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Gao L.,Peking Union Medical College | Zhao G.,Peking Union Medical College | Fang J.-S.,Peking Union Medical College | Yuan T.-Y.,Peking Union Medical College | And 4 more authors.
FEBS Journal | Year: 2014

Based on public gene expression data, we propose a computational approach to optimize gene expression signatures for the use with Connectivity Map (CMap) to reposition drugs or discover lead compounds for Parkinson's disease. This approach integrates genetic information from the Gene Expression Omnibus (GEO) database, the Parkinson's disease gene expression database (ParkDB), the Online Mendelian Inheritance in Man (OMIM) database and the Comparative Toxicogenomics Database (CTD), with the aim of identifying a set of interesting genes for use in computational drug screening via CMap. The results showed that CMap, using the top 20 differentially expressed genes identified by our approach as a gene expression signature, outperformed the same method using all differentially expressed genes (n = 535) as a signature. Utilizing this approach, the candidate compound alvespimycin (17-DMAG) was selected for experimental evaluation in a model of rotenone-induced toxicity in human SH-SY5Y neuroblastoma cells and isolated rat brain mitochondria. The results showed that 17-DMAG significantly attenuated rotenone-induced toxicity, as reflected by the increase of cell viability, the reduction of intracellular reactive oxygen species generation and a reduction in mitochondrial respiratory dysfunction. In conclusion, this computational method provides an effective systematic approach for drug repositioning or lead compound discovery for Parkinson's disease, and the discovery of the neuroprotective effects of 17-DMAG supports the practicability of this method. © 2013 FEBS.

Gao L.,Peking Union Medical College | Gao L.,Modern Medicine | Li C.,Peking Union Medical College | Yang R.-Y.,Peking Union Medical College | And 8 more authors.
Pharmacology Biochemistry and Behavior | Year: 2015

Baicalein, a flavonoid from Scutellaria baicalensis Georgi, has been shown to possess neuroprotective properties. The purpose of this study was to explore the effects of baicalein on motor behavioral deficits and gene expression in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease (PD). The behavioral results showed that baicalein significantly improves the abnormal behaviors in MPTP-induced mice model of PD, as manifested by shortening the total time for climbing down the pole, prolonging the latent periods of rotarod, and increasing the vertical movements. Using cDNA microarray and subsequent bioinformatic analyses, it was found that baicalein significantly promotes the biological processes including neurogenesis, neuroblast proliferation, neurotrophin signaling pathway, walking and locomotor behaviors, and inhibits dopamine metabolic process through regulation of gene expressions. Based on analysis of gene co-expression networks, the results indicated that the regulation of genes such as LIMK1, SNCA and GLRA1 by baicalein might play central roles in the network. Our results provide experimental evidence for the potential use of baicalein in the treatment of PD, and revealed gene expression profiles, biological processes and pathways influenced by baicalein in MPTP-treated mice. © 2015 Elsevier Inc. All rights reserved.

Feng K.-P.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | Chen R.-D.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | Chen R.-D.,Key Laboratory of Biosynthesis of Natural Products of National Health and Family Planning Commission | Chen R.-D.,Peking Union Medical College | And 7 more authors.
Journal of Asian Natural Products Research | Year: 2016

Two new flavonoids (1 and 2), along with 14 known ones (3-16), were isolated from the cultured cells of Glycyrrhiza uralensis. Most of them were prenylated flavonoids. Their structures were elucidated on the basis of spectroscopic data analysis. All compounds showed non-cytotoxicity against five human tumor cell lines. The results suggest that plant cultured cells can yield the secondary metabolites that have not been found in parent plant. © 2015 Taylor & Francis.

Lu H.-N.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | Liu Y.-B.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | Qu J.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | Li Y.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | And 3 more authors.
Journal of Asian Natural Products Research | Year: 2015

Two new sesquiterpenes, oligandrin (1) and oligandric acid (2), together with three analogues, tashironin A (3), tashironin (4), and oplodiol (5), were isolated from the roots of Illicium oligandrum. The structures of new compounds were determined based on 1D and 2D NMR experiments and X-ray diffraction. Compound 1 represents a presumed biosynthetic precursor of seco-prezizaane sesquiterpenes which consists of a novel 6/6/5 tricarbocyclic skeleton. Compound 2 is the first example of chamipinene-type sesquiterpene possessing a 6/4/6 tricyclic system from the genus Illicium. Compounds 1–5 were evaluated in vitro for their activity against coxsackie virus B3 (CVB3), influenza virus A/Hanfang/359/95 (H3N2), and influenza virus A/FM/1/47 (H1N1). Compound 1 showed selective antiviral activity against CVB3 with IC50 value of 11.11 μM. © 2015 Taylor & Francis

Fang J.-S.,Peking Union Medical College | Liu A.-L.,Peking Union Medical College | Liu A.-L.,Beijing Key Laboratory of Drug Target and Screening Research | Liu A.-L.,State Key Laboratory of Bioactive Substance and Function of Natural Medicines | And 3 more authors.
Yaoxue Xuebao | Year: 2014

The emerging of network pharmacology and polypharmacology forces the scientists to recognize and explore new mechanisms of existing drugs. The drug target prediction can play a key significance on the elucidation of the molecular mechanism of drugs and drug reposition. In this paper, we systematically review the existing approaches to the prediction of biological targets of small molecule based on chemoinformatics, including ligand-based prediction, receptor-based prediction and data mining-based prediction. We also depict the strength of these methods as well as their applications, and put forward their developing direction.

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