Analysis of the Antioxidative Function of the Radioprotective Japanese Traditional (Kampo) Medicine, Hangeshashinto, in an Aqueous Phase

Oral mucositis (OM) is a common and painful complication of radiotherapy for head and neck cancer. Hangeshashinto (HST), a Japanese traditional medicine, is known to alleviate radiotherapy and/or chemotherapy-induced OM; however, the detailed mechanism has not yet been clarified. The aim of the present study is to clarify the details of the antioxidative functions of HST against reactive oxygen species (ROS) produced by radiation. The hydroxyl radical (•OH) scavenging ability and reduction ability was simultaneously measured using a modified electron paramagnetic resonance (EPR) spin trapping method. The superoxide (O2•−) scavenging ability was estimated by an EPR redox probing method. Water suspension of powdered HST and its seven constitutive crude drugs were tested. In addition, some of the main water soluble ingredients of the crude drugs were also tested. HST was found to scavenge both •OH and O2•−. Furthermore, HST was observed to reduce relatively stable nitroxyl radicals. Glycyrrhizae Radix (kanzo), Ginseng Radix (ninjin), Zizyphi Fructus (taiso), and glycyrrhizin (an ingredient of kanzo) were all found to be relatively good •OH scavengers. Scutellariae Radix (ogon) and Coptidis Rhizoma (oren) demonstrated reducing ability. In addition, acteoside and berberine chloride, which are water soluble ingredients of ogon and oren, respectively, also demonstrated reducing ability. Oren exhibited oxidative ability at higher concentrations, which may have a function to maintain catalytic redox action. The antioxidative function of HST probably worked in a balance of scavenging ROS, reducing stable free radicals and some minor oxidative effects

Unkeito promotes follicle development by restoring reduced follicle-stimulating hormone responsiveness in rats with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a common disorder resulting in irregular menstruation and infertility due to improper follicular development and ovulation. PCOS pathogenesis is mediated by downregulated follicle-stimulating hormone receptor (FSHR) expression in granulosa cells (GCs); however, the underlying mechanism remains elusive. Unkeito (UKT) is a traditional Japanese medicine used to treat irregular menstruation in patients with PCOS. In this study, we aimed to confirm the effectiveness of UKT in PCOS by focusing on follicle-stimulating hormone (FSH) responsiveness.MethodsA rat model of PCOS was generated by prenatal treatment with 5α-dihydrotestosterone. Female offspring (3-week-old) rats were fed a UKT mixed diet or a normal diet daily. To compare the PCOS phenotype in rats, the estrous cycle, hormone profiles, and ovarian morphology were evaluated. To further examine the role of FSH, molecular, genetic, and immunohistological analyses were performed using ovarian tissues and primary cultured GCs from normal and PCOS model rats.ResultsUKT increased the number of antral and preovulatory follicles and restored the irregular estrous cycle in PCOS rats. The gene expression levels of FSHR and bone morphogenetic protein (BMP)-2 and BMP-6 were significantly decreased in the ovarian GCs of PCOS rats compared to those in normal rats. UKT treatment increased FSHR staining in the small antral follicles and upregulated Fshr and Bmps expression in the ovary and GCs of PCOS rats. There was no change in serum gonadotropin levels. In primary cultured GCs stimulated by FSH, UKT enhanced estradiol production, accompanied by increased intracellular cyclic adenosine monophosphate levels, and upregulated the expression of genes encoding the enzymes involved in local estradiol synthesis, namely Cyp19a1 and Hsd17b. Furthermore, UKT elevated the expression of Star and Cyp11a1, involved in progesterone production in cultured GCs in the presence of FSH.ConclusionsUKT stimulates ovarian follicle development by potentiating FSH responsiveness by upregulating BMP-2 and BMP-6 expression, resulting in the recovery of estrous cycle abnormalities in PCOS rats. Restoring the FSHR dysfunction in the small antral follicles may alleviate the PCOS phenotype

A Proteomic Approach for the Diagnosis of ‘Oketsu’ (blood stasis), a Pathophysiologic Concept of Japanese Traditional (Kampo) Medicine

‘Oketsu’ is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for ‘Oketsu’. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving ‘Oketsu’. Plasma samples were diagnosed as either having an ‘Oketsu’ (n = 19) or ‘non-Oketsu’ (n = 29) state according to Terasawa's ‘Oketsu’ scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the ‘Oketsu’ scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the ‘Oketsu’ and ‘non-Oketsu’ states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of ‘Oketsu’ samples were clustered into one cluster as the principal component of cluster I. The remaining ‘Oketsu’ profiles constituted a minor component of cluster II and were all derived from patients cured of the ‘Oketsu’ state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for ‘Oketsu’. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine ‘Oketsu’ has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing ‘Oketsu’ using a combination of proteomic and bioinformatics-based classification methods

Classroom management inservice for beginning teachers

The purpose of this study was to expand and clarify the understanding of how an inservice training program which incorporated research-based classroom management principles and practices combined with coaching techniques would enable new teachers to reduce class rates of off task behavior and feel more self-efficacious about their classroom management skills. Data on the occurrence of three categories of off task behavior for students in 6 classrooms in a single school district in central California were collected during pre-treatment and post-treatment conditions and during a maintenance condition for experimental group classes only. During the interval between the two conditions, the 3 experimental group teachers participated in an inservice training program developed by the investigator. The classrooms were paired, 1 experimental and 1 control, within schools for grade level and the teachers\u27 years of experience. Information from pre-questionnaires and post-questionnaires/interviews was used to assess the teachers\u27 feelings of self-efficacy related to classroom management and the effects of participation in the inservice training experiences on those feelings of self-efficacy. A descriptive analysis of the observation data did not indicate a positive effect from the inservice training experiences from either baseline to post-treatment or post-treatment to maintenance observations. However, information from the post-questionnaires/interviews indicated that the 3 experimental group teachers strongly felt that the inservice training experiences had positively affected their feelings of competence and control in the classroom. A possible reason for the conflicting findings may have been that the inservice experiences helped the teachers to reconceptualize their beliefs and expectations about classroom management. This study supports the hypothesis that inservice training which incorporates research-based practices of effective classroom management and coaching techniques embedded in a collegial approach result in the improvement of teachers\u27 feelings of self-efficacy. This study recommends that beginning teachers, especially in inner-city schools, desperately need psychological support as well as personalized inservice training in effective teaching and classroom management methodology during their early years in teaching

Classroom management inservice for beginning teachers

The purpose of this study was to expand and clarify the understanding of how an inservice training program which incorporated research-based classroom management principles and practices combined with coaching techniques would enable new teachers to reduce class rates of off task behavior and feel more self-efficacious about their classroom management skills. Data on the occurrence of three categories of off task behavior for students in 6 classrooms in a single school district in central California were collected during pre-treatment and post-treatment conditions and during a maintenance condition for experimental group classes only. During the interval between the two conditions, the 3 experimental group teachers participated in an inservice training program developed by the investigator. The classrooms were paired, 1 experimental and 1 control, within schools for grade level and the teachers\u27 years of experience. Information from pre-questionnaires and post-questionnaires/interviews was used to assess the teachers\u27 feelings of self-efficacy related to classroom management and the effects of participation in the inservice training experiences on those feelings of self-efficacy. A descriptive analysis of the observation data did not indicate a positive effect from the inservice training experiences from either baseline to post-treatment or post-treatment to maintenance observations. However, information from the post-questionnaires/interviews indicated that the 3 experimental group teachers strongly felt that the inservice training experiences had positively affected their feelings of competence and control in the classroom. A possible reason for the conflicting findings may have been that the inservice experiences helped the teachers to reconceptualize their beliefs and expectations about classroom management. This study supports the hypothesis that inservice training which incorporates research-based practices of effective classroom management and coaching techniques embedded in a collegial approach result in the improvement of teachers\u27 feelings of self-efficacy. This study recommends that beginning teachers, especially in inner-city schools, desperately need psychological support as well as personalized inservice training in effective teaching and classroom management methodology during their early years in teaching

Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation

Sex differences exist in the activation of the hypothalamic-pituitary-adrenal axis following exposure to stress, and the stress response is further affected by aging. This study was conducted to elucidate the mechanism of hypophagia in aged female mice exposed to stress. Immediately after a stress load, aged female mice exhibited acute hypophagia and a rise in plasma corticosterone levels. The administration of a serotonin 2C receptor (5-T2CR) antagonist suppressed plasma corticosterone but did not affect the reduction in food intake. In contrast, an endogenous ghrelin enhancer, rikkunshito (RKT), significantly inhibited the reduction in food intake. An increase in peripheral acylated ghrelin levels during fasting, which occurs in young mice, was not observed in aged female mice. Moreover, in these mice, significantly increased levels of ghrelin and gastric preproghrelin mRNA expression were observed in the fed status. Moreover, plasma ghrelin levels were elevated by RKT and not by the 5-HT2CR antagonist. In female mice, the hypothalamic non-edited (INI) and partially edited mRNA 5-HT2CR isoforms (VNV, VNI, VSV or VSI) decreased with age, while in male mice, the editing isoform was unchanged by aging or stress. Estrogen receptor alpha (ER alpha)-positive cell counts in the arcuate nucleus of young male mice exposed to stress and control aged male mice were increased compared with those in young control mice. In aged male mice exposed to stress, the number of ER alpha-expressing cells in the paraventricular nucleus were significantly increased compared with those in aged control mice; in female mice, there was no increase in the number of ER alpha-positive cells. Hypophagia in aged female mice exposed to stress may be independent of 5-HT2CR activation. It seems likely that the mechanisms may be caused by sex dependent, differential regulation in 5-HT2CR mRNA expression, peripheral acylated ghrelin secretion and/or hypothalamic ER alpha expression

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect

Abstract Background TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. Methods Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. Results After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. Conclusion This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.</p