Helianthus tuberosus (Jerusalem artichoke) tubers improve glucose tolerance and hepatic lipid profile in rats fed a high-fat diet

Objectives: To analyze the effects of feeding Helianthus tuberosus (HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet (HFD). Methods: A normal HFD or HFD including 10 w/w% HT tubers (HFD + HT) was fed to F334/Jcl rats. After 10 weeks, organ weights, glucose tolerance, and lipid profile were analyzed. Results: The body weight, liver weight, and epidermal fat content in the HFD group were higher than those of the normal group, and similar to those of the HFD + HT group. The oral glucose tolerance test at 10 weeks revealed that the blood glucose level 30 min after beginning the test in the HFD + HT group was significantly lower than that in the HFD group. Liver triglyceride and total cholesterol levels in the HFD + HT group were significantly lower than those in the HFD group. Fecal triglyceride and total cholesterol levels in the HFD + HT group were higher than those in the HFD group. Histological analyses revealed that fat and glycogen accumulation increased in the HFD group, but decreased in the HFD + HT group. Conclusions: These results indicate that HT tubers have anti-fatty liver effects based on improvements in glucose tolerance and the hepatic lipid profile

CD56抗原を指標としたNK様培養細胞の活性評価

NK cells play an important role in the elimination of viral infection and tumors. In recent years, immune cell therapy using activated NK cells has attracted attention, and the search for activators and evaluation of NK cell activity have become important. We previously reported a positive correlation between CD５６antigen expression, which is the major cell membrane antigen of human NK cells, and NK cell activity or cytotoxicity, and demonstrated that it is possible to evaluate NK cell function using the CD５６ antigen as an index. This simple evaluation method is useful for functional evaluation of NK cells and the search for activators. However, it requires blood sampling and preparation of NK cells because it uses human NK cells. Therefore, in this study, we examined whether the CD５６ antigen functions as an activation index using KHYG‐１ human NK-like cultured cells as a substitute for NK cells. As a result, the CD５６antigen on the KHYG‐１cell membrane was increased in a concentration-dependent manner by IL‐２ stimulation, as was the cytotoxicity. This suggests that the CD５６ antigen on the KHYG‐１ cell membrane can be used as an evaluation index of NK activity as in human NK cells

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Background: In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy. Methods: Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay. Results: Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn’t influence cytotoxicity of paclitaxel in A549 cells. Conclusions: Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel

Effects of various drugs on platelet functions

Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Materials and methods: Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM) and cilostazol (5–10 µM) significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM) and sodium valproate (50–1,000 µg/mL) also significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca2+]i. Conclusion: It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca2+]i is applicable to the evaluation of the effects of various drugs on platelets

Rasio Senyawa Enansiomer sesamin di dalam kulit batang Pentaspadon motleyi (Anacardiaceae)

The barks of Pentaspadon motleyi Hook. f. (Anacardiaceae) were collected from the Poso district in Central Sulawesi, Indonesia, in 1992 which it has been used traditionally as a remedy for malaria and tuberculosis in the local area. It was found that a mixture of (+)-sesamin (1) and (-)-sesamin (2) in a ratio of 100:86 were present together with lupeol in the bark of Pentaspadon motleyi. This was the first evidence of sesamin being isolated in almost equivalent amounts of (+)- and (-)-forms from a single plant species, and indicates that the biosynthetic pathway of sesamin in the plant is not enantioselective or fuzzy.Kulit batang Pentaspadon motleyi Hook. F (Anacardiaceae ) yang dikoleksi dari daerah Poso (Sulawesi Tengah), Indonesia tahun 1992 dan secara tradisional digunakan untuk pengobatan malaria dan tuberkolosis. Senyawa kimia dalam bentuk campuran (+)-sesamin (1) dan (-)-sesamin (2) dengan perbandingan 100:86 bersama dengan senyawa lupeol telah ditemukan dari kulit batang Pentaspadon motleyi. Ini adalah laporan yang pertama kali bahwa sesamin yang diisolasi yang mempunyai jumlah hampir sama antara (+)-sesamin dan (-)-sesamin dari satu spesies tanaman ini, dan ini menunjukkan bahwa jalan biosíntesis sesamin dalam tanaman tersebut tidak enansioselektif atau tidak begitu jelas

KHYG‐１における細胞傷害性と細胞傷害性顆粒の変化

Three major therapies, “surgery”, “chemotherapy”, and “radiotherapy”, have been used to treat cancer. Recently, “immunotherapy” has attracted attention as the fourth treatment. We previously performed fundamental studies using NK cells, one cell type that has attracted attention in immunotherapy, and revealed that the surface CD５６ antigen on the KHYG‐１ human NK cell-like cultured cells as a substitute for human NK cells can be used as an evaluation index of NK cell activity as in human NK cells. We also reported that the cytotoxicity of KHYG‐１increases by IL‐２ stimulation. In this study, we improved the conventional cytotoxicity measurement method to evaluate the effects of a small amount of activator on NK cells. As a result, the cytotoxicity rate and measurement sensitivity at low-concentration IL‐２ stimulation were increased, and it became possible to evaluate the effects of a smaller amount of the activator. In the dynamic observation of KHYG‐１ intracellular granules, it was possible to observe in real time how the target cells were damaged after the influx of granules. Furthermore, the relationship between the activation of KHYG‐１and the change in the intracellular expression level of granzyme B by IL‐２stimulation was clarified, and future research tasks were shown

Simvastatin represses translocation of Pseudomonas aeruginosa across Madin-Darby canine kidney cell monolayers

Pseudomonas aeruginosa causes both invasive (bacteremic) and chronic noninvasive infections. An increase in intestinal epithelial permeability is a characteristic of severe sepsis. Alterations in the normal barrier function of the gut mucosa may result in the translocation of microbial cells and products. On the otherhand, it has been demonstrated that statin use is associated with a lower risk of mortality from bloodstream infections. Therefore, we investigated the ability of P. aeruginosa PAO1 to translocate across the Madin-Darby canine kidney (MDCK) cell monolayers in the presence and absence of simvastatin. The bacteria readily translocated across MDCK cell monolayers after 3 h of infection irrespective of the presence or absence of the drug in the medium. However, the bacteria were less able to penetrate the MDCK monolayers in the presence of simvastatin than in its absence. A gentamicin survival assay demonstrated that simvastatin did not affect the bacteria’s invasive behavior in the MDCK cells

サイキン カンセンショウ カンジャ ニオケル スタチン ノ タメンテキ コウカ

Statins, treatments for dyslipidemia, have been reported to possess effects leading to the repair of the vascular endothelium, as well as anti-oxidative and anti-inflammatory effects, and their clinical usefulness has been focused on. It was also reported in previous clinical research that bacteremia patients on statins showed a lower mortality compared to those not receiving statins, and atherosclerosis patients on statins showed a significantly lower rate of severe or fatal sepsis compared to those not receiving them. We conducted a case-control study involving patients hospitalized in Tokushima University Hospital to evaluate the relationship between taking／not taking statins and bacterial infectious diseases. As a result, there was no relationship between taking／not taking statins and the overall patients with bacterial infectious diseases, but sepsis patients on statins showed a significantly lower mortality. The taking of statins was suggested to be useful for patients with bacterial infectious diseases, particularly males

Maackiain Suppresses H1R and IL-4 Gene Transcriptions

Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)‐4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin‐derived antiallergic compound and investigate its mechanism of action. The H1R and IL‐4 mRNA levels were determined by real‐time quantitative RT‐PCR. To investigate the effects of maackiain in vivo, toluene‐2,4‐diisocyanate (TDI)‐sensitized rats were used as a nasal hypersensitivity animal model. We identified (−)‐maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL‐4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (−)‐Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr311 on PKCδ, which led to the suppression of H1R gene transcription. However, (−)‐maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI‐induced upregulations of H1R and IL‐4 gene expressions in TDI‐sensitized rats. These data suggest that (−)‐maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI‐sensitized allergy model rats through the inhibition of H1R and IL‐4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation