Search Results (114)

Background and Objectives: Japan’s aging population faces growing challenges related to oral frailty, a condition characterized by the decline of oral function associated with physical and nutritional deterioration. Impaired oral function contributes to reduced chewing, swallowing, and saliva secretion, leading to poor appetite and frailty progression. Ninjin’yoeito (NYT), a traditional Kampo formula, has been clinically used to improve systemic weakness and oral symptoms. This study aimed to evaluate the efficacy and safety of NYT in improving oral health among elderly individuals with impaired oral function. Materials and Methods: In this open-label prospective study, patients received NYT daily for 12 weeks. Assessments included oral symptom scores, mucosal moisture, repetitive saliva swallowing tests (RSST), gustatory function by visual analogue scale (VAS), an 11-item oral questionnaire, and immune profiling by flow cytometry. Safety was assessed through hematological and biochemical tests. Results: Symptom scores decreased from 8.27 at baseline to 3.64 at 12 weeks (p = 0.006), while oral condition scores improved from 5.09 to 1.36 (p = 0.006). Mucosal moisture increased (25.1 to 28.1, p = 0.03), and RSST frequency improved (2.18 to 4.55, p = 0.046). Questionnaire scores declined from 5.1 to 2.0 (p < 0.001). VAS-taste was unchanged overall (p = 0.21) but improved in low baseline patients. Laboratory findings showed no adverse changes, with favorable lipid trends. Immune analysis revealed a decline in NKG2D expression (p = 0.02), whereas other activating and inhibitory markers remained stable. Conclusions: NYT was well tolerated and associated with gradual improvements in oral and physical symptoms among elderly individuals with impaired oral function. These findings provide preliminary evidence supporting the feasibility of Kampo-based approaches for maintaining oral health in aging populations and warrant further validation in larger controlled trials. Full article

Since the causes of aging are diverse, anti-aging requires a wide range of strategies. Kampo, a traditional medicine of Japan, which has its roots in traditional Chinese medicine, is generally prepared by combining several natural compounds to produce a multiple pharmacological effect, which is considered useful against aging with various changes. In this study, we evaluated the effects of a medical cosmetic Kampo cream on 14 healthy female subjects aged 31 to 59 years with dry skin and shallow wrinkles at the corners of the eyes using the split-face method. The subjects applied the test cream to only one side of their faces twice a day for 4 weeks. Their wrinkles around the eyes on both sides of their faces were evaluated from photographs taken by expert examiners who were blinded to the subjects. The effects on skin condition were also assessed using a questionnaire given to the subjects. Judgments made by the experts from the photos suggest that the wrinkles on the side of the face where the cream was used were improved, while those on the other side were not. The reduction in wrinkles was more pronounced in elder subjects. This reduction in wrinkles on the test side of the face was also supported by the results of the questionnaire administered to the subjects. In addition to wrinkles, many other aging-related parameters such as skin softness, makeup adhesion, smoothness, tightness after washing the face, and moisture were suggested to be improved with the use of the test cream. These results indicate that the application of the Kampo cream for 4 weeks showed an anti-wrinkle effect and the preservation of the facial skin in a healthy condition, which may be due to the combined effects of the natural ingredients used in Kampo medicine. Full article

Background: This multicenter retrospective study evaluated the long-term outcomes of functional dyspepsia (FD) and factors associated with treatment resistance over a 3-year period after treatment initiation. Methods: A total of 111 patients diagnosed with FD according to the Rome IV criteria and confirmed by upper endoscopy to have no organic disease were retrospectively analyzed. First-line therapy included acid-suppressive drugs, prokinetics, and the Kampo medicine rikkunshito, whereas second-line therapy comprised anxiolytics or antidepressants for refractory cases. Gastrointestinal symptoms, psychological distress, and health-related quality of life were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale (HADS), and Short Form-8. Symptom improvement was evaluated at 1 and 3 years. Results: The improvement rates at 1 and 3 years were 50.5% and 80.2%, respectively. At baseline, the non-improvement group had significantly higher HADS-Depression and GSRS-Abdominal Pain scores (p < 0.05). Multivariate analysis identified HADS-Depression (odds ratio [OR] = 0.676, p = 0.019) and GSRS-Abdominal Pain (OR = 0.461, p = 0.038) as independent predictors of treatment resistance. Conclusions: The present findings indicate that FD often requires prolonged therapy, and baseline depressive symptoms and abdominal pain predict poor long-term outcomes, emphasizing the need for early psychological assessment and integrated management. Full article

Background/Objectives: Juzentaihoto (JTT), a traditional Kampo formula composed of ten medicinal herbs, is widely prescribed in Japan for immune enhancement and general health maintenance. This exploratory, open-label pilot study aimed to evaluate the feasibility and immunomodulatory effects of JTT in cancer patients and to explore its potential mechanisms of action. Methods: Ten cancer patients received oral JTT (7.5 g/day) for 14 days, while healthy volunteers served as a reference group. Peripheral natural killer (NK) cell phenotypes and CD95 expression were analyzed by flow cytometry, and serum Fas ligand (FasL) concentrations were measured by ELISA. Complementary in vitro assays using PBS-extracted, autoclaved JTT were conducted to assess Fas/FasL-mediated apoptosis in Jurkat and primary T cells by flow cytometry and Western blotting for cleaved caspase-8 and -3. Additional experiments with staurosporine (intrinsic apoptosis) and TRAIL in OSC-19 carcinoma cells were performed to determine pathway specificity. Results: In patients, most NK-cell markers showed no statistically significant within-subject changes, although a trend-level increase in NKp46 and a significant reduction in NK-cell CD95 expression (paired p = 0.014) were observed. Between-group differences primarily reflected baseline disparities between cancer patients and healthy controls. In vitro, JTT (50–100 µg/mL) partially attenuated FasL-induced apoptosis and reduced cleaved caspase-3 without affecting cleaved caspase-8, suggesting selective downstream modulation of the extrinsic pathway. Conclusions: Within the limitations of a small, non-randomized cohort without placebo, these findings are hypothesis-generating and indicate that JTT selectively modulates Fas-mediated lymphocyte apoptosis without promoting tumor immune evasion. Further randomized trials and mechanistic studies incorporating co-culture or 3D tumor–immune models are warranted to confirm these observations and identify active constituents. Full article

Oral mucositis (stomatitis) is a painful condition that affects the mouth lining. Kampo medicines (e.g., Hangeshashinto [Chinese name, Ban-Xia-Xie-Xin-Tang], Orento, and Orengedokuto) have been widely used to treat stomatitis, such as gargling with Hangeshashinto. However, the mechanisms by which Kampo medicines work are not widely understood due to their oral administration and the subsequent digestion, absorption, and metabolization of their components. Stomatitis is associated with advanced glycation end-products (AGEs) in patients with lifestyle diseases, and can be induced by both intra- and extracellular AGEs (blood and dietary AGEs). Various natural products inhibit intracellular AGE generation and suppress cytotoxicity, such as inflammation caused by extracellular AGEs. This review summarizes 19 natural products identified in the Hangeshashinto water extract and 16 natural products identified in the crude drug extract. The data show that several natural products, such as glycyrrhizin, baicalin, 6-shogaol, quercetin, epigallocatechin-3-galate, and genistein, inhibit intracellular AGEs and suppress extracellular AGE inflammation. Furthermore, several natural products in the Hangeshashito water extract can suppress cytotoxicity in stomatitis. Full article

Background: Ephedra przewalskii Stapf stems are a traditional Mongolian medicine commonly used to treat infectious diseases. Previous in vitro experiments have shown that the extract powder derived from its stems possesses antiviral activity. However, the active compounds responsible for this activity in E. przewalskii Stapf have not yet been identified or evaluated. This study aimed to identify the active components in E. przewalskii that exhibit antiviral effects against SARS-CoV-2 in vitro and validate their antiviral activity. Methods: E. przewalskii stem extracts were subjected to high-performance liquid chromatography with varying methanol ratios in the mobile phase to obtain fractions with different polarities. Antiviral activity was assessed by infecting VeroE6/TMPRSS2 cells with the SARS-CoV-2 Delta strain and treating them with the obtained fractions. Infectious titers were measured using the 50% tissue culture infective dose (TCID₅₀) method, and half-maximal inhibitory concentration (IC₅₀) values were calculated for each fraction. The active components in the two fractions with the highest antiviral activity were identified and structurally characterized by nuclear magnetic resonance analysis. The antiviral activity of these compounds was confirmed by adding them to SARS-CoV-2-infected cells and measuring their infectious titers using the TCID₅₀ method. The IC₅₀ values were also calculated. Viral-particle inactivation assays were conducted by mixing the extracts with SARS-CoV-2 and measuring infectious titers. Results: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin were isolated from E. przewalskii. These compounds exhibited significant antiviral activity against SARS-CoV-2 but demonstrated minimal direct virucidal effects. Conclusion: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin exhibit antiviral activity against SARS-CoV-2 in infected cells. Full article

The capitula of Chrysanthemum indicum Linné or C. morifolium Ramatuelle (Kikuka in Japanese) are included in several formulae of Kampo medicines (traditional Japanese medicines), such as Chotosan, which is used for headache and dizziness. Luteolin, the principal constituent of C. indicum, has antioxidant and anti-inflammatory activities. However, the effects of other flavonoids on this crude drug have not yet been thoroughly investigated. To evaluate and compare anti-inflammatory effects, we used primary cultured rat hepatocytes, which produce proinflammatory mediators, such as nitric oxide (NO) and proinflammatory cytokines, in response to interleukin (IL)-1β. Eight derivatives of 5,7-dihydroxyflavone were purified and identified in the ethyl acetate-soluble fraction of a C. indicum capitulum extract: luteolin (Compound 1), apigenin (2), diosmetin (3), 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone (4), acacetin (5), eupatilin (6), jaceosidin (7), and 6-methoxytricin (8). Luteolin is the most abundant compound in this fraction. All compounds significantly suppressed NO production in hepatocytes, with apigenin and acacetin showing the greatest efficacy. The comparison of the IC₅₀ values of the inhibition of NO production suggests that substitutions by hydroxyl and methoxy groups at the C-3′ and C-4′ positions of 5,7-dihydroxyflavone may be at least essential for the suppression of NO production. In hepatocytes, acacetin and luteolin decreased the levels of mRNAs encoding inducible nitric oxide synthase (iNOS), proinflammatory cytokines, including tumor necrosis factor, IL-6, and type 1 IL-1 receptor, which regulates inflammatory responses. Based on the comparison of the IC₅₀ values and the content, luteolin, jaceosidin, and diosmetin may be responsible for the anti-inflammatory effects of C. indicum capitula. Full article

‘Blood stasis’ (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (血瘀). Similar concepts exist in Traditional Korean Medicine (‘Eohyul’) and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down (‘stasis’) of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke. Full article

Ephedrine alkaloids-free Ephedra Herb extract (EFE) was developed to reduce the adverse effects of Ephedra Herb, a constituent drug in Kampo medicines. It is produced by decocting Ephedra Herb with hot water and excluding the ephedrine alkaloids. EFE has analgesic and anti-cancer effects and inhibits respiratory viruses in vitro. To assess the pharmacological action of EFE in vivo, we evaluated its effect on the replication of murine hepatitis virus (MHV), a coronavirus that causes hepatitis, pneumonia, and severe acute respiratory syndrome-like symptoms, within infected mice. On Day 0, MHV was inoculated intranasally into female BALB/C mice, and EFE was orally administered once/day at 350–700 mg/kg (n = 10/group) starting 1 h after inoculation until Day 5. Through a plaque assay, MHV was detected on Day 5 in the lung and liver in all inoculated mice, but the titer was significantly lower in the EFE groups as compared with untreated control mice. Although not statistically significant, the clinical score for respiratory irregularity tended to be lower in the EFE treatment groups. In conclusion, EFE inhibits MHV replication in an in vivo mouse model of human coronavirus infection and exerts pharmacological action in the lung and liver. Full article

Osteoporosis can increase the risk of fracture in elderly patients, and insufficient control affects quality of life. Rikkunshi-To (RKT) has been prescribed for elderly patients to improve gastrointestinal function. We postulated that RKT has preventive potential for the development of osteoporosis. Thus, we developed a simple method to evaluate osteoporosis using a continuous series of X-ray images of femurs in mice, and investigated the effects of RKT on the development of osteoporosis in these mice. Male senescence-accelerated mouse strain P6 (SAMP6) mice, a model of senile osteoporosis in humans, were fed diets with or without RKT (1%). We collected X-ray images of the whole body of each mouse weekly and measured the ratio of cortical thickness of the femur (C/F index). The C/F index in SAMP6 mice fed the normal diet was increased between 50 and 80 days old, but it was significantly decreased after 120 days old. On the other hand, the C/F index in SAMP6 mice fed the RKT diet was increased between 50 and 80 days old; however, it remained unchanged throughout the experimental period. We also confirmed that the C/F index in SAMP6 mice fed the RKT diet suddenly decreased on the replacement of the RKT diet with a normal diet, suggesting that we can collect data related to a series of continuous changes in bone mass, and that RKT is useful for the prevention of osteoporosis. Full article

Tryptase, which is abundant in human mast cells and is involved in allergic inflammations such as asthma, is a serine protease. We isolated a tryptase inhibitor, procyanidin B8 3,3′-di-O-gallate (PB8GG’), a tannin, from the methanol extract of rhubarb (RHEI RHIDOMA), which is a traditional Chinese medicine (Kampo medicine in Japan). Since it did not inhibit another serine protease trypsin, PB8GG’ specifically inhibited tryptase. A standard kinetic analysis of the inhibitory fashion of PB8GG’ against tryptase suggested that PB8GG’ inhibited tryptase in an allosteric manner. We searched for other tannins like PB8GG’ expected to bind tryptase using AutoDock vina. Two ellagitannins, carpinins B and E, isolated from young leaves of Carpinus japonica were selected as candidates of tryptase inhibitors. Carpinins B and E themselves had almost no inhibitory activity against tryptase but enhanced the inhibitory activity of PB8GG’ against tryptase. This is an example that shows that a combination of an allosteric inhibitor with other compounds that bind but have no inhibitory activity can be used to develop a clinically useful combinatorial enzyme inhibitor. Full article

Several Ephedra Herb-containing Kampo medicines are common initial treatments for various infections; however, the ephedrine alkaloids in Ephedra Herb can cause side effects by stimulating adrenergic receptors. Accordingly, an ephedrine alkaloids-free Ephedra Herb Extract (EFE) has been developed. This study aimed to evaluate whether EFE can be used effectively and safely in patients with mild coronavirus disease 2019 (COVID-19). We randomized patients with mild COVID-19 to receive EFE equivalent to 6 g of Ephedra Herb per day or a placebo for 14 days. The primary efficacy endpoint was the non-aggravation rate up to Day 15. We allocated 41 and 40 patients to the EFE and placebo groups, respectively. All participants were included in the mITT and safety analysis populations [male ratio, mean age: 31.7%, 42.0 years (EFE); 17.5%, 43.2 years (placebo)]. The non-aggravation rate up to Day 15 for the primary endpoint was 100.0% and 94.6% in the EFE and placebo group, respectively, with no between-group difference. The number of days to the improvement in nausea symptoms was significantly shorter in the EFE group. One patient in the placebo group discontinued the trial due to a side effect. Although EFE demonstrated safety in patients with mild COVID-19, it did not show superior efficacy compared to placebo for symptoms other than nausea. Full article

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients’ fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5–8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. Full article

Centella asiatica, a traditional medicinal plant, possesses potent antioxidant activity and may therefore prevent cellular aging and exert antiapoptotic effects. However, these effects remain to be fully elucidated. This study aimed to investigate the protective effects of C. asiatica extract against cellular senescence and apoptosis caused by hydrogen peroxide (H₂O₂)-induced oxidative stress in human epidermal keratinocytes (HaCaT cells). To evaluate the effects of H₂O₂ and C. asiatica on HaCaT cells, we measured cell viability as a marker of cell death; reactive oxygen species (ROS), radical scavenging, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities as markers of oxidative stress; senescence-associated β-galactosidase (SA-β-gal) activity as a marker of cellular senescence; and caspase-3/9 activities and apoptotic cells as markers of apoptosis. H₂O₂ induced cell death (decreased cell viability), oxidative stress (increased ROS activity, decreased radical scavenging, SOD, GPx, and catalase activities), cellular senescence (increased SA-β-gal activity), and apoptosis (increased early/late apoptotic cells and increased caspase-3/9 activities). C. asiatica significantly decreased all markers of H₂O₂-induced cell death, oxidative stress, cellular senescence, and apoptosis, suggesting its ability to prevent cellular senescence and apoptosis through its antioxidant activity. This mechanism of action may contribute to the prevention and improvement of skin aging. Full article

The adverse effects of anticancer drugs significantly impact the quality of life of patients undergoing chemotherapy, necessitating evidence-based supportive therapies. In Japan, Kampo medicines, traditional Japanese herbal therapies used for relief of various symptoms, have been widely used as complementary and alternative treatments for cancer, despite limited evidence regarding their efficacy and safety. Thus, we investigated the actual use of Kampo medicines as supportive care in patients undergoing anticancer drug treatment and evaluated the trends in prescription according to year. We analyzed 89,141 cancer drug therapy cases registered in the Japan Medical Data Center database between April 2014 and July 2022, excluding those with a history of Kampo medicine prescriptions before the first prescription of antineoplastic drugs. We assessed the trends in prescription according to sex, age group (<50, 50–74, and ≥75 years), and cancer type subgroup using the Cochran–Armitage trend test. Approximately 23.7% of patients were prescribed Kampo medicines during anticancer drug treatment. Since 2014, a decrease in the prescription of Kampo medicines during anticancer treatment has been observed regardless of sex, age, or cancer type. These findings suggest that recent negative reports on the efficacy and safety of Kampo medicines in cancer care may have influenced this trend. Full article