Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 48
Filter
1.
Chem Pharm Bull (Tokyo) ; 70(12): 863-867, 2022.
Article in English | MEDLINE | ID: mdl-36450584

ABSTRACT

Apricot and Peach Kernels are commercial crude drugs used in many formulas of traditional Japanese medicine, Kampo. Although their applications are quite different, it is difficult to distinguish them using conventional methods such as HPLC. The study aimed at near-infrared (NIR) metabolic profiling to discriminate Apricot and Peach Kernels (Armeniacae Semen and Persicae Semen) collected from Japanese markets. A fast, simple, non-destructive, and robust NIR measurement of kernel surface with no sample pre-treatment was achieved in situ. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) models showed discrimination between the two crude drugs with good fitting and prediction values. These results indicate that NIR metabolic profiling is useful for discriminating Apricot and Peach Kernels based on their chemical constituents using a simple and non-destructive procedure.


Subject(s)
Prunus armeniaca , Prunus persica , Metabolomics , Principal Component Analysis , Chromatography, High Pressure Liquid
2.
Chem Pharm Bull (Tokyo) ; 68(2): 140-149, 2020.
Article in English | MEDLINE | ID: mdl-32009081

ABSTRACT

Previously, we reported that the c-Met inhibitory effect of Ephedra Herb extract (EHE) is derived from ingredients besides ephedrine alkaloids. Moreover, analgesic and anti-influenza activities of EHE and ephedrine alkaloids-free Ephedra Herb extract (EFE) have been reported recently. In this study, we examined the fractions containing c-Met kinase inhibitory activity from EHE and the fractions with analgesic and anti-influenza activities from EFE, and elucidated the structural characteristics of the active fractions. Significant c-Met kinase activity was observed in 30, 40, and 50% methanol (MeOH) eluate fractions obtained from water extract of EHE using Diaion HP-20 column chromatography. Similarly, 20 and 40% MeOH, and MeOH eluate fractions obtained from water extract of EFE were found to display analgesic and anti-influenza activities. Reversed phase-HPLC analysis of the active fractions commonly showed broad peaks characteristic of high-molecular mass condensed tannin. The active fractions were analyzed using 13C-NMR and decomposition reactions; the deduced structures of active components were high-molecular mass condensed tannins, which were mainly procyanidin B-type and partly procyanidin A-type, including pyrogallol- and catechol-type flavan 3-ols as extension and terminal units. HPLC and gel permeation chromatography (GPC) analyses estimated that the ratio of pyrogallol- and catechol-type was approximately 9 : 2, and the weight-average molecular weight based on the polystyrene standard was >45000. Furthermore, GPC-based analysis was proposed as the quality evaluation method for high-molecular mass condensed tannin in EHE and EFE.


Subject(s)
Ephedra/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Alkaloids/chemistry , Alkaloids/pharmacology , Analgesics/chemistry , Analgesics/pharmacology , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biflavonoids/chemistry , Biflavonoids/pharmacology , Catechin/chemistry , Catechin/pharmacology , Cell Line, Tumor , Dogs , Ephedrine/chemistry , Ephedrine/pharmacology , Humans , Madin Darby Canine Kidney Cells , Male , Mice , Proanthocyanidins/chemistry , Proanthocyanidins/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-met/antagonists & inhibitors
3.
Biol Pharm Bull ; 42(9): 1538-1544, 2019.
Article in English | MEDLINE | ID: mdl-31474713

ABSTRACT

The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids-free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0-5 min; second phase, 10-45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, "authentic" EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse-and at 4 to 6 h after administration of EHE-Ts-only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4-6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.


Subject(s)
Analgesics/therapeutic use , Ephedra/chemistry , Ephedrine/therapeutic use , Pain/drug therapy , Plant Extracts/therapeutic use , Pseudoephedrine/therapeutic use , Administration, Oral , Analgesics/isolation & purification , Animals , Disease Models, Animal , Male , Mice, Inbred Strains , Pain Measurement , Plant Extracts/isolation & purification , Rotarod Performance Test , Time Factors
4.
J Pharmacol Sci ; 137(4): 379-386, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30145033

ABSTRACT

Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (α7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI.


Subject(s)
Anti-Inflammatory Agents , Ileus/immunology , Neutrophil Infiltration/drug effects , Plant Extracts/pharmacology , Postoperative Complications/immunology , Receptors, Muscarinic/metabolism , Zingiberaceae/chemistry , Acetylcholine/metabolism , Administration, Oral , Animals , Disease Models, Animal , Enterochromaffin Cells/metabolism , Male , Mice, Inbred C57BL , Myenteric Plexus/metabolism , Panax , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Receptors, Serotonin, 5-HT4/metabolism , Serotonin/metabolism , TRPA1 Cation Channel/metabolism , Zanthoxylum
5.
Biol Pharm Bull ; 41(2): 247-253, 2018.
Article in English | MEDLINE | ID: mdl-29386484

ABSTRACT

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline ß1 receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.


Subject(s)
Anxiety/prevention & control , Arrhythmias, Cardiac/prevention & control , Dietary Supplements/adverse effects , Ephedra/chemistry , Ephedrine/adverse effects , Plant Extracts/adverse effects , Sleep Initiation and Maintenance Disorders/prevention & control , Alkaloids/analysis , Alkaloids/toxicity , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/chemistry , Animals , Animals, Outbred Strains , Anxiety/blood , Anxiety/chemically induced , Anxiety/etiology , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/etiology , Behavior, Animal , Caffeine/poisoning , Central Nervous System Stimulants/poisoning , Dietary Supplements/analysis , Ephedrine/administration & dosage , Ephedrine/chemistry , Food Contamination , Hypnotics and Sedatives/pharmacology , Japan , Male , Mice , Pentobarbital/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Stems/chemistry , Potassium/blood , Sleep Initiation and Maintenance Disorders/blood , Sleep Initiation and Maintenance Disorders/chemically induced , Sleep Initiation and Maintenance Disorders/etiology
6.
J Neuroinflammation ; 14(1): 98, 2017 05 03.
Article in English | MEDLINE | ID: mdl-28468634

ABSTRACT

BACKGROUND: Kososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS. METHODS: In the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1-10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1-12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13-15. RESULTS: Oral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment. CONCLUSIONS: Our findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.


Subject(s)
Avoidance Learning/drug effects , Drugs, Chinese Herbal/pharmacology , Inflammation Mediators/antagonists & inhibitors , Medicine, Kampo , Plant Extracts/pharmacology , Social Behavior , Animals , Avoidance Learning/physiology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/therapeutic use , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred C57BL , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Stress, Psychological/pathology
7.
J Pharmacol Sci ; 124(3): 374-85, 2014.
Article in English | MEDLINE | ID: mdl-24572814

ABSTRACT

Rikkunshito (RKT), a Kampo (Japanese herbal) medicine, is used as a prokinetic for patients with various diseases including functional dyspepsia. RKT promotes delayed gastric emptying via 5-HT3 receptor blockade. Otherwise, RKT increases ghrelin release via 5-HT2B and 5-HT2C receptor activation. Recent studies revealed that ghrelin and 5-HT3 receptor antagonists have an anti-inflammatory effect. So we hypothesize that RKT may have an anti-inflammatory action in the post-operative ileus. Intestinal manipulation (IM) was applied to the distal ileum of mice. RKT was administered orally 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, and gastric emptying were analyzed. We also investigated the effects of the 5-HT3 receptor agonist m-chlorophenylbiguamide (mCPBG) and ghrelin-receptor antagonist [D-Lys3]-GHRP-6 on the ameliorative action of RKT. RKT treatment led to recovery of the delayed intestinal transit and gastric emptying rate induced by IM. RKT significantly inhibited the infiltration of neutrophils and macrophages. [D-Lys3]-GHRP-6 reduced and mCPBG partially reduced the RKT-mediated anti-inflammatory activity, as monitored by infiltrating macrophages and neutrophils. RKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency, in addition to prokinetic action. The RKT-induced anti-inflammatory activity may be partly mediated by inhibition of the 5-HT3 receptor and ghrelin release.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Ileus/drug therapy , Medicine, Kampo , Phytotherapy , Postoperative Complications/drug therapy , Administration, Ophthalmic , Animals , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Gastric Emptying/drug effects , Gastric Emptying/genetics , Ghrelin/metabolism , Male , Mice , Mice, Inbred BALB C , Neutrophil Infiltration/drug effects , Serotonin 5-HT3 Receptor Antagonists
8.
J Pharmacol Sci ; 123(2): 176-84, 2013.
Article in English | MEDLINE | ID: mdl-24096835

ABSTRACT

The conventional method for the real-time assessment of murine colitis requires a large number of animals. The (13)C-butyrate breath test could be useful for evaluating disease activity and the amelioration of human ulcerative colitis non-invasively. The purpose of this study was to investigate whether this test can be used to assess the phase of inflammation in murine colitis. We investigated the excretion of (13)CO2 measured by the (13)C-butyrate breath test after rectal instillation of butyrate in the DSS colitis model. The colon length, MPO activity, and histological damage were analyzed as parameters. The efficacy of salicylazosulfa-pyridine (SASP) on (13)CO2 excretion was also studied. The (13)CO2 excretion curves in the 0.5% DSS- and 0.75% DSS-treated groups were significantly lower than those in the normal group (P < 0.01, P < 0.01). Good correlation between the results of the breath test and the inflammation parameters was observed. The (13)CO2 excretion curve in DSS murine colitis after the administration of SASP was significantly higher than in the normal group (P < 0.01). The (13)C-butyrate breath test can be used to evaluate the inflammatory phase of DSS murine colitis, and it may be a new non-invasive method for assessing murine colitis.


Subject(s)
Breath Tests/methods , Butyrates , Colitis, Ulcerative/diagnosis , Disease Models, Animal , Administration, Rectal , Animals , Biomarkers/analysis , Butyrates/administration & dosage , Carbon Dioxide/analysis , Carbon Isotopes/analysis , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Colon/enzymology , Colon/pathology , Dextran Sulfate , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mustard Plant , Peroxidase/metabolism , Plant Oils , Sulfasalazine/analogs & derivatives , Sulfasalazine/therapeutic use
9.
Planta Med ; 79(16): 1525-30, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24081687

ABSTRACT

Ephedrae herba suppresses hepatocyte growth factor-induced cancer cell motility by inhibiting tyrosine phosphorylation of the hepatocyte growth factor receptor, c-Met, and the PI3K/Akt pathway. Moreover, Ephedrae herba directly inhibits the tyrosine-kinase activity of c-Met. Ephedrine-type alkaloids, which are the active component of Ephedrae herba, do not affect hepatocyte growth factor-c-Met-Akt signalling, prompting us to study other active molecules in the herb. We recently discovered herbacetin glycosides and found that their aglycon, herbacetin, inhibits hepatocyte growth factor-c-Met-Akt signalling. This study revealed a novel biological activity of herbacetin. Herbacetin suppressed hepatocyte growth factor-induced motility in human breast cancer MDA-MB-231 cells by inhibiting c-Met and Akt phosphorylation and directly inhibiting c-Met tyrosine kinase activity. The effects of herbacetin were compared to those of kaempferol, apigenin, and isoscutellarein, all of which have similar structures. Herbacetin inhibition of hepatocyte growth factor-induced motility was the strongest of those for the tested flavonols, and only herbacetin inhibited the hepatocyte growth factor-induced phosphorylation of c-Met. These data suggest that herbacetin is a novel Met inhibitor with a potential utility in cancer therapeutics.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/pathology , Cell Movement/drug effects , Flavonoids/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-met/metabolism , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Flavonoids/chemistry , Hepatocyte Growth Factor/physiology , Humans , Phosphorylation/drug effects , Plants, Medicinal
10.
Molecules ; 18(5): 5326-34, 2013 May 10.
Article in English | MEDLINE | ID: mdl-23666001

ABSTRACT

Nine known compounds: trans-cinnamic acid, catechin, syringin, epicatechin, symplocoside, kaempferol 3-O-rhamnoside 7-O-glucoside, isovitexin 2-O-rhamnoside, herbacetin 7-O-glucoside, and pollenitin B and a new flavonoid glycoside, characterized as herbacetin 7-O-neohesperidoside (1) on the basis of spectroscopic analysis and chemical evidence, were isolated from a traditional crude drug, "Ephedra herb extract". Compound 1 had no effects on HGF-induced motility, whereas herbacetin, which is an aglycone of 1, significantly inhibited it.


Subject(s)
Benzoates , Cell Movement/drug effects , Ephedra/chemistry , Plant Extracts/chemistry , Benzoates/chemistry , Benzoates/isolation & purification , Benzoates/pharmacology , Hepatocyte Growth Factor/pharmacology , Humans , Medicine, Kampo
11.
J Nat Med ; 77(3): 523-534, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37043119

ABSTRACT

We previously reported that the combined application of Ephedra Herb extract (EHE) and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), erlotinib, is effective in suppressing the growth of erlotinib-resistant non-small-cell lung cancer (NSCLC) cell line, H1993, xenograft tumor, and cell proliferation, and that EHE downregulates c-Met and wild-type EGFR in H1993 cells. However, it was unclear whether EHE could affect EGFR with active mutations. Clinically, advanced NSCLC patients who are eligible for EGFR-TKI treatment are those with detected EGFR with activating mutations. Therefore, it is important to clarify the effect of EHE on EGFR with activating mutations. H1975 cells express EGFR with activating mutations, L858R and T790M, and c-Met; this NSCLC cell line was used in the present study. EHE downregulated the expression of EGFR with activating mutations and c-Met, and inhibited autophosphorylation of c-Met. Proliferation of H1975 cells was suppressed by EHE in a concentration-dependent manner. These results suggest that EHE may be effective against NSCLC harboring EGFR with activating mutations. Considering the fact that advanced NSCLC patients, with an EGFR T790M mutation, are currently widely treated with the third-generation EGFR-TKI, osimertinib, we examined the combined effects of osimertinib and EHE on H1975 cells. The osimertinib and EHE combination downregulated the expression of these receptors and suppressed the proliferation of H1975 cells more effectively than did osimertinib alone, suggesting that this combination may be effective in treating patients with advanced NSCLC with the L858R + T790M EGFR mutation and c-Met. Graphical Abstract was created with BioRender.com.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Erlotinib Hydrochloride , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Protein Kinase Inhibitors/pharmacology , Mutation , Cell Line , Cell Line, Tumor
12.
J Ethnopharmacol ; 301: 115827, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36240977

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In our previous study, we reported that Ephedra Herb extract (EHE) increased the locomotor activity of mice in the open-field test and reduced the immobility time in the forced swim test. Ephedrine alkaloids (EAs) are thought to be responsible for the adverse effects of Ephedra Herb. However, there are no reports to verify that the adverse effects of Ephedra Herb are caused by the amount of EAs in the herb. Therefore, we investigated whether these adverse effects of EHE are caused by the amounts of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract. In a preliminary study of the time course analysis of the open field test, we newly observed that EHE evoked switching from transient sedation to sustained excitement. AIM OF THE STUDY: We aimed to confirm whether EHE evokes switching from transient sedation to sustained excitement, investigate whether these actions of EHE are caused by the amount of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract, and clarify the molecular mechanism of the transient sedative effect. MATERIALS AND METHODS: The locomotor activity of mice was tested using the open-field test. The immobility times were measured using a forced swim test, and the motor dysfunction in mice was tested using the rotarod test. RESULTS: EHE, Eph, and Pse induced transient motionlessness between 0 and 15 min after oral administration, however, they did not induce depression-like behavior and motor dysfunction in mice, suggesting that the motionlessness induced by EHE, Eph, or Pse resulted from sedation. The α2a adrenoceptor inhibitor, atipamezole, decreased their sedative effects. Thus, immediately after EHE administration, the transient sedative effect is mediated through the activation of the α2a adrenoreceptor by Eph and Pse. EHE and Eph increased total locomotor activity for 15-120 min after oral administration; however, Pse had no effect. Therefore, the slow-onset and sustained excitatory effects of EHE are mediated by Eph. CONCLUSIONS: We discovered for the first time that EHE evokes diphasic action by switching from transient sedation to sustained excitement. The transient sedation was evoked by the Eph and Pse in the herbal extract via activation of the α2a adrenoceptor and the sustained excitement was caused by the Eph in the herbal extract.


Subject(s)
Alkaloids , Ephedra , Mice , Animals , Ephedra/chemistry , Ephedrine/pharmacology , Pseudoephedrine , Alkaloids/chemistry , Plant Extracts/chemistry , Hypnotics and Sedatives/pharmacology , Receptors, Adrenergic
13.
Biol Pharm Bull ; 35(10): 1729-39, 2012.
Article in English | MEDLINE | ID: mdl-23037162

ABSTRACT

Paclitaxel-resistant HuH-7 (HuH-7/PTX) cells were established by one-week exposure of HuH-7 cells to paclitaxel to analyze the effects of Kampo medicines on MDR-1-mediated multidrug resistance. HuH-7/PTX cells expressed high levels of MDR-1 and efficiently exported calcein-acetoxymethylester (calcein-AM), which is a substrate of MDR-1, suggesting that HuH-7/PTX cells resist paclitaxel by overexpressing MDR-1. We assessed the effects of 26 kinds of Kampo medicine on MDR-1 by calcein-AM efflux assay using HuH-7/PTX cells, and the results revealed that takushato and goreisan are potential inhibitors of drug efflux by MDR-1. Additionally, the sensitivity of HuH-7/PTX cells to paclitaxel was increased in combination with these Kampo medicines, indicating that takushato and goreisan overcame paclitaxel resistance in the cells by suppressing drug export by MDR-1. We further clarified that Alismatis Rhizoma contained in both takushato and goreisan reversed paclitaxel resistance by preventing drug efflux by MDR-1 without affecting the expression levels of MDR-1. Moreover, the principal components of Alismatis Rhizoma, Alisol A, Alisol B, and Alisol B acetate, were found to increase the sensitivity to paclitaxel in HuH-7/PTX by inhibiting drug export by MDR-1 without affecting the expression levels of MDR-1. These results suggested that the reversal effects of takushato and goreisan on paclitaxel resistance are derived from these principal components in Alismatis Rhizoma. Accordingly, Kampo medicines containing Alismatis Rhizoma such as takushato and goreisan may be useful as MDR-1 inhibitors.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Drugs, Chinese Herbal/pharmacology , Medicine, Kampo , Paclitaxel/pharmacology , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Carcinoma, Hepatocellular , Cell Line, Tumor , Humans
14.
Biol Pharm Bull ; 35(10): 1775-83, 2012.
Article in English | MEDLINE | ID: mdl-23037167

ABSTRACT

Neuropeptide Y (NPY) and Orexin-A (OX-A), well-known neuropeptides associated with feeding and arousal, show antidepressant-like properties via hippocampal cell proliferation. Previous studies have revealed that kososan, a Kampo (Japanese herbal) medicine, has an antidepressant-like effect in behavioral animal models of depression; the mechanisms underlying this effect may involve the orexinergic system and subsequent upregulation of hippocampal cell proliferation. However, the roles of NPY in kososan's antidepressant-like effect remain unclear. Here we investigated whether the regulation of the NPY system could play crucial roles in this effect in the stress-induced depression-like model mice. The antidepressant-like effect of kososan administered orally (1.0 g/kg) for 28 d was abolished by a continuous intracerebroventricular injection of BIBO3304, a neuropeptide Y1 receptor antagonist, for 7 d. Likewise, BIBO3304 injection blocked the kososan-induced increases in hippocampal cell proliferation and cluster formation of neural progenitor cells. On the other hand, BIBO3304 injection did not affect kososan-induced increases in hypothalamic OX-A-producing cells or in serum OX-A levels. These results suggest that the control of the NPY system in the brain plays an essential role in kososan's antidepressant-like effect and facilitates hippocampal cell proliferation, both of which could be attributed, at least in part, to the control of the NPY system subsequent to the control of the OX-A system.


Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Drugs, Chinese Herbal/therapeutic use , Neuropeptide Y/metabolism , Stress, Psychological/drug therapy , Animals , Antidepressive Agents/pharmacology , Arginine/analogs & derivatives , Arginine/pharmacology , Cell Proliferation/drug effects , Depression/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Hippocampus/cytology , Hippocampus/drug effects , Hippocampus/metabolism , Intracellular Signaling Peptides and Proteins/blood , Male , Medicine, Kampo , Mice , Neuropeptide Y/antagonists & inhibitors , Neuropeptides/blood , Orexins , Signal Transduction/drug effects , Stress, Psychological/metabolism
15.
BMC Complement Altern Med ; 12: 207, 2012 Nov 02.
Article in English | MEDLINE | ID: mdl-23122050

ABSTRACT

BACKGROUND: There have been a few but not precise surveys of the current status of traditional Japanese Kampo education at medical schools in Japan. Our aim was to identify problems and suggest solutions for a standardized Kampo educational model for all medical schools throughout Japan. METHODS: We surveyed all 80 medical schools in Japan regarding eight items related to teaching or studying Kampo medicine: (1) the number of class meetings, target school year(s), and type of classes; (2) presence or absence of full-time instructors; (3) curricula contents; (4) textbooks in use; (5) desire for standardized textbooks; (6) faculty development programmes; (7) course contents; and (8) problems to be solved to promote Kampo education. We conducted descriptive analyses without statistics. RESULTS: Eighty questionnaires were collected (100%). (1) There were 0 to 25 Kampo class meetings during the 6 years of medical school. At least one Kampo class was conducted at 98% of the schools, ≥4 at 84%, ≥8 at 44%, and ≥16 at 5%. Distribution of classes was 19% and 57% for third- and fourth-year students, respectively. (2) Only 29% of schools employed full-time Kampo medicine instructors. (3) Medicine was taught on the basis of traditional Japanese Kampo medicine by 81% of the schools, Chinese medicine by 19%, and Western medicine by 20%. (4) Textbooks were used by 24%. (5) Seventy-four percent considered using standardized textbooks. (6) Thirty-three percent provided faculty development programmes. (7) Regarding course contents, "characteristics" was selected by 94%, "basic concepts" by 84%, and evidence-based medicine by 64%. (8) Among the problems to be solved promptly, curriculum standardization was selected by 63%, preparation of simple textbooks by 51%, and fostering instructors responsible for Kampo education by 65%. CONCLUSIONS: Japanese medical schools only offer students a short time to study Kampo medicine, and the impetus to include Kampo medicine in their curricula varies among schools. Future Kampo education at medical schools requires solving several problems, including curriculum standardization.


Subject(s)
Curriculum , Medicine, Kampo , Schools, Medical , Evidence-Based Medicine , Faculty , Humans , Japan , Surveys and Questionnaires , Textbooks as Topic
16.
J Smooth Muscle Res ; 58: 78-88, 2022.
Article in English | MEDLINE | ID: mdl-36216552

ABSTRACT

BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT. METHODS: HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed. RESULTS: HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.


Subject(s)
Anti-Inflammatory Agents , Ileus , Plant Preparations , Plants, Medicinal , Allyl Compounds , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Biphenyl Compounds , Ileus/drug therapy , Inflammation Mediators , Interleukin-6/therapeutic use , Japan , Mice , NF-kappa B/therapeutic use , Nerve Growth Factor/therapeutic use , Nitric Oxide Synthase Type II/therapeutic use , Phenols , Plant Preparations/pharmacology , Plant Preparations/therapeutic use , Postoperative Complications/drug therapy
17.
Front Pharmacol ; 13: 688074, 2022.
Article in English | MEDLINE | ID: mdl-35571074

ABSTRACT

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.

18.
Article in English | MEDLINE | ID: mdl-33868438

ABSTRACT

Shofuku-fujin is an abnormal physical finding in Kampo medical practice. It is assumed to be often found in the elderly and contributes to the selection of Kampo formulas used mainly in elderly patients. However, few objective reports about Shofuku-fujin have been published to date. The aim of this study was to clarify the clinical features of patients showing Shofuku-fujin by using bioelectrical impedance analysis (BIA) and to objectively assess the potential clinical implications of these findings. We conducted a cross-sectional study of 1330 patients who visited our institute to undergo a medical examination by using data collected from September 2010 to March 2016. We extracted data on patient sex and age, anthropometric data, and body composition data that could potentially affect the appearance of Shofuku-fujin. Logistic regression analyses were performed by sex to analyze the various factors related to the appearance of Shofuku-fujin. Of the 1330 patients, the data of 386 men and 942 women were used for analysis. Multivariate logistic regression analysis showed that Shofuku-fujin was associated with older age (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.05-1.10; p < 0.001), lower skeletal muscle mass index (SMI) (OR, 0.60; 95% CI, 0.43-0.85; p = 0.004), and lower body fat percentage (OR, 0.89; 95% CI, 0.85-0.93; p < 0.001) in men and older age (OR, 1.06; 95% CI, 1.04-1.07, p < 0.001) and lower body fat percentage (OR, 0.94; 95% CI, 0.92-0.96; p < 0.001) in women. On the basis of these results, the factors causing the appearance of Shofuku-fujin were aging, decreased muscle mass, and decreased body fat in men and aging and decreased body fat in women. Our results demonstrated that it may be better to consider a loss of muscle mass when examining a male patient with Shofuku-fujin.

19.
Tokai J Exp Clin Med ; 46(2): 75-82, 2021 Jul 20.
Article in English | MEDLINE | ID: mdl-34216479

ABSTRACT

OBJECTIVE: To examine how Kampo education in Japanese medical schools changed between 2011 and 2019. METHODS: We administered nationwide postal questionnaire surveys about current characteristics of Kampo medicine education in all 82 Japanese medical schools, directed to the persons responsible for Kampo education at each university. One survey was conducted in 2011 and one in 2019. Analysis used Welch's t-test and a chi-squared test. RESULTS: The average class meeting time was shorter in 2019 than in 2011. The proportion of class meetings that were about Kampo saw a statistically significant increase in the third year and a significant decrease in the fourth and sixth years of medical school. Curriculum standardisation, preparation of simple textbooks, and fostering Kampo medicine instructors were the primary problems in both years. The proportion of mainstream medical education contents focusing on traditional Japanese Kampo medicine did not change over time, nor did the percentage of those considering using standardised textbooks. Other changes were statistically nonsignificant. CONCLUSION: In Japanese medical schools, the number of class meetings teaching Kampo medicine has increased; however, this number is not statistically significant. Persistent problems in Kampo education, including curriculum standardisation, need to be addressed.


Subject(s)
Education, Medical , Medicine, Kampo , Curriculum , Humans , Japan , Schools, Medical
20.
J Nat Med ; 75(3): 475-488, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33569695

ABSTRACT

Identifying different species of the genus Atractylodes which are commonly used in Chinese and Japanese traditional medicine, using chromatographic approaches can be difficult. 1H NMR metabolic profiling of DNA-authenticated, archived rhizomes of the genus Atractylodes was performed for genetic and chemical evaluation. The ITS region of the nuclear rDNA was sequenced for five species, A. japonica, A. macrocephala, A. lancea, A. chinensis, and A. koreana. Our samples had nucleotide sequences as previously reported, except that part of the A. lancea cultivated in Japan had a type 5, hybrid DNA sequence. Principal component analysis (PCA) using 1H NMR spectra of extracts with two solvent systems (CD3OD, CDCl3) was performed. When CDCl3 extracts were utilized, the chemometric analysis enabled the identification and classification of Atractylodes species according to their composition of major sesquiterpene compounds. The 1H NMR spectra using CD3OD contained confounding sugar peaks. PCA removal of these peaks gave the same result as that obtained using CDCl3 and allowed species distinction. Such chemometric methods with multivariate analysis of NMR spectra will be useful for the discrimination of plant species, without specifying the index components and quantitative analysis on multi-components.


Subject(s)
Atractylodes/chemistry , Atractylodes/classification , Metabolomics , Phytochemicals/analysis , Base Sequence , DNA, Plant/genetics , DNA, Ribosomal Spacer/genetics , Japan , Magnetic Resonance Spectroscopy , Phylogeny , Principal Component Analysis , Rhizome/chemistry , Rhizome/genetics , Sesquiterpenes/analysis
SELECTION OF CITATIONS
SEARCH DETAIL