Young-Ji Shiao

National Research Institute of Chinese Medicine · Division of Basic Chinese Medicine

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aging is a natural human process. It is uniquely individual, taking into account experiences, lifestyle habits and environmental factors. However, many disorders and syndromes, such as osteoporosis, neurodegenerative disorders, cognitive decline etc., often come with aging. The present study was designed to investigate the possible anti-aging effec...

Multitarget agents simultaneously trigger molecules in functionally complementary pathways, and are therefore considered to have potential in effectively treating Alzheimer's disease (AD), which has a complex pathogenetic mechanism. In this study, the HDAC inhibitor core is incorporated into the acetylcholine esterase (ACE) inhibitor acridine–deriv...

Alzheimer’s disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD...

High-fat and high-sugar diets contribute to the prevalence of type 2 diabetes and Alzheimer's disease (AD). Although the impact of high-fat diets on AD pathogenesis has been established, the effect of high-sucrose diets (HSDs) on AD pathogenesis remains unclear. This study sought to determine the impact of HSDs on AD-related pathologies. Male APPsw...

Activated epidermal growth factor receptor (EGFR) has been proposed in the pathophysiology of neurodegenerative diseases. In the present study, the anti-inflammatory effect of afatinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKIs) was investigated using CTX-TNA2 cells and primary cultured astrocytes subjected to oxygen/glucose deprivation (OGD). W...

Ischemic stroke is one of the most common causes of death worldwide and is a major cause of acquired disability in adults. However, there is still a need for an effective drug for its treatment. Buyang Huanwu decoction (BHD), a traditional Chinese medicine (TCM) prescription, has long been used clinically to aid neurological recovery after stroke....

344 proteins were quantitated from CSF. (XLSX)

PANTHER analysis of proteins differentially expressed between CI/R-induced and control mice. (A) GO analysis of selected proteins in terms of cellular component (protein location). (B) PANTHER analysis of selected proteins in terms of molecular function. (C) PANTHER analysis of selected proteins in terms of biological process. (D) PANTHER analysis...

Quantitation of BHD-responsive metabolites in CSF by LC-QTOF-MS. (A) Metabolites with increased expression in the CI/R group and reversed with BHD treatment. (B) Metabolites with reduced expression in the CI/R group and reversed with BHD treatment. CIR: CI/R group; C+B: CI/R+BHD group. *P < 0.05, **P < 0.01 compared with the control group. #P < 0.0...

Details of method and materials and methods. (DOC)

The representative chemical fingerprint of BHD by UPLC. UPLC chromatogram was carried out on a Thermo Syncronis C18 column (2.1 mm×100 mm i.d., 1.7 μm) in Waters Acquity UPLC system with a diode array detector (DAD), monitor at 203, 230, and 280nm. The mobile phase was 0.1% phosphate water (A) and acetonitrile (B) with a program of 2% B at 0–1 min,...

Functional enrichment analysis of the differentially expressed proteins. The y‑axis shows significantly enriched Gene Ontology (GO) terms relative to the genome, and the x-axis shows the fold enrichment of these terms. Red bars, “Molecular Function” categories in GO; green bars, “Cellular Component” categories in GO; gray bars, “Biological Process”...

Metabolites changes among sham, CI/R and BHD groups. Scatter plots of scores of (A) PCA, (B) PLS-DA, and (C) OPLS-DA, obtained, respectively to the LC-QTOF-MS of CSF from sham (blue), CI/R (green), CI/R+BHD group (red). (D) Loading plot of OPLS-DA among sham, CI/R and BHD groups. (TIF)

Ethyl 8-hydroxy-4-methoxyquinoline-2-carboxylate (1) and a new compound, erinacerin U (2), were isolated from the mycelia of Hericium erinaceum. Their structures were elucidated by spectroscopic analysis. Compound 1 was found to possess a significant inhibition on the production of NO in LPS-activated microglia.

Hericium erinaceus , an ideal culinary-medicinal mushroom, has become a well-established candidate in promoting positive brain and nerve health-related activities by inducing the nerve growth factor from its bioactive ingredient. Among its active compounds, only erinacine A has confirmed pharmacological actions in the central nervous system in rats...

Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoi...

Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine th...

Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis rema...

Ethnopharmacological relevance: Metabolic syndrome and vascular dysfunction was suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu decoction (XZD) is a traditional Chinese medicine used to treat metabolic syndrome and cardiac-cerebral vascular disease. The effects of XZD on ameliorating metabolic syndrome, amyloid-related p...

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the...

Echinacoside is a phenylethanoid glycoside and possesses neuroprotective activity in vitro and in vivo. This study investigates the role of amyloid cascade and central neuronal function on the protective effects of echinacoside in amyloid β peptide 1-42 (Aβ 1-42)-treated SH-SY5Y cells and Aβ 1-42-infused rat. Echinacoside inhibited Aβ 1-42 oligomer...

The drugs currently used to treat Alzheimer's disease (AD) are limited in the benefits they confer, and no medication has been clearly proven to cure or delay the progression of AD. Most candidate AD drugs are meant to reduce the production, aggregation, and toxicity of amyloid β (Aβ) or to promote Aβ clearance. Herein, we demonstrate the efficient...

Acteoside and isoacteoside, two phenylethanoid glycosides, coexist in some plants. This study investigates the memory-improving and cytoprotective effects of acteoside and isoacteoside in amyloid β peptide 1-42 (Aβ 1-42)-infused rats and Aβ 1-42-treated SH-SY5Y cells. It further elucidates the role of amyloid cascade and central neuronal function i...

The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer’s disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAβ clearance by microglia whil...

Background The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer’s disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer’s disease remains unclear. In this study, the effects of erinacine A-enriched Herici...

A new sesterterpene, erinacine S, and one cyathane diterpene xyloside, erinacine A, were isolated from the ethanol extract of the mycelia of Hericium erinaceus. Their structures were elucidated by spectroscopic and X-ray analysis. A 30-day oral course of erinacines A and S attenuated Aβ plaque burden in the brains of 5-month-old female APP/PS1 tran...

Eight new clausenamides, including three γ-lactams (1-3), four δ-lactams (4-7), and an amide (8), and seven known lactams, including compounds 9-11, which were purified from natural sources for the first time, were characterized from the leaves of Clausena lansium. Their structures were elucidated using spectroscopic methods, and the absolute confi...

Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA) is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we char...

Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated w...

Although metabolic syndrome was suggested to be a risk factor for Alzheimer's disease (AD), the role of metabolic stress in the initiation of AD pathology remains unclear. In this study, metabolic stress was induced by a high-fat diet and low-dose injection of streptozotocin (HFSTZ) before the appearance of senile plaques in APP/PS1 transgenic mice...

Background Parkinson’s disease is the second most common neurodegenerative disorders after Alzheimer’s disease. The main cause of the disease is the massive degeneration of dopaminergic neurons in the substantia nigra. Neuronal apoptosis and neuroinflammation are thought to be the key contributors to the neuronal degeneration. Results Both CATH.a...

Background: The roles of caspase 3 on the kainic acid-mediated neurodegeneration, dendritic plasticity alteration, neurogenesis, microglial activation and gliosis are not fully understood. Here, we investigate hippocampal changes using a mouse model that receive a single kainic acid-intracerebral ventricle injection. The effects of caspase 3 inhib...

The specific role of microglia on Abeta-mediated neurotoxicity is difficult to assign in vivo due to their complicated environment in the brain. Therefore, most of the current microglia-related studies employed the isolated microglia. However, the previous in vitro studies have suggested either beneficial or destructive function in microglia. There...

Background: Insufficient clearance of soluble oligomeric amyloid-β peptide (oAβ) in the central nervous system leads to the synaptic and memory deficits in Alzheimer's disease (AD). Previously we have identified scavenger receptor class A (SR-A) of microglia mediates oligomeric amyloid-β peptide (oAβ) internalization by siRNA approach. SR-A is a m...

Microglial inflammation may significantly contribute to the pathology of Alzheimer's disease. To examine the potential of Cudrania cochinchinensis to ameliorate amyloid beta protein (Abeta)-induced microglia activation, BV-2 microglial cell line, and the ramified microglia in the primary glial mixed cultured were employed. Lipopolysaccharide (LPS),...

Flemingia macrophylla (Leguminosae) is a popular traditional remedy used in Taiwan as anti-inflammatory, promoting blood circulation and antidiabetes agent. Recent study also suggested its neuroprotective activity against Alzheimer's disease. Therefore, the effects of F. macrophylla on Aβ production and degradation were studied. The effect of F. ma...

The accumulation of soluble oligomeric amyloid-β peptide (oAβ) proceeds the formation of senile plaques and contributes to synaptic and memory deficits in Alzheimer's disease (AD). The mechanism of mediating microglial oAβ clearance remains unclear and thought to occur via scavenger receptors (SRs) in microglia. SRs respond to their ligands in a su...

Overactivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD). Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that med...

Time-lapse recording of migratory motion of control BV-2 microglia.

Time-lapse recording of migratory motion of BV-2 microglia treated with aggregated FAM-labeled Aβ.

Time-lapse recording of migratory motion of BV-2 microglia treated with TGF-β1.

Time-lapse recording of migratory motion of BV-2 microglia treated with TGF-β1 and aggregated FAM-labeled Aβ.

Three new polyphenolic compounds including a dihydrophenanthrene, pleioanthrenin (1), two bibenzyls, pleiobibenzynin A (2) and B (3), and a new cycloartane triterpenoid, (24R)-cyclomargenyl p-coumarate (4), together with eight known compounds, were isolated from the pseudobulbs of Pleione formosana. The structures of the new compounds were elucidat...

The number of microglia surrounding senile plaques is correlated with the size of plaques in Alzheimer's disease (AD). It is unclear whether more microglia are passively recruited toward larger senile plaques or, conversely, microglia recruited to senile plaques directly contribute to the growth of plaques. In this study, BV-2 microglia were used t...

The effect of tournefolic acid B (TAB) on amyloid beta protein-mediated neurotoxicity and the underlying mechanisms were investigated. Amyloid beta protein 25-35 elicited neuronal death as determined by calcein/ethidium homodimer-1 staining. 10 microM amyloid beta protein 25-35 caused cell death at a level of 41.5+/-3.8% by MTT reduction. 50 microM...

A series of phenylazobenzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB) and an enzymatic assay using purified ovine enzymes. Extensive structure-activity relationships (SAR) were studied within this series, and several of...

Three new compounds, 19-hydroxylabda-8(17)-en-16,15-olide (1), 3beta,19-dihydroxylabda-8(17),11E-dien-16,15-olide (2), and 13-epi-3beta,19-dihydroxylabda-8(17),11E-dien-16,15-olide (3), together with four known compounds, 19-hydroxylabda-8(17),13-dien-16,15-olide (4), 14-deoxy-11,12-didehydroandrographolide (5), 14-deoxyandrographolide, and pinusol...

The effects of tournefolic acid B (TAB) and two ester derivatives, TAB methyl ester (TABM) and TAB ethyl ester (TABE), on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity and the underlying mechanisms were investigated. Treatment with 50 microM NMDA elicited neuronal death by 48.7 +/- 5.1%, coinciding with the appearance of injured morphology. T...

Activation of hepatic stellate cells (HSCs) is a key feature of liver fibrosis. During the development of hepatic fibrosis, activated HSCs are the primary source of extracellular matrix. Induction of HSC apoptosis has been proposed as one of therapeutic strategies for this desease. Ligusticum chuanxiong (LC) is a traditional Chinese herb that has b...

Using an Abeta-induced neurotoxicity blocking assay to direct fractionation, three new flavonoids, fleminginin (1), flemingichromone (2), and flemingichalcone (3), and twenty known compounds were isolated from the active fractions of the aerial parts of Flemingia macrophylla. The structures of 1 - 3 were elucidated on the basis of spectroscopic dat...

The effects of nine polyphenolic compounds on glutamate-mediated toxicity were investigated. The underlying mechanisms by which a polyphenolic compound confers its effect were also elucidated. Treatment of cortical neurons with 50 microm glutamate for 24 h decreased cell viability by 45.8 +/- 7.9%, and 50 microm of tournefolic acid B methyl ester a...

The effects of falcarindiol on the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) in rat primary astrocytes were investigated. The molecular mechanisms underlying falcarindiol that confers its effect on iNOS expression were also elucidated. Falcarindiol abrogated the LPS/IFN-gamma...

Nitric oxide (NO) is a free radical synthesized from L-arginine by three isoforms of NO synthase (NOS). NO is involved in a wide range of physiological functions. It functions as neurotransmitter by modulating the release of glutamate and the neurotransmission of N-methyl- D-aspartate (NMDA) receptor, as neuro-endothelial-derived relaxing factor th...

Phenylazo benzenesulfonamides were designed and synthesized as beta-amyloid (Abeta40) fibril assembly inhibitors, and evaluated for inhibition of Abeta40 aggregation and neurotoxicity using rat cortical neurons. Compound 2 (LB-152) was the most potent compound in this study, and the para-NMe(2) group on the end of the phenylazo moiety may play an i...

A new dihydrobenzodioxane derivative, origalignanol (10), together with nine polyphenolic compounds, salvianolic acid A (1), salvianolic acid C (2), lithospermic acid (3), apigenin 7-O-β-D-glucuronide (4), apigenin 7-O-β-D-(6″-methyl)glucuronide (5), luteolin, (6), luteolin 7-O-β-D-glucopyranoside (7), luteolin 7-O-β-D-glucuronide (8), and luteolin...

Moscatilin and a series of bibenzyl derivatives were synthesized from appropriate aromatic aldehydes and phosphonium salts through the Wittig reaction. The antioxidative and cytotoxic activities of these bibenzyl derivatives were evaluated.

Amyloid β protein (Aβ) elicits a toxic effect on neurons in vitro and in vivo and has been proposed to play an important role in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that aggregated Aβ can induce caspase-dependent apoptosis by oxidative stress in cultured neurons. Uncaria rhynchophylla (miq.) Jacks., a tradition...

The effects of polyacetylenes on the activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide/interferon-γ (LPS/IFN-γ) in rat primary astrocytes were investigated. The mechanisms underlying how polyacetylenes confer their effects on iNOS activity were also elucidated. Five polyaceylenes differentially abrogated the LPS/IFN-γ...

A new dihydrobenzodioxane derivative, origalignanol (10), together with nine polyphenolic compounds, salvianolic acid A (1), salvianolic acid C (2), lithospermic acid (3), apigenin 7-O-beta-D-glucuronide (4), apigenin 7-O-beta-D-(6"-methyl)glucuronide (5), luteolin, (6), luteolin 7-O-beta-D-glucopyranoside (7), luteolin 7-O-beta-D-glucuronide (8),...

Senile plaques and neurofilament tangles are the hallmarks of Alzheimer's disease (AD). Amyloid β protein (Aβ), the major protein component of senile plaques, has been suggested to play an important role in the pathogenesis of AD. Aβ is proteolytically derived from amyloid precursor protein, which is widely expressed throughout the brain. Multiple...

In view of the facts that ginseng has been shown to improve age-related memory deficits and beta-amyloid-related peptides have been suggested to play a significant role in memory degeneration in the elderly, the present study was carried out to examine the effect of various ginsenosides on beta-amyloid peptides-modulated acetylcholine (ACh) release...

This study examined the effectiveness of health promotion counseling for overweight adolescent nursing students. The Chinese version of an established health promotion counseling booklet developed by the author of this study was used in the counseling. The study employed a one-group pre- and post-quasi-experimental research design from September 19...

Amyloid beta protein (Abeta) elicits a toxic effect on neurons in vitro and in vivo. In present study we attempt to elucidate the mechanism by which Abeta confers its neurotoxicity. The neuroprotective effects of phytoestrogens on Abeta-mediated toxicity were also investigated. Cortical neurons treated with 5 microm Abeta-(25-35) for 40 h decreased...

A series of polyacetylenes, falcarinone, panaxynol, falcarindiol, panaxydol, and panaxytriol, were isolated from Saposhnikovia divaricata (Turcz.) Schischk and Panax quinquefolium L. These polyacetylenes were identified as active principles on the inhibition of nitrite production by inducible nitric oxide synthase (iNOS). Treatment with 10 microM o...

The effects of nepalolide A on the expression of inducible nitric oxide synthase (iNOS) caused by incubation with lipopolysaccharide/interferon-γ (LPS/IFN-γ) or tumour necrosis factor-α/interleukin-1β/IFN-γ (TNF-α/IL-1β/IFN-γ, mixed cytokines) in C6 glioma cells and primary astrocytes of rat were investigated. The mechanisms by which nepalolide A c...

The mechanism of import of phosphatidylserine (PtdSer) into mitochondria was investigated using a reconstituted system of isolated organelles in vitro in which PtdSer was translocated from donor membranes to mitochondria and was decarboxylated therein. Neither phosphatidylcholine nor phosphatidylethanolamine (PtdEtn) was translocated under the same...

Three mechanisms are commonly suggested for the movemerlt of lipids between intracellular organelles: transfer mediated by cytosolic lipid transfer proteins, vesicle-mediated transfer, and transfer via regions of membrane continuity between organelles. The mechanism of translocation of phosphatidylserine from its site of synthesis on the endoplasmi...

Evidence is presented for the operation of an ethanolamine-phosphatidylethanolamine (PtdEtn) cycle in Chinese hamster ovary cells. PtdEtn was labelled with [3H]ethanolamine and radioactivity was chased by incubation with 1 mM unlabelled ethanolamine. Radioactivity in [3H]PtdEtn gradually declined over a 23 h time period. In contrast, when the cells...

Phosphatidylserine is synthesized in both the endoplasmic reticulum and a unique membrane fraction, the mitochondria-associated membrane (MAM) (Vance, J.E. (1990) J. Biol. Chem. 265, 7248-7256). In Chinese hamster ovary cells labeled with [3H]serine or [3H]ethanolamine, we found that the majority of mitochondrial phosphatidylethanolamine was derive...

The transport of sphingomyelin from its site of synthesis, in the cis/medial-Golgi, to the plasma membrane has been investigated in monolayer cultures of rat hepatocytes. Sphingomyelin was synthesized intracellularly from [methyl-3H]choline, and the arrival of sphingomyelin at the plasma membrane was monitored by treatment of the cells with sphingo...

Cholate and its conjugated amide derivatives glycocholate and taurocholate solubilized human platelets differently as studied by the observations on: (1) the change in optical absorbance of platelet suspension, (2) marker leakiness and (3) component solubility. Cholate ruptures the membrane in an all-or-none process, while both conjugated derivativ...

The solubilization of human gel-filtered platelets by octyl glucoside, Triton X-100, dodecylsulfate, and deoxycholate was compared from the analysis of (1) cell lysis, (2) marker leakiness, and (3) component solubility. These analyses all revealed that the effect of detergent concentration on the solubilization of platelets by these detergents was...

TFP is a lipophilic antipsychotic drug. The drug will first encounter with cell membrane when adding it into a cell suspension. The effect of TFP on plasma membrane of the gel-filtered human platelet was investigated by : 1) scanning electron microscopy (SEM); 2) measuring theleakiness of marker enzymes and compound; 3) estimating its solubility in...

the morphological sthudy by scanning electron microscopy (SEM) showed that blebs were found on cell surface of the gel-filtered human platelets when incubated in the modified Tyrode's buffer containing 8mM or higher of Ca++ for 5 min. EDTA immediately abolished blebs [Wang et al Thrombos. Haemostas., 54, 184 (1985)]. The phenomenon was further inve...

On the membrane surface of the human platelet, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were hydrolyzed to different extents by the snake venom phospholipases A2 of varying pI values. The susceptibility of platelet phospholipids to basic phospholipase A2 of Naja nigricollis (pI 10.6) has been reported (Wang et al. (1986) Biochim....

Human platelets in three physiological states were prepared. These states were the gel-filtered, the thrombin-induced shape-changed, and the thrombin-activated platelets. The phospholipid distributions in these three types of membrane were probed by using the basic phospholipase A2 of Naja nigricollis. This enzyme could penetrate through these memb...