Pharmacognostic Studies on Ginger and Related Drugs (part 2): Constituents of Zingiberis Processum Rhizome (Kankyo)

Nineteen compounds has been isolated from the 80% methanolic extract of Kankyo (Japanese name for Zingiberis processum rhizome) made out of ginger, including a glucoside of 6－gingerdiol (15), four diarylheptanoids (16-19) and the sulfonated compounds such as 6－gingesulfonic acid (10) and shogasulfonic acid A (12) previously reported, besides twelve known compounds. This is the first isolation of compounds 15-19 from the Kankyo. In addition, interestingly, two kinds of Kankyo are found to be sold in the Japanese market: one contains sulfonated derivatives and the other contains no such compound

Effects of Cinnamomi Cortex on the production of allergic and inflammatory mediators in RBL-2H3 and RAW264 cells

桂皮（ケイヒ）は日本薬局方に収載される生薬で，抗アレルギーや解熱鎮痛炎症薬とみなされる漢方処方に配剤される．我々はケイヒの抗アレルギー作用および抗炎症作用について調査し，活性成分の同定を行った．ケイヒを70%メタノールで抽出し（Cin70M），シリカゲルカラムクロマトグラフィー（CC）およびオクタデシルシリルCCを用いて成分を分離した．分離した画分はin vitroでの実験としてラット好塩基球性白血病細胞株（RBL-2H3）およびマウスマクロファージ細胞株（RAW264）を用い，それらが産生するサイトカインmRNAの発現率によって抗アレルギーおよび抗炎症活性を示す画分を明らかにした．また，抗アレルギー作用においては，RBL-2H3の脱顆粒率を測定するために細胞培養液中のβ - ヘキソサミニダーゼも測定した．Cin70Mとシンナムアルデヒド（CNMA）はRBL-2H3細胞における脱顆粒およびインターロイキンのmRNA発現を阻害した．CNMAは300μMで脱顆粒を抑制し，その抑制作用はポジティブコントロールとして用いたケトチフェンより僅かに強かった．同様にCin70MとCNMA はRAW264が産生した一酸化窒素（NO）および炎症性サイトカインmRNA発現を抑制した．特にNO産生についてはCNMA 100μMで10μMのデキサメタゾンと同等の抑制作用を示した．ケイヒの特徴である甘い味と芳香は明らかにした活性成分の一つであるCNMAに由来する．今回の結果から，アレルギー疾患や炎症性疾患の患者に対し，ケイヒを含む漢方薬が処方された際には甘い味と芳香が強いケイヒを選んだ方が良いことが示された．Cinnamomi Cortex (cinnamon bark) is a major crude drug. In Japan, it is used in Kampo medicine to treatallergic and inflammatory diseases. In this study, we examined the anti-allergic and anti-inflammatoryeffects of Cinnamomi Cortex and attempted to identify its active components. Cinnamomi Cortex wasextracted with 70% methanol (Cin70M) and separated into fractions via silica gel column chromatography(CC) or octadecylsilan (ODS) CC. In order to select fractions that have anti-allergic and anti-inflammatoryactivities, we evaluated the ability of the fractions to inhibit the expression of cytokine genes in vitro byusing a rat basophilic leukemia (RBL-2H3) cell line and mouse macrophage (RAW264) cell line. Geneexpression levels were assessed in both cell lines by using semi-quantitative reverse transcriptionpolymerase chain reaction (RT-PCR), and the RBL-2H3 degranulation ratio was quantified via ???? -hexosaminidase assay. Cin70M and cinnamaldehyde (CNMA) inhibited degranulation and the mRNAexpression of interleukins in RBL-2H3 cells. CNMA inhibited degranulation at 300 ????M, and its inhibitoryeffects were slightly stronger than those of ketotifen which is a typical anti-allergic drug. In RAW264 cells,nitric oxide (NO) production and the mRNA expression of inflammatory cytokines were reduced byCin70M and CNMA. In the NO production assay, 100 ????M CNMA was found to significantly decrease NOproduction from activated RAW264 cells, and its activity was the same as that of 10 ????M dexamethasone.The taste and scent of Cinnamomi Cortex were both attributed to CNMA. The results of the presentstudy indicate that it is more beneficial for patients with allergic and/or inflammatory diseases to useCinnamomi Cortex with a strong taste and scent

Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder

Altered Network Topologies and Hub Organization in Adults with Autism: A Resting-State fMRI Study

<div><p>Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of “hubness” in several nodes (e.g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC.</p></div

Hub nodes identified using the bootstrap method.

<p>The first row shows five NC-specific hubs (A), the second row shows six ASC-specific hubs (B), and the last row shows four common hubs (C). Hub distribution was visualized with the BrainNet Viewer (<a href="http://www.nitrc.org/projects/bnv/" target="_blank">http://www.nitrc.org/projects/bnv/</a>). Correspondences between colors and networks are as follows: fronto-parietal = red; cingulo-opercular = green; default mode = blue; occipital = cyan; sensorimotor = magenta.</p

Between-group differences in the AUC values of assortativity, <i>r</i>; clustering coefficient, <i>C</i>; characteristic path length, <i>L</i>; and small-worldness scalar, σ.

<p>In the AUC analyses, participants in the ASC group (black) also showed significantly lower <i>r</i> (<i>p</i> = 0.013) (A), <i>C</i> (<i>p</i> = 0.014) (B), and <i>L</i> (<i>p</i> = 0.002) (C) than those in the NC group (white), whereas there were no significant differences in the small-worldness scalar σ (D) between the groups. The error bar indicates the standard error of the mean (SEM). Significance levels are represented by *<i>p</i><0.05 and **<i>p</i><0.01, respectively.</p

The number of affected nodes (NC>ASC or ASC>NC) and non-affected nodes.

†<p>The numbers in parentheses indicate the number of nodes in each sub-network.</p>††<p>The percentages in parentheses indicate the proportion of affected (or non-affected) nodes to the total number of nodes in each sub-network.</p><p>FP: fronto-parietal, CO: cingulo-opercular, DEF: default-mode, OC: occipital, SE: sensorimotor, CER: cerebellar.</p

Altered local metrics of degree; betweenness; and nodal efficiency.

<p>Alterations in each of local metrics, including degree (A), betweenness (B), and nodal efficiency (C), were observed. The red sphere indicates NC>ASC, while the blue sphere denotes ASC>NC. Of note, in this study, the right inferior temporal [52, −15, −13] was regarded as the right superior temporal sulcus (STS), because this node was anatomically located on the STS rather than the inferior temporal. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094115#pone.0094115.s011" target="_blank">Table S3</a> for other nodes re-labeled in this study. The distributions of nodes showing altered local metrics were visualized with the Brain Net Viewer (<a href="http://www.nitrc.org/projects/bnv/" target="_blank">http://www.nitrc.org/projects/bnv/</a>).</p