Biological Activities and Applications of Dioscorins, the Major Tuber Storage Proteins of Yam

AbstractYam tubers, a common tuber crop and an important traditional Chinese medicine in Taiwan, have many bioactive substances, including phenolic compounds, mucilage polysaccharides, steroidal saponins and proteins. Among the total soluble proteins, 80% of them are dioscorins. In the past two decades, many studies showed that dioscorins exhibited biological activities both in vitro and in vivo, including the enzymatic, antioxidant, antihypertensive, immunomodulatory, lectin activities and the protecting role on airway epithelial cells against allergens in vitro. Some of these activities are survived after chemical, heating process or enzymatic digestion. Despite of lacking the intact structural information and the detail action mechanisms in the cells, yam dioscorins are potential resources for developing as functional foods and interesting targets for food protein researchers

Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review of Clinical Trials

The therapeutic potentials of probiotics in autism spectrum disorder (ASD) remains controversial, with the only existing systematic review on this topic published in 2015. Results from new trials have become available in recent years. We therefore conducted an updated systematic review, to assess the efficacy of probiotics in relieving behavioral symptoms of ASD and gastrointestinal comorbidities. Our review includes two randomized controlled trials, which showed improvement of ASD behaviors, and three open trials, all which exhibited a trend of improvement. Four of these trials concluded from subjective measures that gastrointestinal function indices showed a trend of improvement with probiotic therapy. Additional rigorous trials are needed to evaluate the effects of probiotic supplements in ASD

(+)-Vitisin A Inhibits Osteoclast Differentiation by Preventing TRAF6 Ubiquitination and TRAF6-TAK1 Formation to Suppress NFATc1 Activation

<div><p>We recently reported that oral administration of a (+)-vitisin A-enriched product prepared from <i>Vitis thunbergii</i> obviously ameliorated bone loss in ovariectomized mice and (+)-vitisin A was able to inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells. Here we further clarified the mechanism(s) by which (+)-vitisin A targets osteoclastic differentiation and activity. Osteoclast-characteristic enzyme activity was determined using gel zymography or spectroflurometric-based assay. Expression of signal molecules was analyzed via Western blot or immunoprecipitation. Results showed that (+)-vitisin A suppressed RANKL-induced multinuclear cells (MNCs) formation and bone resorption which was accompanied with reduction in β3 integrin, osteoclast stimulatory transmembrane protein (OC-STAMP), matrix metalloproteinase-9 (MMP-9) and cathepsin K proteins expression. (+)-Vitisin A also down-regulated the proteolytic activities of MMP-9 and cathepsin K via targeting at the late stage function. (+)-Vitisin A prominently abrogated RANKL-triggered nuclear translocations of NF-κB, AP-1 (c-Fos/c-Jun dimer) and associated induction and nuclear accumulation of nuclear factor of activated T cells c1 (NFATc1). The upstream IκB degradation as well as ERK and JNK phosphorylation were also substantially repressed. Transfection with siRNA targeting tumor necrosis factor receptor associated factor 6 (TRAF6) clearly restrained RANKL-induced MNCs formation and NFATc1 induction. Interesting, RANKL triggered poly-ubiquitination of TRAF6 and associated TRAF6-TAK1 (transforming growth factor β-activated kinase 1) complex formation was prominently attenuated by (+)-vitisin A. Furthermore, the interaction between c-src tyrosine kinase (c-Src) and β3 was markedly induced by RANKL stimulation. (+)-Vitisin A significantly attenuated this interaction when concomitant treated with RANKL in RAW264.7 cells, but failed to affect c-Src/β3 complex formation when post-cultured with MNCs. Taken together, (+)-vitisin A suppressed bone resorption possibly via interruption of RANKL-induced TRAF6 ubiquitination and associated downstream signaling pathways. Furthermore, action through negative regulation of the proteolytic activity of MMP-9 and cathepsin K might also contribute to the anti-resorption effect of (+)-vitisin A.</p></div

Protective Effects of Antrodia Cinnamomea Against Liver Injury

Chinese herbal medicine (中草藥) attracts much attention in the treatment of liver injuries. Numerous studies have revealed various biological activities of medicinal mushrooms such as Antrodia Cinnamomea (牛樟芝). Although A. cinnamomea is rare in the wild, recent developments in fermentation and cultivation technologies make the mycelia and fruiting bodies of this valuable medicinal mushroom readily available. Liver diseases such as fatty liver, hepatitis, hepatic fibrosis, and liver cancer are complicated processes of liver injuries that have tremendous impact on human society. In this article, we reviewed studies about the hepatoprotective effects of the fruiting bodies and mycelia of A. cinnamomea performed in different experimental models. The results of those studies suggest the potential application of A. cinnamomea in preventing and treating liver diseases and its potential to be developed into health foods or new drugs

RANKL-stimulated NFATc1 induction and translocation.

<p>The (A) induction and (B) nuclear translocation of NFATc1 by RANKL stimulation were suppressed by (+)-vitisin A (Vt-A). RAW264.7 macrophages were stimulated with RANKL (100 ng/mL) for 48 h in the absence or presence of Vt-A then the total and nuclear protein were extracted as described in methods. Results are expressed as the mean ± SEM for each group from four to five separate experiments normalized for histone (for nuclear protein normalization) or β-actin (for total protein normalization) respectively. *p< 0.05, **p< 0.01 and ***p< 0.001, different from values after stimulated with RANKL alone.</p

(+)-Vitisin A (Vt-A) suppressed RANKL-induced expression of β3 integrin, OC-STAMP, MMP-9 and cathepsin K in RAW264.7 cells.

<p>The relative protein levels were measured by western blot and normalized to β-actin. Data represent the mean ± SEM of at least three independent experiments. *p<0.05, **p<0.01 and ***p< 0.001, different from values after stimulated with RANKL alone.</p

(+)-Vitisin A (Vt-A) suppressed the accumulation of ubiquitinated TRAF6 and the association of TRAF6-TAK1 complex.

<p>(A) RAW264.7 cells were stimulated with RANKL in the absence or presence of (+)-vitisin A. After incubation, cell lyses were immunoprecipitated with anti-TRAF6 antibody. Bound proteins were further immunoblotted with anti-ubiquitin or anti-TRAF6 antibody. (B) Cell extracts were immunoprecipitated with anti-TAK1 antibody. Bound proteins were further immunoblotted with anti-TRAF6 or anti-TAK1 antibody. Results are expressed as the mean ± SEM for each group from three to four separate experiments. *p<0.05, **p<0.01 and ***p<0.001, different from values after treatment with RANKL alone.</p

Proposed intracellular mechanisms of (+)-vitisin A in suppressing RANKL-induced osteoclastogenesis in RAW264.7 cells.

<p>The underlying mechanisms involved interfering with the ubiquitination of TRAF6 and downstream signaling cascades to suppression the expression of osteoclast marker proteins and bone resorption. Furthermore, down-regulation of matrix-degrading enzymes activity (cathepsin K and MMP-9) by (+)-vitisin A might also contribute to the beneficial effect on preventing bone loss. AP-1, activator protein 1; DC-STAMP, dendritic cell-specific transmembrane protein; MAPKs, mitogen-activated protein kinases; MITF, microphthalmia-associated transcription factor; MMP-9, matrix metalloproteinase-9; NFATc1, nuclear factor of activated T cells c1; RANKL, receptor activator of nuclear factor κB (NF-κB) ligand; TAK1, transforming growth factor β-activated kinase (TAK)-1; TRAF6, tumour necrosis factor receptor-associated factor 6.</p