1.Discovery of potential nicotinic acid receptor agonists from Chinese herbal medicines based on molecular simulation.
Lu-Di JIANG ; Yu-Su HE ; Yan-Ling ZHANG
China Journal of Chinese Materia Medica 2014;39(23):4653-4657
Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical
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Drugs, Chinese Herbal
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chemistry
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Humans
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Models, Molecular
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Molecular Structure
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Nicotinic Acids
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chemistry
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Nicotinic Agonists
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chemistry
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Protein Binding
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Receptors, G-Protein-Coupled
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agonists
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chemistry
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Receptors, Nicotinic
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chemistry
2.Method of traditional Chinese medicine formula design based on 3D-database pharmacophore search and patent retrieval.
Yu-su HE ; Zhi-yi SUN ; Yan-ling ZHANG
China Journal of Chinese Materia Medica 2014;39(22):4411-4417
By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents
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chemistry
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pharmacology
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Databases, Factual
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Medicine, Chinese Traditional
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methods
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Mineralocorticoid Receptor Antagonists
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chemistry
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pharmacology
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Models, Molecular
3.Study on structure-activity relationship of flavonoids' multidrug resistance-associated protein inhibitory activity.
Lian-Sheng QIAO ; Yu-Su HE ; Yan-Ling ZHANG
China Journal of Chinese Materia Medica 2014;39(5):885-890
To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal
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chemistry
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pharmacology
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Flavonoids
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chemistry
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pharmacology
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Humans
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Models, Molecular
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Multidrug Resistance-Associated Proteins
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antagonists & inhibitors
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chemistry
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Quantitative Structure-Activity Relationship
4.Study on self-similarity of property combination mode of traditional Chinese medicines.
Jing SUN ; Bai-Xia ZHANG ; Su-Rong YAN ; Yan-Ling ZHANG ; Yun WANG ; Yan-Jiang QIAO
China Journal of Chinese Materia Medica 2014;39(13):2378-2381
The combination of medicinal properties refers to expression forms of elements with active properties combined according to a specific sequence. The mode of medicinal property combination refers to the compatible relationship multiple medicinal property combinations. In this paper, based on the mode, safflower, Taohong Siwu decoction, Xuefu Zhuyu decoction and Buyang Huanwu decoction were taken for example to study the characteristics of the compatibility among single herb, herbal pairs and prescriptions. The authors discovered the similarities and differences among them, interpreted the self-similarity in medicinal property combinations of traditional Chinese medicines, and analyzed the compatible relationship among multiple medicinal property combinations, so as to bring forth new ideas in discovering the correlation between the compatibility study mode of traditional Chinese medicines based medicinal property combinations and the efficient compatibility of medicinal property combination.
Drug Combinations
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Drug Prescriptions
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Drug Therapy
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Humans
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Medicine, Chinese Traditional
5.Inhibition of polylysine-EDTA on rabbit lens epithelial cell growth in vitro
Hai-yan, ZHANG ; Ying-qi, LI ; Su-jiong, ZHANG ; Yuan-ling, XIA ; Yan-ni, YU
Chinese Journal of Experimental Ophthalmology 2011;29(9):831-833
BackgroundPosterior capsule opacification(PCO) is the main cause inducing low vision after extacapsular cataract extraction. Our previous study determined that polylysine-ethylene diamine tetraacetic acid (EDTA) (PLE) can suppress the incidence of PCO. ObjectiveThe goal of this experiment was to investigate the inhibition of polylysine-EDTA on rabbit lens epithelial cells (LECs)proliferation in vitro and the effective concentrations of polylysine-EDTA. MethodsThe anterior capsular membranes from 10 3-month-old clean New Zealand white rabbits were digested and then cultured to obtain the LECs. The second and third generation of LECs were inoculated on the 96-hole culture plate with the cell density of the 1 × 105/ml. 12.5,25.0,50. 0,100. 0 μmol/Lof PLE were added into the culture medium for 48 hours respectively,and the DMSO medium was used at the same way as the control group. The proliferation of the LECs was then detected by MTT method and the inhibitory rate of PLE on LECs growth was calculated. ResultsLECs grew at a near normal state in ≤25.0 μmol/L PLE groups,however,cultured LECs were out of shape and the numbers decreased with the weakened adhesion ability in ≥50.0 μ mol/L PLE groups. The A490 values of LECs were 0. 278±0. 013,0. 266±0. 028,0. 260±0. 022 and 0. 247±0. 012 in 12. 5,25.0,50. 0, 100. 0 μmol/L polylysine-EDTA groups respectively and were lower than 0. 311 ±0. 038 of DMSO control group( P=0. 035,0. 011,0. 009,0.013 ). The inhibitory rates of 12. 5,25.0,50. 0, 100.0 μmoL/L PLE on LECs proliferation were 10.61% , 14.47% , 16.40% and 20. 58% respectively. ConclusionsPolylysine-EDTA can inhibit the growth and proliferation of LECs in vitro at a dose-dependent manner.
6.Significance of Serum Interleukin-6 in Attack or Stable Stage of Asthmatic Children
zhi-hong, WEN ; mei, HONG ; yan-ling, TAO ; qiong-yan, HU ; li-hua, SU
Journal of Applied Clinical Pediatrics 1994;0(04):-
Objective To explore the role and clinical significance of interleukin-6(IL-6) in children with bronchial asthma.Methods Sera were collected from 29 cases with asthmatic attacks,32 asthmatic children who in stable conditions,and 20 health children.Serum IL-6 concentrations were measured by radioimmunoassay(RIA).Results 1.Asthmatic children appeared significantly higher levels of serum IL-6 during asthmatic attacks as compared to those in stable conditions and healthy ones respectively(P3 years old had significantly higher serum IL6 concentrations than ≤3 years old children in remission.Conclusion IL-6 may participate pathogenesis of asthma,and it may play different biological roles during asthmatic attacksas or stable conditions.
7.The relationship between insulin resistance and erythrocyte insulin receptors in patients with gout as- sociated with macroalbruminuria
Jian YU ; Feng LIN ; Ke SU ; Yan LONG ; Su-Xian ZHOU ; Yan ZHOU ; Yong-Ling HU ; Ying PENG ;
Chinese Journal of Rheumatology 2003;0(07):-
Objective To investigate the relationship between insulin resistance and erythrocyte in- sulin receptors in patients with gout associated with macroalbruminuria(MAU).Methods FBG,PBG,FINS, P2hINS,CH,TG,HDL,LDL-c,UA and erythrocyte insulin receptors were determined in 44 patients with MAU,62 patients with normal MAU(NMAU).Results In MAU,the levels of FINS,TG,LDL-c and HOMA-IR were(16?4)mU/L,(2.5?0.6)retool/L,(3.2?0.5)mmol/L and 3.6~1.2 respectively.While they were(13?3) mU/L,(2.3?0.8)mmol/L,(3.0?0.5)mmol/L and 3.0~0.4 in NMAU group.The levels of FINS,TG,LDL-c and HOMA-IR were significantly higher in the MAU patients than those in NMAU patients(P
8.Probing into Second Pathological Factors of Sjögren's Syndrome.
Cheng-yin LI ; Ting-ting YAN ; Su-ling WU ; Wang YUE
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(6):752-754
Sjögren's syndrome is a chronic autoimmune disease with unclear etiology. From the point of etiology, Chinese medicine (CM) theory holds that pathological products like dry toxin, blood stasis are produced in the pathological process. They are both pathologic results and pathogenic factors for its further development. So pathological products are also named as second pathogenic factors. In this article, the concept of second pathogenic factors was sorted and defined. Main second pathogenic factors of Sjögren's syndrome were pinpointed, and their modern medical bases were analyzed. Authors came to a conclusion that clearing away second pathogenic factors is a key point in treating Sjögren's syndrome.
Humans
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Sjogren's Syndrome
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pathology
9.Lethal effect of VEGFR_2 shRNA on HL60 cells in vitro using lentiviral vector
Haixia GUO ; Wenyi LI ; Ling XU ; Haobin SU ; Yang LI ; Yan XIA ; Liyang LIANG
Chinese Journal of Pathophysiology 1989;0(06):-
AIM: To look for harmfulless anti-leukemia drug with selective high performance, lethal effect of small hairpin RNA (shRNA) on VEGFR2 gene expression of tumor cell line HL60 in vitro.METHODS: The most effective VEGFR2 siRNA was designed and screened. The shRNA oligo was designed and pU6/VEGFR2 entry clone was constructed. HL60 was transfected transiently and vascular endothelial growth factor receptor 2(VEGFR2) expression was tested with MTT assay, RT-PCR and Western blotting. The expression clone was constructed and cotransfected with ViraPowerTM Packaging Mix into 293FTTM cells to produce Lentiviral vectors harboring Lenti6/shVEGFR2. The virion supernatant was added into HL60 cells and VEGFR2 gene inhibitory effect was determined. RESULTS: The inhibitory rates of VEGFR2 siRNA c were high. VEGFR2 expression in HL60 was inhibited by using pU6/VEGFR2 entry clone constructed with shRNA and pENTRTM/U6. For HL60 cells, the inhibitory rate was 84.9%. The expression of VEGFR2 mRNA and protein decreased significantly. 48 hours after transfection of pU6/shVEGFR2 entry clone and transduction of Lenti6/shVEGFR2 expression clone, the cell inhibitory rates were similar. Cell growth inhibitory rate of entry clone descended rapidly after this time point, the expression clone changed slowly, reaching the peak at 96 hours, dropped slightly, having no significance deviation. CONCLUSION: in vitro, VEGFR2 shRNA using lentiviral vector blocks VEGF/VEGFR2 self-secretion in HL60 cells, which inhibits leukemia development.
10.Analysis of an acute respiratory infection outbreak caused by adenovirus
Han ZHAO ; Qin LI ; Jiang LONG ; Yu XIA ; Kun SU ; Hua LING ; Yan FENG
Chongqing Medicine 2015;(4):506-508
Objective To analyze the investigation results of an acute respiratory infection outbreak caused by adenovirus and provide scientific information for the prevention and control of congener public health emergencies .Methods A case‐control study was performed with grades and gender as matching factor ,all cases and selected controls were investigated with the same question‐naire .Results A totul of 47 cases were diagnosed in the outbreak ,no death ,the attack rate was 8 .88% ;the main clinical symptom was fever and 27 .7% of the cases became pneumonia .The case‐control study analysis demonstrated that with close contact to cases or not(χ2 =7 .96 ,P<0 .05) ,contact time (χ2 =7 .95 ,P<0 .05) ,hand washing habits (χ2 =25 .92 ,P<0 .05) and with or without the habit of cleaning snivel by hand directly (χ2 =22 .78 ,P<0 .05) were statistically different between cases and controls .Conclu‐sion long‐time contact to cases maybe the main risk factor for the adenovirus infection ,especially the contact manner were sharing the same desk or playing together .A good health habit of washing hands often and no cleaning snivel by hand directly were impor‐tant protective factors .Thus ,strengthening the training of health habit and awareness is the important preventive measure for re‐spiratory infectious diseases .