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1.
Complement Ther Med ; 45: 7-13, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331585

RESUMO

OBJECTIVES: In Kampo medicine, a traditional medicine pattern(TM1) refers to the complete clinical presentation of the patient at a given moment in time. Candidate herbal formulas are chosen for a chief complaint, and an appropriate formula is determined on the basis of the pattern(TM1) diagnosis. In this study, we demonstrated the importance of accompanying symptoms in diagnosing traditional medicine patterns(TM1). DESIGN: Single centre observational study. SETTING: We analysed data from 524 new patients with a hypersensitivity to cold sensation as their primary diagnosis (mean age 51.6 ± 17.8 years; female ratio 82.1%) who visited the Keio University Hospital Kampo Clinic between 2008 and 2013. MAIN OUTCOME MEASURES: Accompanying symptoms were recorded on the browser-based e-questionnaire system, which contained 128 items. The Japan Society for Oriental Medicine's board certified Kampo specialists diagnosed the traditional medicine patterns(TM1). RESULTS: When participants were classified according to the origin of their cold sensation, there were no differences in their traditional medicine patterns. In contrast, when patients were classified based on the number of accompanying symptoms, a significant difference in the patterns was identified. An increasing number of accompanying symptoms was associated with more frequent qi stagnation and blood stasis pattern(TM1). Patients with a qi stagnation pattern had higher rates of depression and insomnia. In contrast, patients with a blood stasis pattern(TM1), had higher rates of acne, body stiffness, and menstrual abnormality. CONCLUSIONS: Qi stagnation and blood stasis patterns(TM1) are related to a number of different accompanying symptoms in the patients with hypersensitivity to cold sensation.


Assuntos
Sensação/fisiologia , Temperatura Baixa , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Japão , Masculino , Medicina Kampo/métodos , Pessoa de Meia-Idade , Qi , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Inquéritos e Questionários
2.
J Nat Med ; 73(3): 661-666, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028662

RESUMO

To evaluate the safety and efficacy of Glycyrrhiza uralensis root produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems, we investigated the pharmacokinetics of a major metabolite of glycyrrhizin (GL), glycyrrhetinic acid (GA). Hot water extracts obtained from the roots of the artificial hydroponic-field hybrid cultivated Glycyrrhiza uralensis were orally administered at a dose of 100 mg/kg as GL in mice and, compared with a commercial crude drug, Glycyrrhizae Radix. The temporal changes in serum GA concentration was found to depend on the GL concentration of the hot-water extracts. When hot-water extracts containing relatively high GL were administered, bimodal peaks appeared. In contrast, a broad single peak was detected when a hot-water extract containing relatively low GL content was administered. These tendencies in the serum GA concentration time course were observed for all samples, regardless of their derivation. Moreover, we compared the pharmacokinetic parameters and found that the Cmax and AUC0-48 values after oral administration of the extracts from Glycyrrhiza uralensis roots produced by the artificial cultivation system are within the range of variation for the commercial crude drugs. These results suggest the possibility that roots of Glycyrrhiza uralensis cultivated by the artificial hydroponic-field hybrid cultivation system can be used in addition to currently available commercial crude drugs produced from wild plant resources.


Assuntos
Ácido Glicirretínico/química , Glycyrrhiza uralensis/química , Hidroponia/métodos , Medicina Kampo/métodos , Extratos Vegetais/química , Raízes de Plantas/química , Animais , Feminino , Camundongos , Raízes de Plantas/metabolismo
3.
J Ethnopharmacol ; 236: 231-239, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30862522

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kami-shoyo-san (KSS) is a Kampo formula used clinically for menopause-related symptoms in Japan. However, the effect of KSS on autism spectrum disorder (ASD), a developmental disorder with a higher prevalence in males than in females, has not been reported yet. AIM OF THE STUDY: It is accepted generally that dysfunction in the GABAergic system is associated with pathogenesis of ASD. In our previous study, a decrease in brain allopregnanolone (ALLO), a positive allosteric GABAA receptor modulator, induced ASD-like symptoms such as impaired sociability-related performance and increased repetitive self-grooming behavior in male mice, and that KSS ameliorated these behavioral abnormalities via GABAA receptor- and dopamine D1 receptor-mediated mechanisms. In this study, to better understand a gender difference in the prevalence of ASD, we examined whether dissection of ovary (OVX), a major organ secreting progesterone in females, causes ASD-like behaviors in a manner dependent on brain ALLO levels, and if so, how KSS affects the behaviors. MATERIALS AND METHODS: Six-week-old ICR female mice received ovariectomy, and KSS (74 mg/kg and 222 mg/kg, p.o.) were treated before 1 h starting each behavioral test. The sociability, social anxiety-like behavior, and self-grooming behavior were analyzed by the resident-intruder test, mirror chamber test, and open field test, respectively. After finishing the behavioral experiment, the ALLO content in the brain was measured by ELISA. Furthermore, we examined the effects of OVX on the neuro-signaling pathways in the prefrontal cortex and striatum by Western blotting. RESULTS: The results revealed that OVX induced sociability deficits and social anxiety-related behaviors, but not repetitive self-grooming behavior, and that these behavioral changes were accompanied not only by a decrease of brain ALLO levels, but also by impairment of CREB- and CaMKIIα-mediated neuro-signaling in the prefrontal cortex. Moreover, the administration of KSS had no effect on the brain ALLO level, but significantly ameliorated the OVX-induced behavioral and neurochemical changes via facilitation of GABAA receptor and dopamine D1 receptor-mediated neurotransmission. CONCLUSIONS: These findings suggest that a decrease in gonadal hormone-derived ALLO plays a major role in ASD-like behaviors in female mice and that KSS is beneficial for the treatment of ASD in females.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Kampo/métodos , Comportamento Social , Animais , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/química , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ovariectomia , Córtex Pré-Frontal/química , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Pregnanolona/análise , Pregnanolona/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de GABA-A/metabolismo , Fatores Sexuais , Resultado do Tratamento
4.
J Nat Med ; 73(3): 497-503, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30790129

RESUMO

The capitula of Chrysanthemum morifolium and C. indicum are used to prepare Chrysanthemi Flos in traditional Japanese Kampo medicine. In our previous study, we reported on the agonistic effect of methanol extract of C. indicum capitulum on peroxisome proliferator-activated receptor (PPAR)-γ. We further isolated (E)-tonghaosu from C. indicum capitulum as one of the active ingredients. In the present study, we aimed to evaluate the PPAR-γ agonistic activity of a methanol extract of C. morifolium capitulum (MCM) in which (E)-tonghaosu could not be detected. MCM exhibited PPAR-γ agonistic activity in a concentration-dependent manner, and at a dose of 100 µg/ml, it showed similar activity to pioglitazone (30 µM), a standard PPAR-γ agonist. Through activity-guided fractionation, we isolated two geometric isomers, (E)- (1) and (Z)-B-ring-homo-tonghaosu (2), as the active ingredients of MCM. Both compounds exerted concentration-dependent PPAR-γ agonistic effects, and 1 had higher activity than 2. At 1.4 µM, 1 had similar activity to pioglitazone (30 µM), which was achieved by 2 at a concentration of 140 µM. Thus, 1 has the potential to become a lead compound for the drug discovery of PPAR-γ agonists. We compared the activities and the contents of (E)-, (Z)-tonghaosu, 1, and 2 among 13 commercial samples of Chrysanthemi Flos, including those derived from both C. morifolium and C. indicum. Their PPAR-γ agonistic activities were not related to the contents of these compounds. 1 and 2 were detected in the samples derived from both species but (E)- and (Z)-tonghaosu were not detected in the samples derived from C. morifolium; hence (E)- and (Z)-tonghaosu can serve as marker compounds to identify the capitula of C. indicum in Chrysanthemi Flos samples.


Assuntos
Alquinos/química , Chrysanthemum/química , Flores/química , Medicina Kampo/métodos , PPAR gama/uso terapêutico , Extratos Vegetais/química , Compostos de Espiro/química , Animais , PPAR gama/farmacologia
5.
J Nat Med ; 73(3): 468-479, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30739283

RESUMO

The Kampo medicine yokukansan (YKS) has a wide variety of properties such as anxiolytic, anti-inflammatory and analgesic effects, and is also thought to regulate tumor suppression. In this study, we investigated the anti-tumor effect of YKS. We used Lewis lung carcinoma (LLC)-bearing mice that were fed food pellets containing YKS and then performed a fecal microbiota analysis, a microarray analysis for microRNAs (miRNAs) and an in vitro anti-tumor assay. The fecal microbiota analysis revealed that treatment with YKS partly reversed changes in the microbiota composition due to LLC implantation. Furthermore, a miRNA array analysis using blood serum showed that treatment with YKS restored the levels of miR-133a-3p/133b-3p, miR-1a-3p and miR-342-3p following LLC implantation to normal levels. A TargetScan analysis revealed that the epidermal growth factor receptor 1 signaling pathway is one of the major target pathways for these miRNAs. Furthermore, treatment with YKS restored the levels of miR-200b-3p and miR-200c-3p, a recognized mediator of cancer progression and controller of emotion, in the hypothalamus of mice bearing LLC. An in vitro assay revealed that a mixture of pachymic acid, saikosaponins a and d and isoliquiritigenin, which are all contained in YKS, exerted direct and additive anti-tumor effects. The present findings constitute novel evidence that YKS may exert an anti-tumor effect by reversing changes in the fecal microbiota and miRNAs circulating in the blood serum and hypothalamus, and the compounds found in YKS could have direct and additive anti-tumor effects.


Assuntos
Medicina Kampo/métodos , Neoplasias/tratamento farmacológico , Animais , Ansiolíticos/farmacologia , Humanos , Masculino , Camundongos
6.
J Dermatol ; 46(4): 308-313, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803018

RESUMO

Antimicrobial agents have been used for eradication of Cutibacterium (formerly Propionibacterium) acnes that is an exacerbation factor of the skin disease acne vulgaris. However, the use of antibiotics is associated with an increased risk of promoting the emergence of resistant bacteria and leading to skin dysbiosis. Traditional Japanese Kampo medicines, such as Keigairengyoto, are used to treat acne. However, there is incomplete understanding regarding their functional mechanism in treatment of acne. In this study, we examined the antimicrobial and anti-lipase activity of the Kampo medicines used empirically for acne treatment. Three oral medicines, Keigairengyoto, Seijoboufuto and Jumihaidokuto, were found to inhibit the growth of C. acnes and decrease the lipase activity. Especially, Keigairengyoto caused remarkable decrease of bacterial lipase activity. Furthermore, topical medicines such as Shiunko and Chuoko significantly decreased the lipase activity in a dose-dependent manner, without inhibiting C. acnes growth. The topical medicines were found to inhibit the expression of gehA, which codes for extracellular lipase. Our results indicate that Shiunko and Chuoko have potential as effective acne therapeutic agents, especially because they do not promote the emergence of antimicrobial-resistant bacteria and skin dysbiosis.


Assuntos
Acne Vulgar/tratamento farmacológico , Anti-Infecciosos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/microbiologia , Administração Tópica , Anti-Infecciosos/uso terapêutico , Proteínas de Bactérias/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Lipase/metabolismo , Medicina Kampo/métodos , Testes de Sensibilidade Microbiana , Propionibacterium acnes/isolamento & purificação , Propionibacterium acnes/metabolismo
7.
J Nat Med ; 73(1): 163-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30374696

RESUMO

Oxidative stress due to the overproduction of reactive oxygen species plays an important role in the pathogenesis of various diseases. In the present study, we comprehensively evaluated the antioxidant activities of 147 oral formulations of Japanese traditional herbal medicines (Kampo medicines), representing the entire panel of oral Kampo medicines listed in the Japanese National Health Insurance Drug List, using in vitro radical scavenging assays, including the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay, the superoxide anion scavenging activity assay, and the oxygen radical absorption capacity assay. Three of the formulations tested, namely, Tsudosan, Daisaikoto, and Masiningan, showed the most potent in vitro antioxidant activities and were selected for further investigation of their intracellular and in vivo antioxidant effects. The results of the 2',7'-dichlorodihydrofluorescin diacetate assay demonstrated that all three Kampo medicines significantly inhibited hydrogen peroxide-induced oxidative stress in human hepatocellular liver carcinoma HepG2 cells. In addition, Tsudosan significantly increased the serum biological antioxidant potential values when orally administrated to mice, indicating that it also had in vivo antioxidant activity. The potent antioxidant activity of Tsudosan may be one of the mechanisms closely correlated to its clinical usage against blood stasis.


Assuntos
Antioxidantes/uso terapêutico , Medicina Kampo/métodos , Plantas Medicinais/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Humanos , Japão , Espécies Reativas de Oxigênio
8.
J Pharm Biomed Anal ; 164: 119-127, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30368117

RESUMO

Traditional herbal medicine (THM) consists of a vast number of compounds that exert pharmacological effects throughout the body. Comprehensive phenotyping analysis using omics is essential for understanding the nature of THM in detail. We previously reported that the Japanese Kampo medicine maoto ameliorated flu-like symptoms in a rat infection model and dynamically changed plasma metabolites as indicated by metabolome analysis. The aim of this study was to apply wide-targeted plasma metabolomics with quantitative analysis of maoto compounds in a human clinical trial to evaluate the effect of maoto on plasma metabolites. Four healthy human subjects were recruited. Plasma samples were collected before and 0.25, 0.5, 1, 2, 4 and 8 h after maoto treatment. Wide-targeted metabolomics and quantitative analysis of the main chemical constituents of maoto were then performed. Plasma metabolome analysis revealed that maoto administration decreased essential amino acids including branched-chain amino acids (BCAAs) and increased various kinds of ω-3 fatty acids including eicosapentaenoic acid and docosahexaenoic acid, consistent with previous studies in rats. Fifteen of the major compounds in maoto were identified in the systemic circulation. Finally, the correlation between endogenous metabolites and maoto compounds in plasma was analyzed and the results indicated that the decrease in plasma BCAAs might be caused by ephedrines present in maoto. The present study demonstrated that plasma metabolomic studies of endogenous and exogenous metabolites are useful for elucidating the mechanism of action of THM.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Medicina Kampo/métodos , Metabolômica/métodos , Adulto , Aminoácidos de Cadeia Ramificada/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Ácidos Graxos Ômega-3/sangue , Voluntários Saudáveis , Humanos , Masculino , Metaboloma , Metabolômica/instrumentação
9.
Sci Rep ; 8(1): 11216, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-30046160

RESUMO

Natural medicines (i.e., herbal medicines, traditional formulas) are useful for treatment of multifactorial and chronic diseases. Here, we present KampoDB ( http://wakanmoview.inm.u-toyama.ac.jp/kampo/ ), a novel platform for the analysis of natural medicines, which provides various useful scientific resources on Japanese traditional formulas Kampo medicines, constituent herbal drugs, constituent compounds, and target proteins of these constituent compounds. Potential target proteins of these constituent compounds were predicted by docking simulations and machine learning methods based on large-scale omics data (e.g., genome, proteome, metabolome, interactome). The current version of KampoDB contains 42 Kampo medicines, 54 crude drugs, 1230 constituent compounds, 460 known target proteins, and 1369 potential target proteins, and has functional annotations for biological pathways and molecular functions. KampoDB is useful for mode-of-action analysis of natural medicines and prediction of new indications for a wide range of diseases.


Assuntos
Bases de Dados Factuais , Medicina Kampo/métodos , Medicina Tradicional/tendências , Fitoterapia/tendências , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Genoma , Humanos , Medicina Kampo/tendências , Proteoma/genética
10.
Tokai J Exp Clin Med ; 43(2): 68-73, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-29961935

RESUMO

OBJECTIVES: Japanese traditional (Kampo) medicine has its own theories that are quite different from those of Western medicine. For many students and medical doctors, mastering it is a painstaking task. We examined the similarities in clinical reasoning between Western and Kampo medicine, and developed an easy-to-understand method to teach Kampo theories enabling physicians to make accurate diagnoses and choose suitable Kampo formulae. METHODS: We developed a teaching method for Kampo medicine along clinical reasoning for beginners and evaluate its availability and effectiveness in an actual team-based learning class. RESULTS: A Kampo diagnostic procedure similar to that in Western medicine was developed. In this method, some Kampo formulae, are chosen according to the chief complaint, concomitant symptoms, characteristics, and distribution and exacerbation factors. Subsequently, from a point of view of the chosen Kampo formulae, patients' signs and symptoms are matched to find the most suitable formula. Students chose the same suitable formula among 6 groups and gained confidence to choose the correct Kampo formulae. CONCLUSIONS: A new Kampo educational method was developed that raises students' and physicians' confidence in making diagnoses and prescribing Kampo medicines.


Assuntos
Educação Médica/métodos , Medicina Kampo , Ensino , Competência Clínica , Compreensão , Técnicas e Procedimentos Diagnósticos , Composição de Medicamentos , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Cefaleia/etiologia , Humanos , Aprendizagem , Masculino , Medicina Kampo/métodos , Pessoa de Meia-Idade , Médicos , Prescrições , Estudantes de Medicina , Inquéritos e Questionários
11.
J Nat Med ; 72(4): 897-904, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29797179

RESUMO

In modern medical care in which Kampo and Western drugs are often combined, it is extremely important to clarify drug-drug interaction (DDI) to ensure safety and efficacy. However, there is little evidence of DDI in Kampo medicines. Therefore, as part of our studies to clarify the DDI risk for Kampo medicines, we evaluated the effects of five Kampo medicines [yokukansan (YKS), rikkunshito (RKT), shakuyakukanzoto (SKT), hangeshashinto (HST), and goshajinkigan (GJG)] that are widely used in Japan, on drug transporter P-glycoprotein (P-gp) using a Caco-2 permeability assay. These Kampo medicines inhibited the P-gp transport of digoxin through a Caco-2 cell monolayer. The IC50 values were 1.94-10.80 mg/ml. Of the five Kampo medicines, YKS showed the strongest inhibition (IC50 = 1.94 mg/ml), which was attributed to Uncariae Uncis Cum Ramulus. Unfortunately, we could not find the active ingredients responsible for its action. Finally, the Igut/IC50 values for the five Kampo medicines were calculated, and the DDI risk was objectively evaluated according to the criteria in the DDI guidance issued by the Japanese Ministry of Health, Labor, and Welfare and the US Food and Drug Administration. The Igut/IC50 values for the five Kampo medicines were ≤3.4. As these values were <10, they were evaluated as having a weak P-gp inhibitory effect that does not require further verification in humans, suggesting that the DDI risk due to P-gp inhibition for these Kampo medicines is low. The results should provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Células CACO-2/metabolismo , Medicina Kampo/métodos , Interações Medicamentosas , Humanos , Permeabilidade
12.
J Nat Med ; 72(3): 694-705, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29569221

RESUMO

Constipation is a common symptom frequently compromising the quality of daily life. Several mechanistically different drugs have been used to mitigate constipation, including Japanese herbal (Kampo) medicines. However, the mechanisms of their actions are often not well understood. Here we aimed to investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a Kampo medicine empirically prescribed for chronic constipation. Cl- channel activity was measured by the patch-clamp method in human cystic fibrosis transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human intestinal Caco-2 cells. cAMP was measured by a luciferase-based assay. Cell volume change was measured by a particle-sizing and particle-counting analyzer and video-microscopic measurement. In both CFTR-expressing HEK293T and Caco-2 cells, JCT dose-dependently induced whole-cell currents showing typical biophysical and pharmacological features of CFTR. Robust expression of CFTR was confirmed by RT-PCR and Western blotting in Caco-2 cells. Luciferase-based measurement revealed that JCT increases intracellular cAMP levels. Administration of the adenylate cyclase inhibitor SQ22536 or CFTR inhibitor-172, or treatment with small interfering RNAs (siRNA) targeting CFTR, abolished JCT-induced whole-cell currents, suggesting that elevated intracellular cAMP by JCT causes activation of CFTR in Caco-2 cells. Finally, blockade of CFTR activity by CFTR inhibitor-172 or siRNA-knockdown of CFTR or application of SQ22536 markedly reduced the degree of cell volume decrease induced by JCT. JCT can induce a Cl- efflux through the CFTR channel to promote water secretion, and this effect is likely mediated by increased cAMP production.


Assuntos
Cloretos/metabolismo , Constipação Intestinal/tratamento farmacológico , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Intestinos/efeitos dos fármacos , Medicina Kampo/métodos , Animais , Células CACO-2 , Constipação Intestinal/metabolismo , Células HEK293 , Humanos , Mucosa Intestinal/metabolismo , Intestinos/patologia , Transfecção
13.
J Nat Med ; 72(1): 192-201, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28983786

RESUMO

The Japanese Pharmacopoeia defines byakujutsu (Atractylodes rhizome) as the rhizome of Atractylodes japonica or A. macrocephala and sojutsu (Atractylodes lancea rhizome) as the rhizome of A. lancea, A. chinensis, or their interspecific hybrids. Because their pharmaceutical uses differ in traditional Japanese Kampo medicine and traditional Chinese medicine, with less apparent scientific evidence, we compared the pharmacological properties between byakujutsu and sojutsu. Crude drug specimens of byakujutsu (n = 40) and sojutsu (n = 49) obtained in markets were identified by their species using DNA profiling. Their pharmacological properties were evaluated by the inhibitory effect of a MeOH extract of the samples on nitric oxide (NO) production by lipopolysaccharide-stimulated murine macrophage-like RAW264.7 cells and by the inducing effect of boiling water extract of the samples on granulocyte-colony stimulating factor (G-CSF) secretion from murine normal colonic epithelial MCE301 cells. We authenticated A. macrocephala (n = 8), A. japonica (n = 35), and the hybrid between A. macrocephala and A. japonica (n = 1), and they were used as byakujutsu. We authenticated A. chinensis (n = 25), A. lancea (n = 14), and the hybrid between A. chinensis and A. lancea (n = 6), and they were used as sojutsu. The inhibitory effects of byakujutsu on NO production were significantly higher than those of sojutsu (P < 0.05). This activity of A. japonica rhizome was significantly higher than that of A. macrocephala rhizome and A. lancea rhizome (P < 0.01). The activity of A. chinensis rhizome was significantly higher than that of A. lancea rhizome (P < 0.05). The extract of A. japonica rhizome significantly induced G-CSF secretion from MCE301 cells in a concentration-dependent manner. These effects of byakujutsu samples were not significantly different from those of sojutsu samples. A. japonica rhizome had significantly higher activity than A. macrocephala rhizome; however, there were no statistically significant differences among A. japonica, A. chinensis, and A. lancea. The pharmacological differences of byakujutsu and sojutsu may not be large among highly variated crude drug samples with average values, and quality control with the identification of the original plant species of byakujutsu and sojutsu may guarantee their pharmacological properties.


Assuntos
Anti-Inflamatórios/uso terapêutico , Atractylodes/química , Medicamentos de Ervas Chinesas/química , Medicina Kampo/métodos , Rizoma/química , Animais , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos
14.
J Nat Med ; 72(1): 118-126, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28825180

RESUMO

In vitro screening methods using cultured Neuro2a cells to examine the activation (phosphorylation) of extracellular signal-regulated kinase (ERK) 1/2 and promotion of neurite outgrowth revealed that the extracts of 5 Kampo (Japanese traditional) formulations have potential as medicines for the treatment of behavioral abnormalities. Since sansoninto (SAT) extract exerted stronger effects than the other candidates tested, we investigated whether its oral administration ameliorates the pathologies of some mouse models of behavioral impairments. The results obtained suggested that SAT extract exerted anti-depression-like effects in the forced swim test, which may be mediated by the up-regulated expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. They may also be mediated by the enhanced phosphorylation of the cAMP response element-binding protein (CREB) via the mitogen-activated protein kinase (MAPK) cascade and Ca2+/calmodulin-dependent protein kinase II (CaMK II) cascade, a downstream signaling cascade of the N-methyl-D-aspartate (NMDA) receptor. These results indicate that the extract of SAT has potential as a new remedial medicine in the treatment of depression-like behavior.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Medicina Kampo/métodos , Animais , Japão , Masculino , Camundongos
15.
Trials ; 18(1): 485, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-29047408

RESUMO

BACKGROUND: Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. METHODS/DESIGN: This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. DISCUSSION: This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.


Assuntos
Anorexia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Kampo/métodos , Anorexia/induzido quimicamente , Anorexia/fisiopatologia , Anorexia/psicologia , Protocolos Clínicos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Japão , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
16.
Biol Pharm Bull ; 40(10): 1730-1738, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28781292

RESUMO

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.


Assuntos
Resfriado Comum/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Emoções/efeitos dos fármacos , Medicina Kampo/métodos , Medicamentos Compostos contra Resfriado, Influenza e Alergia/uso terapêutico , Resfriado Comum/fisiopatologia , Tosse/tratamento farmacológico , Feminino , Humanos , Masculino , Medicamentos sem Prescrição/administração & dosagem , Fatores Sexuais , Espirro/efeitos dos fármacos , Inquéritos e Questionários , Resultado do Tratamento
17.
J Nat Med ; 71(4): 757-764, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28695397

RESUMO

Oxaliplatin (L-OHP) is a platinum-based anticancer agent used to treat various types of cancer. It frequently causes acute and chronic peripheral neuropathies, such as cold allodynia and mechanical hyperalgesia. Ninjin'yoeito (NYT) is a formula used in traditional Japanese Kampo medicine to improve recovery from diseases and other medical disorders. We previously reported that treatment with a boiling-water extract of NYT prevented L-OHP-induced damage to neurite-like outgrowths from differentiated PC12 cells. The objectives of the present study were to evaluate the in vivo effects of NYT on L-OHP-induced neuropathic pain in mice and identify the active ingredients in NYT. Treatment with NYT extract significantly ameliorated both cold allodynia and mechanical hyperalgesia induced by L-OHP. While L-OHP treatment suppressed neurite outgrowths from primary dorsal root ganglion cells in vitro, NYT extract blocked this suppression in a concentration-dependent manner. Among the herbal components of NYT, the extract of ginseng (Panax ginseng roots) showed a protective effect against neurite damage induced by L-OHP, and one of its active ingredients was identified as ginsenoside Rg3. Ginseng extract partially relieved L-OHP-induced neuropathic pain in mice. Our results suggest that NYT could be an attractive agent for treating L-OHP-induced neuropathic pain, and that the active ingredient of NYT may be ginseng.


Assuntos
Medicina Kampo/métodos , Neuralgia/induzido quimicamente , Compostos Organoplatínicos/efeitos adversos , Panax/química , Animais , Masculino , Camundongos , Neuralgia/tratamento farmacológico , Oxaliplatina
18.
J Nat Med ; 71(4): 711-722, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28608269

RESUMO

Glycyrrhizae Radix is the most frequently used crude drug in Japan and is prescribed in Kampo medicine for the treatment of a wide range of diseases. The major active ingredient of Glycyrrhizae Radix, glycyrrhizin (GL), has been shown to possess various pharmacological actions, but is also known to cause adverse effects such as pseudoaldosteronism. To avoid the adverse effects of GL, precautions have been indicated on the package inserts of Glycyrrhizae Radix-containing formulas depending on the amount of Glycyrrhizae Radix they contain. However, it remains unknown whether the extraction efficiency of GL from Glycyrrhizae Radix is constant throughout the different combinations of crude drugs in Glycyrrhizae Radix-containing formulas. To confirm the basis of the safety regulation, in this study we comprehensively determined the GL content of 25 major kinds of Kampo extracts compounding Glycyrrhizae Radix. We found that the GL content per daily dosage in all Kampo extracts are generally proportional to the compounding amount of Glycyrrhizae Radix, except in the case of shoseiryuto (Sho-seiryu-To). We also found that Schisandrae Fructus in Sho-seiryu-To decoction caused a lowered pH condition and drastically decreased the extraction efficacy of GL from Glycyrrhizae Radix. Moreover, we were able to confirm that the extraction efficiency of GL from Glycyrrhizae Radix is dependent on the pH value of the extraction solvent. The extraction efficiency of GL in the 25 kinds of Kampo extracts was not constant but it correlates significantly with the pH value of the decoction. Furthermore, the GL contents are well correlated with pseudoaldosteronism incidence data obtained from the Japanese Adverse Drug Event Report (JADER) database on the 25 kinds of Kampo extracts. This suggests that the GL content is a better index to consider to avoid the adverse effects of Glycyrrhizae Radix-containing Kampo formulas.


Assuntos
Ácido Glicirrízico/uso terapêutico , Medicina Kampo/métodos , Extratos Vegetais/uso terapêutico , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/farmacologia , Japão , Extratos Vegetais/farmacologia
19.
Biomed Res Int ; 2017: 4575709, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28567419

RESUMO

Streptococcus pneumoniae (S. pneumoniae) is the important pathogen that causes otolaryngeal diseases such as sinusitis. S. pneumoniae frequently forms the biofilm to prevent severe circumstances such as antimicrobial agents. Shin'iseihaito (xinyiqingfeitang) is a formula of Japanese traditional Kampo medicine that has 9 crude drugs and provides the medicinal usage for sinusitis. The objective of the present study is to reveal the mechanism of antibiofilm activity by Shin'iseihaito extract (SSHT). SSHT significantly inhibited the formation of biofilm from S. pneumoniae ATCC 49619 in dose- and time-dependent manners. SSHT also significantly suppressed the biofilm formation by other five different cps types of S. pneumoniae clinical isolates. We found that the extracts of 8 out of 9 components in Shin'iseihaito had the inhibitory effects of biofilm formation, and the extract of the root of Scutellaria baicalensis had the strongest effect among the ingredients of Shin'iseihaito. We found that the capsule of SSHT-treated S. pneumoniae was significantly thinner than that of the untreated group and that SSHT reduced the hydrophobicity of bacterial cell surface. Our results suggest that Shin'iseihaito may be a useful agent for the treatment of S. pneumoniae-induced sinusitis because of the inhibition of biofilm formation of S. pneumoniae.


Assuntos
Biofilmes/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Kampo/métodos , Streptococcus pneumoniae/fisiologia , Humanos
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