Publications by authors named "Yi-Fan Han"

59 Publications

Combination of Trace Metal to Improve Solventogenesis of P7 in Syngas Fermentation.

Front Microbiol 2020 25;11:577266. Epub 2020 Sep 25.

Tianjin Key Laboratory for Industrial Biological Systems and Bioprocessing Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Higher alcohols such as butanol (C4 alcohol) and hexanol (C6 alcohol) are superior biofuels compared to ethanol. P7 is a typical acetogen capable of producing C4 and C6 alcohols natively. In this study, the composition of trace metals in culture medium was adjusted, and the effects of these adjustments on artificial syngas fermentation by P7 were investigated. Nickel and ferrous ions were essential for growth and metabolite synthesis during syngas fermentation by P7. However, a decreased dose of molybdate improved alcohol fermentation performance by stimulating carbon fixation and solventogenesis. In response to the modified trace metal composition, cells grew to a maximum OD of 1.6 and accumulated ethanol and butanol to maximum concentrations of 2.0 and 1.0 g/L, respectively, in serum bottles. These yields were ten-fold higher than the yields generated using the original composition of trace metals. Furthermore, 0.5 g/L of hexanol was detected at the end of fermentation. The results from gene expression experiments examining genes related to carbon fixation and organic acid and solvent synthesis pathways revealed a dramatic up-regulation of the Wood-Ljungdahl pathway (WLP) gene cluster, the gene cluster, and a putative CoA transferase and butanol dehydrogenase, thereby indicating that both synthesis and acid re-assimilation contributed to the significantly elevated accumulation of higher alcohols. The gene was speculated to be the key target for butanol synthesis during solventogenesis.
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http://dx.doi.org/10.3389/fmicb.2020.577266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546793PMC
September 2020

Structure-Tunable Copper-Indium Catalysts for Highly Selective CO Electroreduction to CO or HCOOH.

ChemSusChem 2019 Sep 5;12(17):3955-3959. Epub 2019 Aug 5.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Selectively approaching chemicals with one composition-tunable catalyst is attractive for practical manufacturing. Bimetallic copper-indium (Cu-In) catalysts have been synthesized by using a coprecipitation method and found to be among the best reported In-based catalysts for electrochemical CO reduction to CO or HCOOH. By varying the metal ratio, the catalyst can be tuned from a core-shell structure that selectively produces CO to a well-mixed structure that prefers HCOOH production. The distinct selectivities depend on the structure-sensitive binding strength of key reactive intermediates. These findings can benefit the development of a broader range of selectivity-tunable catalysts.
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http://dx.doi.org/10.1002/cssc.201901884DOI Listing
September 2019

Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review.

Front Neurosci 2019 9;13:445. Epub 2019 May 9.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.

The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD. The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders. A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded. A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory. The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders.
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http://dx.doi.org/10.3389/fnins.2019.00445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521802PMC
May 2019

Strong Metal-Support Interactions between Copper and Iron Oxide during the High-Temperature Water-Gas Shift Reaction.

Angew Chem Int Ed Engl 2019 Jul 28;58(27):9083-9087. Epub 2019 May 28.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.

The commercial high-temperature water-gas shift (HT-WGS) catalyst consists of CuO-Cr O -Fe O , where Cu functions as a chemical promoter to increase the catalytic activity, but its promotion mechanism is poorly understood. In this work, a series of iron-based model catalysts were investigated with in situ or pseudo in situ characterization, steady-state WGS reaction, and density function theory (DFT) calculations. For the first time, a strong metal-support interaction (SMSI) between Cu and FeO was directly observed. During the WGS reaction, a thin FeO overlayer migrates onto the metallic Cu particles, creating a hybrid surface structure with Cu-FeO interfaces. The synergistic interaction between Cu and FeO not only stabilizes the Cu clusters, but also provides new catalytic active sites that facilitate CO adsorption, H O dissociation, and WGS reaction. These new fundamental insights can potentially guide the rational design of improved iron-based HT-WGS catalysts.
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http://dx.doi.org/10.1002/anie.201903298DOI Listing
July 2019

Visible-Light Photocatalytic Activity of Fe and/or Ni Doped Ilmenite Derived-Titanium Dioxide Nanoparticles.

J Nanosci Nanotechnol 2019 Jun;19(6):3343-3355

State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China.

Pure TiO₂ nanoparticles and ones doped with Fe and/or Ni were successfully prepared by a co-precipitation method from ilmenite. The samples were structurally characterized by XRD, XPS, FT-IR, UV-vis, SEM, EDX, AAS and BET measurement. The XRD results showed that all samples were anatase TiO₂, and no characteristic peaks of dopants were observed. The crystallite sizes of all doped TiO₂ nanoparticles were less than 20 nm and doping TiO₂ with metal ions can suppress the crystal growth of the particles. The XRD and XPS results indicated that TiO₂ was uniformly doped and its crystalline phase was not changed by doping. The specific surface area of Fe-Ni/TiO₂ is bigger than that of the un-doped TiO₂. The pore size and pore volume of Fe-Ni/TiO₂ is smaller than that of the un-doped. UV-vis spectra of the samples showed that the absorption edge red shifted with increasing doped metal content. The photocatalytic activity was evaluated in oxidative degradation of methylene blue (MB) with H₂O₂ under visible light irradiation. When doped with a single type of transition metal, the photocatalytic performance of Ni-doped samples was lower than that of Fe-doped ones. For the co-doped catalysts, the catalytic efficiency of 0.5%Fe₄%Ni/TiO₂ was the highest, reaching 93.34% after 250 min. Metal doping enhanced the photocatalytic decomposition of methylene blue compared with that of pure TiO₂ by up to 1.5 times. The synergistic effects of the two metal ions improved the photocatalytic performance. The particles exhibited pronounced activity in degradation of MB as well as efficient recyclability. The photocatalytic degradation mechanism of methylene blue was analyzed.
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http://dx.doi.org/10.1166/jnn.2019.16123DOI Listing
June 2019

Covalently Grafting Cobalt Porphyrin onto Carbon Nanotubes for Efficient CO Electroreduction.

Angew Chem Int Ed Engl 2019 May 14;58(20):6595-6599. Epub 2019 Feb 14.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China.

Molecular complexes with inexpensive transition-metal centers have drawn extensive attention, as they show a high selectivity in the electrochemical conversion of CO to CO. In this work, we propose a new strategy to covalently graft cobalt porphyrin onto the surface of a carbon nanotube by a substitution reaction at the metal center. Material characterization and electrochemical studies reveal that the porphyrin molecules are well dispersed at a high loading of 10 wt. %. As a result, the turnover frequency for CO formation is improved by a factor of three compared to traditional physically-mixed catalysts with the same cobalt content. This leads to an outstanding overall current density of 25.1 mA cm and a Faradaic efficiency of 98.3 % at 490 mV overpotential with excellent long-term stability. This work provides an effective pathway for the improvement of the performance of electrocatalysts that could inspire rational design of molecular catalysts in the future.
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http://dx.doi.org/10.1002/anie.201900499DOI Listing
May 2019

miR-27b-3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator-Activated Receptor Gamma.

Basic Clin Pharmacol Toxicol 2018 Dec 5;123(6):670-677. Epub 2018 Aug 5.

Department of General Surgery, Anhui Provincial Hospital, Hefei, Anhui, China.

Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumours. To investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells. Targeted inhibition of miR-27b can increase the sensitivity of SW1736/Dox and 8305C/Dox cells. Bioinformatics analysis revealed that miR-27b can directly target peroxisome proliferator-activated receptor gamma (PPARγ) within the 3' untranslated region (UTR). This was proved by the results that miR-27b-3p down-regulated the protein and mRNA levels of PPARγ. While the mutant in the core binding sites of PPARγ abolished miR-27b-3p-induced down-regulation of luciferase activity. Over-expression of PPARγ can increase the Dox sensitivity of SW1736/Dox and 8305C/Dox cells. Basic fibroblast growth factor (bFGF) might be involved in miR-27b-3p/PPARγ-regulated Dox resistance of ATC cells. The activation of p65 nuclear factor-κB (NF-κB) regulated the up-regulation of miR-27b-3p in Dox-resistant ATC cells. Collectively, our data revealed that miR-27b-3p/PPARγ is involved in the Dox resistance of human ATC cells. It suggested that targeted inhibition of miR-27b-3p might be helpful to overcome the drug resistance of ATC cells.
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http://dx.doi.org/10.1111/bcpt.13076DOI Listing
December 2018

Constructions of Unextendible Maximally Entangled Bases in [Formula: see text].

Sci Rep 2018 02 16;8(1):3193. Epub 2018 Feb 16.

School of Mathematics Sciences, Capital Normal University, Beijing, 100048, China.

We study unextendible maximally entangled bases (UMEBs) in [Formula: see text] (d < d'). An operational method to construct UMEBs containing d(d' - 1) maximally entangled vectors is established, and two UMEBs in [Formula: see text] and [Formula: see text] are given as examples. Furthermore, a systematic way of constructing UMEBs containing d(d' - r) maximally entangled vectors in [Formula: see text] is presented for r = 1, 2, …, d - 1. Correspondingly, two UMEBs in [Formula: see text] are obtained.
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http://dx.doi.org/10.1038/s41598-018-21561-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816675PMC
February 2018

Polyphasic taxonomic characterisation of a novel strain as Pararhizobium haloflavum sp. nov., isolated from soil samples near a sewage treatment tank.

Antonie Van Leeuwenhoek 2018 Apr 13;111(4):485-491. Epub 2017 Nov 13.

College of Life Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.

A Gram-stain negative, aerobic, motile and ovoid- to rod-shaped bacteria strain, designated XC0140, was isolated from soil samples near the sewage treatment tank of a chemical factory in Zhejiang Province, China, and subjected to polyphasic taxonomic investigation. Strain XC0140 grew at 10-37 °C and pH 6.0-9.0 (optimum, 35 °C and pH 7.5) and with 0-17% (w/v) NaCl (optimum, 1%). According to phylogenetic analysis based on 16S rRNA gene sequences, strain XC0140 was assigned to the genus Pararhizobium with high 16S rRNA gene sequence similarity of 95.97% to "Pararhizobium helanshanense CCNWQTX14, followed by Pararhizobium sphaerophysae CCNWGS0238 (95.95%). Chemotaxonomic analysis showed that strain XC0140 contains ubiquinone-10 as the predominant respiratory quinone and possessed summed feature 8 (comprising C ω7c and/or ω6c), 11-methyl C ω7c, C and C as predominant forms of fatty acids. The polar lipids of strain XC0140 consisted of seven phospholipids (PL), two aminolipids (AL), one glycolipid (GL) and three unidentified lipids (L1, L2 and L3). The DNA G+C content was 62.7 mol%. Based on the polyphasic taxonomic characterization, strain XC0140 is considered to represent a novel species of the genus Pararhizobium, for which the name Pararhizobium haloflavum sp. nov. is proposed. (type strain XC0140 = MCCC 1K03228 = KCTC 52582).
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http://dx.doi.org/10.1007/s10482-017-0969-5DOI Listing
April 2018

miRNA‑148a inhibits cell growth of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways.

Oncol Rep 2017 Nov 7;38(5):3085-3093. Epub 2017 Sep 7.

Department of General Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

The function of miRNA‑148a in lymphatic metastases of papillary thyroid cancer and its mechanism were tested. In this investigation, miRNA‑148a expression of lymphatic metastases of papillary thyroid cancer patients was inhibited, compared with normal group. We found that miRNA‑148a overexpression was effectively reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer in vitro. Overexpression of miRNA‑148a significantly induced Bax protein expression and caspase‑3/9 levels, and suppressed phosphorylation STAT3 (p‑STAT3), PI3K and p‑Akt protein expression of papillary thyroid cancer in vitro. Next, si‑STAT3, could inhibit p‑STAT3 protein expression, reducing cell-cell proliferation and metastases, and inducing apoptosis of papillary thyroid cancer following miRNA‑148a overexpression. Then, the PI3K inhibitor was able to inhibit PI3K and p‑Akt protein expression, reduced cell cell proliferation and metastases, and induced apoptosis of papillary thyroid cancer following miRNA‑148a overexpression. Taken together, our results suggest that miRNA‑148a inhibits lymphatic metastases of papillary thyroid cancer through STAT3 and PI3K/AKT signaling pathways.
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http://dx.doi.org/10.3892/or.2017.5947DOI Listing
November 2017

Direct and Selective Synthesis of Hydrogen Peroxide over Palladium-Tellurium Catalysts at Ambient Pressure.

ChemSusChem 2017 09 17;10(17):3342-3346. Epub 2017 Aug 17.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China.

Highly selective hydrogen peroxide (H O ) synthesis directly from H and O is a strongly desired reaction for green processes. Herein a highly efficient palladium-tellurium (Pd-Te/TiO ) catalyst with a selectivity of nearly 100 % toward H O under mild conditions (283 K, 0.1 MPa, and a semi-batch continuous flow reactor) is reported. The size of Pd particles was remarkably reduced from 2.1 nm to 1.4 nm with the addition of Te. The Te-modified Pd surface could significantly weaken the dissociative activation of O , leading to the non-dissociative hydrogenation of O . Density functional theory calculations illuminated the critical role of Te in the selective hydrogenation of O , in that the active sites composed of Pd and Te could significantly restrain side reactions. This work has made significant progress on the development of high-selectivity catalysts for the direct synthesis of H O at ambient pressure.
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http://dx.doi.org/10.1002/cssc.201701238DOI Listing
September 2017

No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice.

Neural Regen Res 2016 Aug;11(8):1339-46

Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardiocerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, Guangdong Province, China.

Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.
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http://dx.doi.org/10.4103/1673-5374.189201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020835PMC
August 2016

Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK.

Neurochem Res 2016 Sep 9;41(9):2267-77. Epub 2016 May 9.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.

Oxidative stress mediates the pathogenesis of neurodegenerative disorders. Gartanin, a natural xanthone of mangosteen, possesses multipharmacological activities. Herein, the neuroprotection capacity of gartanin against glutamate-induced damage in HT22 cells and its possible mechanism(s) were investigated for the first time. Glutamate resulted in cell death in a dose-dependent manner and supplementation of 1-10 µM gartanin prevented the detrimental effects of glutamate on cell survival. Additional investigations on the underlying mechanisms suggested that gartanin could effectively reduce glutamate-induced intracellular ROS generation and mitochondrial depolarization. We further found that gartanin induced HO-1 expression independent of nuclear factor erythroid-derived 2-like 2 (Nrf2). Subsequent studies revealed that the inhibitory effects of gartanin on glutamate-induced apoptosis were partially blocked by small interfering RNA-mediated knockdown of HO-1. Finally, the protein expression of phosphorylation of AMP-activated protein kinase (AMPK) and its downstream signal molecules, Sirtuin activator (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), increased after gartanin treatment. Taken together, these findings suggest gartanin is a potential neuroprotective agent against glutamate-induced oxidative injury partially through increasing Nrf-2-independed HO-1 and AMPK/SIRT1/PGC-1α signaling pathways.
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http://dx.doi.org/10.1007/s11064-016-1941-xDOI Listing
September 2016

Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.

Neurochem Res 2016 Jul 2;41(7):1806-17. Epub 2016 Apr 2.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.

Natural xanthones have diversity pharmacological activities. Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced β-amyloid (Aβ) aggregation and also β-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators. Among these compounds, α-Mangostin, Gartanin, Garcinone C and γ-Mangostin showed better antioxidant properties to scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell death partly by up-regulating HO-1 protein level and then scavenging reactive oxygen species. Moreover, Gartanin, Garcinone C and γ-Mangostin could be able to penetrate the blood-brain barrier (BBB) in vitro. These findings suggest that the natural xanthones have multifunctional activities against Alzheimer's disease (AD) and could be promising compounds for the therapy of AD.
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http://dx.doi.org/10.1007/s11064-016-1896-yDOI Listing
July 2016

Degradation of trichloroethylene by hydrodechlorination using formic acid as hydrogen source over supported Pd catalysts.

J Hazard Mater 2016 Mar 1;305:178-189. Epub 2015 Dec 1.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology (ECUST), Shanghai 200237, China. Electronic address:

An advanced method for the degradation of trichloroethylene (TCE) over Pd/MCM-41 catalysts through a hydrogen-transfer was investigated. Formic acid (FA) was used instead of gaseous H2 as the hydrogen resource. As a model H-carrier compound, FA has proven to yield less by-products and second-hand pollution during the reaction. Several factors have been studied, including: the property of catalyst supports, Pd loading and size, temperature, initial concentrations of FA and TCE (potential impact on the reaction rates of TCE degradation), and FA decomposition. The intrinsic kinetics for TCE degradation were measured, while the apparent activation energies and the reaction orders with respect to TCE and FA were calculated through power law models. On the basis of kinetics, we assumed a plausible reaction pathway for TCE degradation in which the catalytic degradation of TCE is most likely the rate-determining step for this reaction.
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http://dx.doi.org/10.1016/j.jhazmat.2015.11.025DOI Listing
March 2016

Dimeric bis (heptyl)-Cognitin Blocks Alzheimer's β-Amyloid Neurotoxicity Via the Inhibition of Aβ Fibrils Formation and Disaggregation of Preformed Fibrils.

CNS Neurosci Ther 2015 Dec 28;21(12):953-61. Epub 2015 Oct 28.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.

Aims: Fibrillar aggregates of β-amyloid protein (Aβ) are the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit Aβ fibrils formation, disaggregate preformed Aβ fibrils as well as reduce their associated neurotoxicity might have therapeutic values for treating AD. In this study, the inhibitory effects of bis (heptyl)-cognitin (B7C), a multifunctional dimer derived from tacrine, on aggregation and neurotoxicity of Aβ1-40 were evaluated both in vitro and in vivo.

Methods: Thioflavin T fluorescence assay was carried out to evaluate Aβ aggregation, MTT and Hoechst-staining assays were performed to investigate Aβ-associated neurotoxicity. Fluorescent probe DCFH-DA was used to estimate the accumulation of intracellular reactive oxygen stress (ROS). Morris water maze was applied to determine learning and memory deficits induced by intracerebroventricular infusion of Aβ in rats.

Results: B7C (0.1-10 μM), but not tacrine, effectively inhibited Aβ fibrils formation and disaggregated preformed Aβ fibrils following co-incubation of B7C and Aβ monomers or preformed fibrils, respectively. In addition, B7C markedly reduced Aβ fibrils-associated neurotoxicity in SH-SY5Y cell line, as evidenced by the increase in cell survival, the decrease in Hoechst-stained nuclei and in intracellular ROS. Most encouragingly, B7C (0.1 and 0.2 mg/kg), 10 times more potently than tacrine (1 and 2 mg/kg), inhibited memory impairments after intracerebroventricular infusion of Aβ in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with upregulation of choline acetyltransferase activity and downregulation of acetylcholinesterase activity.

Conclusion: These findings provide not only novel molecular insight into the potential application of B7C in treating AD, but also an effective approach for screening anti-AD agents.
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http://dx.doi.org/10.1111/cns.12472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493105PMC
December 2015

A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine.

J Mol Neurosci 2015 Aug 17;56(4):977-987. Epub 2015 May 17.

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Huangpu Road, Guangzhou, 510632, China.

Neurodegenerative disorders are one of the leading causes of death among the elderly. Therapeutic approaches with a single target have proven unsuccessful in treating these diseases. Structural combination of multi-functional compounds may lead to a molecule with multiple properties. In this study, we designed and synthesized T-006, a novel analog derived from two multi-functional neuroprotective chemicals, tetramethylpyrazine and J147. The methoxyphenyl group of J147 was replaced by tetramethylpyrazine. Bioactivity evaluation showed that T-006 at very low concentrations had multi-functional neuroprotective effects including rescuing iodoacetic acid-induced neuronal loss, preventing oxidative stress-induced neurotoxicity and reducing glutamate-induced excitotoxicity in vitro. Most importantly, T-006 significantly ameliorated memory impairments in APP/PS1 transgenic mice. These multiple functions of a single molecule suggest that T-006 is a promising novel neuroprotective agent for treating various neurodegenerative disorders, including and in particular Alzheimer's disease.
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http://dx.doi.org/10.1007/s12031-015-0566-xDOI Listing
August 2015

Robust Neuritogenesis-Promoting Activity by Bis(heptyl)-Cognitin Through the Activation of alpha7-Nicotinic Acetylcholine Receptor/ERK Pathway.

CNS Neurosci Ther 2015 Jun 28;21(6):520-9. Epub 2015 Apr 28.

Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.

Aims: Neurodegenerative disorders are caused by progressive neuronal loss in the brain, and hence, compounds that could promote neuritogenesis may have therapeutic values. In this study, the effects of bis(heptyl)-cognitin (B7C), a multifunctional dimer, on neurite outgrowth were investigated in both PC12 cells and primary cortical neurons.

Methods: Immunocytochemical staining was used to evaluate the proneuritogenesis effects, and Western blot and short hairpin RNA assays were applied to explore the underlying mechanisms.

Results: B7C (0.1-0.5 μM) induced robust neurite outgrowth in PC12 cells, as evidenced by the neurite-bearing morphology and upregulation of growth-associated protein-43 expression. In addition, B7C markedly promoted neurite outgrowth in primary cortical neurons as shown by the increase in the length of β-III-tubulin-positive neurites. Furthermore, B7C rapidly increased ERK phosphorylation. Specific inhibitors of alpha7-nicotinic acetylcholine receptor (α7-nAChR) and MEK, but not those of p38 or JNK, blocked the neurite outgrowth as well as ERK phosphorylation induced by B7C. Most importantly, genetic depletion of α7-nAChR significantly abolished B7C-induced neurite outgrowth in PC12 cells.

Conclusion: B7C promoted neurite outgrowth through the activation of α7-nAChR/ERK pathway, which offers novel insight into the potential application of B7C in the treatment of neurodegenerative disorders.
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http://dx.doi.org/10.1111/cns.12401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495446PMC
June 2015

Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity.

Sci Rep 2015 Jan 23;5:7992. Epub 2015 Jan 23.

1] Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China [2] Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.

Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 ± 0.3 μM, which was smaller than that of (-)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aβ42 monomers and its mature fibrils into unstructured Aβ aggregates with some β-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aβ42 fibrillogenesis by directly binding to Aβ42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.
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http://dx.doi.org/10.1038/srep07992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303869PMC
January 2015

Stimulus-specific adaptation at the synapse level in vitro.

PLoS One 2014 8;9(12):e114537. Epub 2014 Dec 8.

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China.

Stimulus-specific adaptation (SSA) is observed in many brain regions in humans and animals. SSA of cortical neurons has been proposed to accumulate through relays in ascending pathways. Here, we examined SSA at the synapse level using whole-cell patch-clamp recordings of primary cultured cortical neurons of the rat. First, we found that cultured neurons had high firing capability with 100-Hz current injection. However, neuron firing started to adapt to repeated electrically activated synaptic inputs at 10 Hz. Next, to activate different dendritic inputs, electrical stimulations were spatially separated. Cultured neurons showed similar SSA properties in the oddball stimulation paradigm compared to those reported in vivo. Single neurons responded preferentially to a deviant stimulus over repeated, standard stimuli considering both synapse-driven spikes and excitatory postsynaptic currents (EPSCs). Compared with two closely placed stimulating electrodes that activated highly overlapping dendritic fields, two separately placed electrodes that activated less overlapping dendritic fields elicited greater SSA. Finally, we used glutamate puffing to directly activate postsynaptic glutamate receptors. Neurons showed SSA to two separately placed puffs repeated at 10 Hz. Compared with EPSCs, GABAa receptor-mediated inhibitory postsynaptic currents showed weaker SSA. Heterogeneity of the synaptic inputs was critical for producing SSA, with glutamate receptor desensitization participating in the process. Our findings suggest that postsynaptic fatigue contributes largely to SSA at low frequencies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114537PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259350PMC
January 2016

Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

CNS Neurosci Ther 2015 Jan 14;21(1):61-70. Epub 2014 Oct 14.

School of Chinese Medicine, University of Hong Kong, Hong Kong, China.

Aim: Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process.

Methods: We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit.

Results: Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; (2) ERK1/2, PI3K/Akt, and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner.

Conclusion: Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases.
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http://dx.doi.org/10.1111/cns.12334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495423PMC
January 2015

A novel tetramethylpyrazine bis-nitrone (TN-2) protects against 6-hydroxyldopamine-induced neurotoxicity via modulation of the NF-κB and the PKCα/PI3-K/Akt pathways.

Neurochem Int 2014 Dec 10;78:76-85. Epub 2014 Sep 10.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenue Padre Tomás Pereira S.J., Macao, China. Electronic address:

Introduction: The natural product tetramethylpyrazine (TMP) has a variety of biologic activities, including neuroprotection. Nitrones are powerful free radical scavengers. We have designed and synthesized a TMP derivative, TN-2, which is armed with two nitrone moieties.

Aims: In this study, we investigated the neuroprotective effect of TN-2 against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in zebrafish.

Methods: PC12 cells, zebrafish and rats were exposed to 6-OHDA challenge. MTT assay, LDH release, Hoechst staining, DAF-FM staining, luciferase reporter construct transfection, and western blotting were applied to detect cell viability, apoptosis, intracellular nitric oxide (NO), NF-κB transcriptional activity and proteins expression. In zebrafish, whole-mount staining and real-time PCR were performed to quantify dopaminergic neurons and mRNA expression. Hematoxylin and eosin staining and immunohistochemistry for glial fibrillary acidic protein were used to detect the astrocyte activation in the unilateral 6-OHDA rat model.

Results: TN-2 but not TMP exhibited potent neuroprotective effect against 6-OHDA-induced apoptosis in PC12 cells. Moreover, TN-2 prevented dopaminergic neuron loss and suppressed mRNA expression of pro-inflammatory genes, including IL-1β, TNF-α and COX-2, in 6-OHDA-treated zebrafish. TN-2 remarkably attenuated microglial/astrocyte activation in the unilateral 6-OHDA rat model. The mechanistic study demonstrated that TN-2 inhibited over-production of intracellular NO and protein expression of inducible nitric oxide synthase through down-regulating NF-κB activity. Additionally, the PKCα/PI3-K/Akt pathway was also involved in the neuroprotection of TN-2.

Conclusion: These results suggest that TN-2 protected against 6-OHDA-induced neurotoxicity via modulating the NF-κB-medicated neuroinflammation and PKCα/PI3-K/Akt pathways.
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http://dx.doi.org/10.1016/j.neuint.2014.09.001DOI Listing
December 2014

Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: involvement of Nrf2/HO-1 pathway.

CNS Neurosci Ther 2014 Sep 12;20(9):840-50. Epub 2014 Jun 12.

Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.

Aims: Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death.

Methods And Results: T3CA protected HT22 cells against high-concentration-glutamate-induced cell death in time- and concentration-dependent manners and potently attenuated glutamate-induced intracellular reactive oxygen species (ROS) production as well as mitochondrial membrane-potential (ΔΨ) disruption. Besides, T3CA significantly induced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased its transcriptional activity, which were demonstrated by Western blotting, immunofluorescence, and antioxidant response element (ARE)-luciferase reporter gene assay. Further studies showed that T3CA potently up-regulated heme oxygenase-1 (HO-1), an endogenous antioxidative enzyme and a downstream effector of Nrf2, at both mRNA and protein levels. The neuroprotective effects of T3CA were partially reversed by brusatol, which reduced protein level of Nrf2, or by inhibiting HO-1 with siRNA or ZnPP-IX, a specific inhibitor of HO-1.

Conclusions: Taken together, these results clearly demonstrate that T3CA protects neurons against OS-induced cell death partially through Nrf2/ARE/HO-1 signaling pathway, which further supports that T3CA might be a promising novel therapeutic agent for OS-associated diseases.
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http://dx.doi.org/10.1111/cns.12286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493203PMC
September 2014

Sunitinib produces neuroprotective effect via inhibiting nitric oxide overproduction.

CNS Neurosci Ther 2014 Mar 7;20(3):244-52. Epub 2014 Jan 7.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR, China; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, China.

Background: Sunitinib is an inhibitor of the multiple receptor tyrosine kinases (RTKs) for cancer therapy. Some sunitinib analogues could prevent neuronal death induced by various neurotoxins. However, the neuroprotective effects of sunitinib have not been reported.

Methods: Cerebellar granule neurons (CGNs) and SH-SY5Y cells were exposed to low-potassium and MPP(+) challenges, respectively. MTT assay, FDA/PI staining, Hoechst staining, DAF-FM, colorimetric nitric oxide synthase (NOS) activity assay, and Western blotting were applied to detect cell viability, NO production, NOS activity, and neuronal NOS (nNOS) expression. Short hairpin RNA was used to decrease nNOS expression. In vitro NOS enzyme activity assay was used to determine the direct inhibition of nNOS by sunitinib.

Results: Sunitinib prevented low-potassium-induced neuronal apoptosis in CGNs and MPP(+) -induced neuronal death in SH-SY5Y cells. However, PTK787, another RTK inhibitor, failed to decrease neurotoxicity in the same models. Sunitinib reversed the increase in NO levels, NOS activity, and nNOS expression induced by low potassium or MPP(+) . Knockdown of nNOS expression partially abolished the neuroprotective effects of sunitinib. Moreover, sunitinib directly inhibited nNOS enzyme activity.

Conclusions: Sunitinib exerts its neuroprotective effects by inhibiting NO overproduction, possibly via the inhibition of nNOS activity and the decrease in nNOS expression.
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http://dx.doi.org/10.1111/cns.12203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493018PMC
March 2014

Iron oxychloride (FeOCl): an efficient Fenton-like catalyst for producing hydroxyl radicals in degradation of organic contaminants.

J Am Chem Soc 2013 Oct 16;135(43):16058-61. Epub 2013 Oct 16.

State Key Laboratory of Chemical Engineering, East China University of Science and Technology (ECUST) , Shanghai 200237, China.

An iron oxychloride (FeOCl) catalyst was developed for oxidative degradation of persistent organic compounds in aqueous solutions. Exceptionally high activity for the production of hydroxyl radical (OH·) by H2O2 decomposition was achieved, being 2-4 orders of magnitudes greater than that over other Fe-based heterogeneous catalysts. The relationship of catalyst structure and performance has been established by using multitechniques, such as XRD, HRTEM, and EPR. The unique structural configuration of iron atoms and the reducible electronic properties of FeOCl are responsible for the excellent activity. This study paves the way toward the rational design of relevant catalysts for applications, such as wastewater treatment, soil remediation, and other emerging environmental problems.
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http://dx.doi.org/10.1021/ja409130cDOI Listing
October 2013

Substantial neuroprotection against K+ deprivation-induced apoptosis in primary cerebellar granule neurons by novel dimer bis(propyl)-cognitin via the activation of VEGFR-2 signaling pathway.

CNS Neurosci Ther 2013 Oct 4;19(10):764-72. Epub 2013 Jul 4.

Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; The Hong Kong Polytechnic University, Shenzhen Research Institute, Shenzhen, China.

Background: Neuronal loss via apoptosis in CNS is the fundamental mechanism underlying various neurodegenerative diseases. Compounds with antiapoptotic property might have therapeutic effects for these diseases. In this study, bis(propyl)-cognitin (B3C), a novel dimer that possesses anti-AChE and anti-N-methyl-d-aspartate receptor activities, was investigated for its neuroprotective effect on K(+) deprivation-induced apoptosis in cerebellar granule neurons (CGNs).

Methods: Cerebellar granule neurons were switched to K(+) deprived medium with or without B3C. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay, fluorescein diacetate (FDA)/propidium iodide (PI) staining, Hoechst staining, and DNA laddering assays were applied to detect cytotoxicity and apoptosis. Additionally, the expression of p-VEGFR-2, p-Akt, p-glycogen synthase kinase 3β (GSK3β), and p-extracellular signal-regulated kinase (ERK) was examined in CGNs.

Results: Switching CGNs to K(+) deprived medium resulted in remarkable apoptosis, which could be substantially blocked by B3C treatment (IC50 , 0.37 μM). Moreover, a rapid decrease in p-Tyr1054-VEGFR-2 was observed after the switch. B3C significantly reversed the inhibition of p-Tyr1054-VEGFR-2 as well as Akt and ERK pathways. VEGFR-2 inhibitor PTK787/ZK222584, as well as PI3-K inhibitor LY294002 and MEK inhibitor PD98059, each abolished the neuroprotective effect of B3C.

Conclusions: Our results demonstrate that B3C blocks K(+) deprivation-induced apoptosis in CGNs through regulating VEGFR-2/Akt/GSK3β and VEGFR-2/ERK signaling pathways, providing a molecular insight into the therapeutic potential of B3C for the treatment of neurodegenerative diseases.
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http://dx.doi.org/10.1111/cns.12141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493391PMC
October 2013

New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics.

Evid Based Complement Alternat Med 2013 24;2013:627375. Epub 2013 Mar 24.

School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100102, China.

With tens of thousands of plant species on earth, we are endowed with an enormous wealth of medicinal remedies from Mother Nature. Natural products and their derivatives represent more than 50% of all the drugs in modern therapeutics. Because of the low success rate and huge capital investment need, the research and development of conventional drugs are very costly and difficult. Over the past few decades, researchers have focused on drug discovery from herbal medicines or botanical sources, an important group of complementary and alternative medicine (CAM) therapy. With a long history of herbal usage for the clinical management of a variety of diseases in indigenous cultures, the success rate of developing a new drug from herbal medicinal preparations should, in theory, be higher than that from chemical synthesis. While the endeavor for drug discovery from herbal medicines is "experience driven," the search for a therapeutically useful synthetic drug, like "looking for a needle in a haystack," is a daunting task. In this paper, we first illustrated various approaches of drug discovery from herbal medicines. Typical examples of successful drug discovery from botanical sources were given. In addition, problems in drug discovery from herbal medicines were described and possible solutions were proposed. The prospect of drug discovery from herbal medicines in the postgenomic era was made with the provision of future directions in this area of drug development.
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http://dx.doi.org/10.1155/2013/627375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619623PMC
May 2013

Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

Brain Res 2012 Aug 29;1470:59-68. Epub 2012 Jun 29.

Shanghai Jiao Tong University, Shanghai, China.

Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 μmol/kg), B7C (0.4-0.6 μmol/kg) or tacrine (8-12 μmol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations.
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http://dx.doi.org/10.1016/j.brainres.2012.06.015DOI Listing
August 2012

New perspectives on chinese herbal medicine (zhong-yao) research and development.

Evid Based Complement Alternat Med 2011 10;2011:403709. Epub 2011 Mar 10.

Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, China.

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.
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http://dx.doi.org/10.1093/ecam/neq056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135515PMC
November 2011

Tacrine and bis(7)-tacrine attenuate cycloheximide-induced amnesia in mice, with attention to acute toxicity.

Basic Clin Pharmacol Toxicol 2011 Oct 31;109(4):261-5. Epub 2011 May 31.

Department of Pharmacology, Beijing University of Chinese Medicine, Beijing, China.

Effects of tacrine and bis(7)-tacrine (0.25-20 μmol/kg, s.c.) on cognitive behaviour in cycloheximide (CYH)-treated mice were investigated. Cognitive behaviour was assessed by open-field test and step-through task with a 24-hr retention interval. Drugs or vehicle was given 30 min. prior to the first session. Although CYH treatment (110 mg/kg, i.p.) alone did not affect the locomotor activity of mice, CYH treatment in combination with tacrine (20 μmol/kg) decreased the locomotor activity by 37% in the acquisition session, when compared with mice treated with CYH alone. Bis-(7) tacrine cotreatment did not produce any detectable effect on locomotor activity. During the retention trial, tacrine (5 μmol/kg) or bis(7)-tacrine (1 μmol/kg) enhanced the retention latency (by 3.8- or 1.4-fold, respectively) in CYH-treated mice. In both training and retention trials, CYH treatment increased the number of footshocks (by 50% and 11.3-fold, respectively). However, during the retention (but not training) trial, tacrine (5 μmol/kg) or bis(7)-tacrine (1 μmol/kg) decreased the footshocks (by 8.6-fold or 39%, respectively) in CYH-treated mice. Combined treatment with CYH and bis(7)-tacrine (but not tacrine) resulted in an increased mortality rate in mice. The results indicated that tacrine and bis(7)-tacrine improved the amnesia caused by CYH treatment. However, the combined treatment with bis(7)-tacrine and CYH administration caused acute toxicity.
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http://dx.doi.org/10.1111/j.1742-7843.2011.00715.xDOI Listing
October 2011