions SKT may be useful in the management of myospasms in patients with tetanus. It may also prevent the occurrence of PICU in patients with tetanus who require intensive care by reducing the use of sedatives and analgesics.

Japanese Herbal Medicine (Kampo) as a Possible Treatment for Ischemia With Non-obstructive Coronary Artery Disease.

Patients presenting with the syndrome of symptoms and signs suggesting ischemic heart disease but found to have no obstructed coronary arteries (INOCA) are increasingly recognized. Although there are non-invasive tests for the diagnosis of INOCA, such as transthoracic Doppler echocardiography, positron emission tomography, and cardiac magnetic resonance imaging to evaluate increased blood flow with adenosine and other agents, the diagnosis of INOCA by coronary angiography with the coronary spasm provocation test and coronary microvascular function evaluation using pressure wires has become the gold standard, but it is not well established in the treatment of INOCA. Despite the lack of objection to lifestyle modification and the use of coronary dilators, mainly calcium-channel blockers, for conditions involving epicardial coronary artery spasm, there is no entirely effective long-term treatment for microvascular spasm or coronary microvascular dysfunction. Although some combinations of drugs have been empirically administered in certain cases, it is difficult to conclude that they are sufficiently effective. Recently, it has been reported that some Japanese herbal medicines (Kampo) have been effective in the treatment of INOCA. In order to increase the knowledge on the treatment of INOCA, this review focuses on the effects of Japanese herbal medicine on INOCA and its presumed mechanisms and problems.

Severe Drug-Induced Liver Injury From Over-the-Counter Medication.

Drug-induced liver injury (DILI) is difficult to diagnose as it presents with a wide variety of clinical manifestations and there is no established specific biomarker. However, clinicians require expertise in diagnosing DILI as it can lead to critical illness, is relatively common, and can be caused by a variety of drugs, herbal medicines, and supplements. A 67-year-old male was admitted to the hospital with a fever, jaundice, and fatigue. Abdominal ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no morphological abnormalities in the hepatobiliary system. On the third day of hospitalization, the liver damage and acute kidney injury progressed, and the patient was transferred to our intensive care unit. To further investigate the cause of multiple organ damage, the patient underwent repeated history taking and additional laboratory testing. In addition to the common causes of hepatic and renal damage, we also tested for rickettsiosis and leptospirosis, as the patient reported partaking regularly in outdoor leisure activities. On day seven of hospitalization, the patient recalled taking over-the-counter herbal flu medications approximately five days prior to admission; therefore, we suspected DILI and performed a drug-induced lymphocyte stimulation test (DLST). The DLST was positive for one drug. As other causes had been ruled out, the patient was diagnosed with severe DILI. The clinical course of the patient was observed with the patient's laboratory data and fever improving spontaneously. This case taught us several important lessons for the investigation of liver injury. Firstly, even with over-the-counter drugs, liver injury can be severe. Secondly, while the DLST is available for investigating DILI, false positives, especially for medicinal herbs, should be noted, and it is necessary to adequately rule out other diseases. Finally, when the cause of liver injury is unclear, patient history taking should be repeated carefully.

Kampo Formula-Pattern Models: The Development of 13 New Clinically Useful Standard Abdominal Pattern Models in the Fukushin Simulator.

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient's physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula-pattern pairings. The present study aims to develop such pairings. Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models. Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (), Dai-joki-To (), Shigyaku-San (), Saiko-ka-ryukotsu-borei-To (), Keishi-bukuryo-Gan (), Hachimi-jio-Gan (), Hange-shashin-To (), Sho-saiko-To (), Hochu-ekki-To (), Sho-kenchu-To (), Toki-shakuyaku-San (), Ninjin-To (), and Dai-kenchu-To (). Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education.

Data of RNA-seq transcriptomes of liver, bone, heart, kidney and blood in klotho mice at a pre-symptomatic state and the effect of a traditional Japanese multi-herbal medicine, juzentaihoto.

We performed RNA-seq analyses of mRNA isolated from five organs, liver, bone, heart, kidney and blood at the pre-symptomatic state of klotho mice with/without administration of a Japanese traditional herbal medicine, juzentaihoto (JTT). Data of differentially expressed genes (DEG) with/without JTT was included. Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. We collected data in which retained-introns were accumulated in a particular set of genes of these organs, and showed that among these retained introns in the liver and bone a subset was recovered to the normal state by the medicine. All of the data present changes of molecular events on the levels of metabolites, proteins and gene expressions observed at the pre- symptomatic state of aging in klotho mice with/without JTT. The research article related to this Data in Brief is published in GENE entitled as "Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese herbal medicine".

Prescription of Choreito, a Japanese Kampo Medicine, with Antimicrobials for Treatment of Acute Cystitis: A Retrospective Cohort Study.

Choreito, a Japanese Kampo medicine, is used to treat Japanese female patients for the quick relief of inflammatory symptoms associated with acute cystitis. We evaluated whether Choreito is effective in reducing antibiotic use and the number of clinic visits for these patients. Females aged 18-49 years who had acute cystitis for the first time, with no history of medical insurance use within 90 days prior to their visit, and no hospitalizations within the 30 days after their first visit were identified from the JMDC Claims Database between April 2018 and March 2021. For the 30 days after their first visit, patients who were given their first antimicrobial prescriptions with or without Choreito were compared regarding (i) the number of clinic visits, (ii) total antimicrobial prescription days, and (iii) the number of antimicrobial prescriptions adjusted for their age, Charlson comorbidity index, and the COVID-19 pandemic period (after April 2020). For the 319 and 8515 patients with or without a Choreito prescription, respectively, multivariable Poisson regression analyses showed that Choreito was significantly associated with a 5% shortening of a patient's total antimicrobial prescription days (Beta, 0.950; p = 0.038), whereas no significant difference was observed in the number of clinic visits and antimicrobial prescriptions (p = 0.624 and p = 0.732, respectively). The prescription of Choreito in combination with antimicrobials was associated with a slight reduction in total antimicrobial use for acute cystitis among females.

A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells.

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists of Zanthoxylum Fructus (Japanese pepper), Zingiberis Siccatum Rhizoma (processed ginger), Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects. Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice. We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon. DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase gene Fut2 and the antimicrobial peptide gene Reg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORγthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation. These findings demonstrate that DKT possesses anti-inflammatory activity, partly via ILC3 function, to maintain the colonic microenvironment. Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

Spontaneous Intracranial Hypotension Manifesting Orthostatic Headache Worsened by Playing the Saxophone and Treated by Japanese Herbal Kampo Medicine Goreisan.

We present a 15-year-old Japanese girl with no previous medical history who presented with a gradually worsening series of orthostatic headaches. We diagnosed spontaneous intracranial hypotension, worsened by playing the saxophone and its Valsalva maneuver effect. She was treated with Japanese herbal Kampo medicine Goreisan 7.5 g/day in three divided doses, and her symptoms gradually improved. Her headache has never recurred for a year when she played the saxophone. Our case's headache may have been further exacerbated by cerebrospinal fluid (CSF) leakage due to CSF pressure increase by Valsalva maneuvers while playing the saxophone. Our case suggested that the Japanese herbal Kampo medicine Goreisan can facilitate the glymphatic system and adjust the CSF pressure appropriately.

Histopathological evaluation of the effectiveness of oral Eppikajutsuto treatment for lymphatic malformation.

BACKGROUND: Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs. METHODS: LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels. RESULTS: Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations. CONCLUSION: TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.