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.Comparison of histomorphological changes between osteoarthritis and kaschin-beck disease with knee arthroscope
Ming LING ; Zhi YI ; Yanhai CHANG ; Jianfa LI ; Zhenqun LUO
Chinese Journal of Tissue Engineering Research 2005;9(30):268-269
BACKGROUND: The pathological changes of osteoarthritis are similar to that of kaschin-beck disease, but the cause of the latter is still unclear,damage is more serious. From the comparison of pathology changes between them, we hope to find out an effective therapeutic method with the assistance of arthroscope basing on the experiences in osteoarthritis.OBJECTIVE: To make comparison of the histomorphological changes between osteoarthritis and kaschin-beck disease with knee arthroscope,which give clues to the diagnosis and selection of operative technique for kaschin-bock disease under arthroscope.DESIGN: Case control study.SETTING: Department of Orthopaedics, Shaanxi People's Hospital.PARTICIPANTS: Thirty-five patients who needed arthroscope surgery due to severer knee osteoarthritis were randomly selected from Department of Orthopaedics, Shaanxi People's Hospital between April 1998 and September 2000; Meanwhile 31 patients with knee joint functional obstacle caused by kaschin-beck disease (epidemic disease area) were randomly selected from Luochuan Hospital of Shaanxi Province in November 2001.METHODS: Japanese made OLYMPUS series color television arthroscope and surgery system were used to carry out knee joint operations in all participants. During the operation, video recording, postoperative editing, photographs, comparison and analysis were conducted, in order to find out the pathological changes of the two groups in knee joint synovium, patella, femur, tibia and meniscus with the assistance of arthroscope.RESULTS: Totally 66 patients were enrolled in this study and all endamage in Kaschin-beck disease and osteoarthritis: Injuries were graded into grade 0, 1, 2 and 3, there were 0,3,5,23 cases and 0,3,16,16cases correspondingly in kaschin-beck disease group and osteoarthritis cartilage damage was presented by big piece of cartilage peeled off, part of them came off leading to bone exposure, the exposed bone surface is uneven; while cartilage damage in osteoarthritis was presented by the wear of cartilage, moreover cartilage island was found remained in the exposed bone with the surface covered with fiber strips and the exposed observed in 24 patients with Kaschin-beck disease, 5 cases with coarse stress point and 19 cases with burr-like damage, amongst which there were 9 cases displayed both medial and lateral meniscus damages; in osteoarthritis group there were 16 cases showed meniscus damages including edge wears in11 cases and breakage in 5 cases.CONCLUSION: Cartilage damage in knee articular was obviously severer in Kaschin-beck disease than in osteoarthritis, although kaschin-beck disease is no matter resulting in serious knee joint damage, but its pathology changes are different from osteoarthritis, we should pay more attention to the peculiarity of big piece of cartilage peeling off during operations.
4.The antagonism of cholecystokinin octapeptide-8 to the peroxynitrite oxidation on a diabetic cataractal rat model.
Li-na HAO ; Yi-qun LING ; Qi-yan MAO ; Yi-ling LING ; Shou-zhi HE
Chinese Medical Journal 2006;119(17):1451-1457
BACKGROUNDCataracts is considered be formed because of an abnormal glucose metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and antagonism of cholecystokinin octapeptide-8 (CCK-8) in diabetic cataractal rat lenses.
METHODSA diabetic cataractal animal model was established by peritoneal injection of streptozotocine (STZ). Thirty-six normal SD rats were taken as control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20, 40 and 60 days. Immunofluorescent staining and Western blot analysis were used for determining nitrotyrosine (NT, a marker for ONOO-). PT-PCR and gene array analysis were used for determining the expression of inducible nitric oxide synthetase mRNA (iNOS mRNA) in lens epithelium (LEC).
RESULTSSTZ group rats developed lens opacity by 20 days that reached a high level by 60 days after STZ injection. CCK-8 group rats delayed the cataract formation. CCK-8 group rats delayed the cataract formation. There was no distinct expression of NT and iNOS mRNA in control group. In STZ group, there were distinct expression of NT and upregulation of iNOS mRNA; however, CCK-8 group showed weak expression of NT and downregulation of iNOS mRNA.
CONCLUSIONSNT, which may be a new form of oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be related to direct antagonism of ONOO- as well as its inhibition of the expression of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO-.
Animals ; Blotting, Western ; Cataract ; etiology ; prevention & control ; Diabetes Mellitus, Experimental ; complications ; Fluorescent Antibody Technique ; Male ; Nitric Oxide Synthase Type II ; genetics ; Oxidation-Reduction ; Peroxynitrous Acid ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sincalide ; pharmacology ; Streptozocin ; Tyrosine ; analogs & derivatives ; genetics
5.Relevant factors on the degree of anterior uveitis in patients with ankylosing spondylitis
Guo-Xiang, SONG ; Jin-Xian, HUANG ; Ya-Ling, DENG ; Zhi-Hua, YIN ; Zhang-Yi, LIANG ; Zhi-Zhong, YE
International Eye Science 2014;(7):1310-1312
AlM: To investigate the association between the degree of anterioruveitis and related factors including inflammatory markers as well as sacroiliac joint imaging in patients with ankylosing spondylitis ( AS) .
METHODS: Anterior changes evaluated by slit lamp, erythrocyte sedimentation rate ( ESR ) , C - reactive protein ( CRP ) and magnetic resonance imaging of 55 cases with AS associateduveitis were retrospectively analyzed. A modified endotoxin-induced uveitis ( ElU ) clinical standard was used for uveitis grading. SPARCC sacroiliac scoring was used to evaluate bone edema of sacroiliac joint. The correlation between the degree of uveitis and sacroiliitis was assessed.
RESULTS: ln the 55 patients with AS, ElU grading scored 2-10, and SPARCC index scored 0-22. Further analysis showed that the severity of uveitis was significantly correlated with ESR (r=0. 869, P<0. 001) and CRP (r=0. 485, P<0. 001). The degree of anterior uveitis in AS patients was not correlated with inflammation of sacroiliac joint (r=0. 237, P=0. 081).
CONCLUSlON: Local autoimmunity of uveitis and sacroiliac joint inflammation with subsequent bone formation in AS might be mutually independent processes.
6.Association between coronary artery stenosis and peripheral artery function in normotensive and hypertensive patients with coronary artery disease.
Chinese Journal of Cardiology 2007;35(10):885-888
OBJECTIVETo observe the relationship between the parameters of artery elasticity and coronary artery stenosis in normotensive and hypertensive patients with coronary artery disease (CAD).
METHODSSystemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery compliance (BAC) and brachial artery resistance (BAR) were measured by Dynapulse 200M (Pulse Metric, Inc., USA) in 88 hypertensive and 41 normotensive patients with chest pain before coronary artery angiography.
RESULTS(1) The prevalence rate of severe coronary disease (> or = 2 coronary branches) was higher in hypertensives than in normotensives (64.7% vs. 27.1%, P < 0.05); (2) the peripheral artery buffering function was significantly lower in hypertensives than in normotensives [SVC: (0.85 +/- 0.10) ml/mm Hg (1 mm Hg = 0.133 kPa) vs. (1.17 +/- 0.11) ml/mm Hg; BAC: (0.047 +/- 0.011) ml/mm Hg vs. (0.063 +/- 0.010) ml/mm Hg, all P < 0.05]; (3) Lower arterial elasticity was associated with severe coronary artery stenosis.
CONCLUSIONThe non-invasive obtained artery elasticity is associated with the degree of coronary artery stenosis in hypertensive patients with CAD.
Aged ; Blood Pressure ; Coronary Angiography ; Coronary Artery Disease ; complications ; diagnostic imaging ; physiopathology ; Coronary Stenosis ; complications ; diagnostic imaging ; physiopathology ; Female ; Humans ; Hypertension ; complications ; diagnostic imaging ; physiopathology ; Male ; Middle Aged ; Prevalence ; Pulse
7.Pathologic observation of spleen dendritic cells in mouse multiple organ failure model.
Jiang-yang LU ; Zhi-hong LI ; Xiao-hong WANG ; Yi YANG ; Ling LI
Chinese Journal of Pathology 2005;34(7):427-428
Animals
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Antigens, CD
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metabolism
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Apoptosis
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B7-2 Antigen
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metabolism
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CD4-CD8 Ratio
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Dendritic Cells
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metabolism
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pathology
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Disease Models, Animal
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Lectins, C-Type
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metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Minor Histocompatibility Antigens
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Multiple Organ Failure
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metabolism
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pathology
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Receptors, Cell Surface
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metabolism
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Spleen
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metabolism
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pathology
8.Study on lipid-lowering traditional Chinese medicines based on pharmacophore technology and patent retrieval.
Xiao-qian HUO ; Yu-su HE ; Lian-sheng QIAO ; Zhi-yi SUN ; Yan-ling ZHANG
China Journal of Chinese Materia Medica 2014;39(24):4839-4843
The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A
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metabolism
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Animals
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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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Hydrophobic and Hydrophilic Interactions
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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chemistry
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pharmacology
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Lipid Metabolism
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drug effects
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Lipids
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blood
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Medicine, Chinese Traditional
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Models, Molecular
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Quantitative Structure-Activity Relationship
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Technology
9.Protective effect of ethyl acetate extract of Pongamia pinnata roots on ethanol-induced gastric mucosal injuries in rats
Keyun LIU ; Yi ZHU ; Zhi DONG ; Jing LI ; Ling HUANG ; Guobiao CHEN
Chinese Journal of Pharmacology and Toxicology 2007;21(6):476-481
AIM To investigate the therapeutic effect of ethyl acetate extract from Pongamia pinnata roots (PREA) on ethanol-induced gastric lesions. METHODS The experimental gastric mucosal injuries were prepared by ig ethanol to rats, and the protective effect of PREA was evaluated by calculating lesion index, observing pathological changes, and measuring the contents of nitric oxide (NO) and malondialdehyde (MDA), and the activity of superoxide dismutase (SOD) from gastric mucosal tissue. In addition, gastric secretary and gastric wall adherent mucus were studied with the pylorus-ligation rat model. RESULTSCompared with the model control group, PREA (50, 150 and 450 mg·kg-1, ig) dose-dependently prevented the gastric mucosal damages induced by ethanol, its inhibition rates were 28.7%, 57.7% and 78.7 %, respectively. The pathomorphology lesions of mucosal tissue were obviously ameliorated. PREA obviously antagonized the ethanol-induced elevation of MDA content, and reduction of NO level and SOD activity of gastric mucosa. PREA significantly reduced gastric juice volume, free acidity, total acidity and total acid output, but didn′t affect the pepsin activity. Moreover, PREA obviously increased adherent mucus quantity of stomach wall, as well as free mucus quantity dissolved in gastric juice of pylorus-ligation rat. CONCLUSIONPREA has protective effect on ethanol-induced gastric mucosal injuries, which suggests that PREA may be used for protection or treatment of human ethanolinduced gastric lesions.
10.Research on genetic stability to American ginseng introduced into China for 30 years.
Xiao-Yu WEI ; Yi-Xin TIAN ; Zhi-Ling ZHAO ; Wei WEI
China Journal of Chinese Materia Medica 2014;39(19):3723-3726
To study the genetic stability of Panax quinquefolium after introduced into China for 30 years, the samples of P. quinquefolium from 14 regions of China were studied. RAPD molecular marker technology was applied in this research, and POPGEN32 data analysis and NTSYS2. 10 cluster diagram were used to analyze the data. The results showed that there are abundant genetic diversity in the ginseng samples. There were 81 polymorphic bands based on the 13 random primers. The polymorphism was 83.51%, the effective number of alleles (N(e)) was 1.456 7; Nei's gene diversity index (H) was 0.274 8; Shannon's diversity index (H(o)) was 0.419 4. The clustering analyses indicated that P. quinquefolium and P. ginseng were classified into two obvious groups, especially, it was also found that the P. quinquefolium could be divided into two obvious groups based on whether the P. ginseng was cultivated in the same region or not, but it was thought that there was not genetically a qualitative difference. Thus it suggests that a good breeding field should be established in Jilin Province of China for the germplasm purification.
China
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DNA, Plant
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genetics
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Genetic Variation
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Introduced Species
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Panax
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classification
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genetics
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Phylogeny
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Polymorphism, Genetic
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Random Amplified Polymorphic DNA Technique
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United States