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1.
2.
Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy
Ambreen Shoaib Badruddeen Rakesh Kumar Dixit Magdah Ganash George Barreto Ghulam Md Ashraf Hefazat Hussain Siddiqui 《Journal of cellular biochemistry》2019,120(10):16524-16532
Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications. 相似文献
3.
Interaction of human thrombospondin with types I-V collagen: direct binding and electron microscopy 总被引:14,自引:9,他引:5
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N J Galvin P M Vance V M Dixit B Fink W A Frazier 《The Journal of cell biology》1987,104(5):1413-1422
Binding of thrombospondin (TSP) to types I-V collagen was examined by direct binding assays using 125I-TSP and by visualization of rotary-shadowed intermolecular complexes in the electron microscope. The binding of TSP was highest to type V collagen in the absence of Ca, while lower but significant levels of binding were observed to all other collagen types in the presence or absence of Ca. Unlike intact TSP, the trimeric collagen-binding domain of TSP composed of 70-kD chains showed no Ca dependence in its binding to type V collagen. Further evidence for binding of TSP to types I and III collagen was obtained by competition studies in which these soluble collagens effectively inhibited binding of 125I-TSP to immobilized type V collagen. The binding of TSP to type V collagen was inhibited by heparin and fucoidin, both high-affinity ligands of TSP's heparin-binding domain. mAb A6.1, which binds to the 70-kD domain of TSP, is also the best of a panel of anti-TSP mAbs at inhibiting the TSP-collagen interaction. Electron microscopy of rotary-shadowed replicas of TSP-collagen complexes revealed that all five types of collagen examined had a binding site for TSP at one end of the pepsinized, triple helical molecule. The specificity of this site was tested by examining the ability of BSA to form a complex with the end of the pepsinized collagens. Rotary-shadowed replicas revealed a low frequency of apparent BSA-collagen complexes, and histograms of these data showed no evidence for the preferential association of BSA with the end of the collagen molecules. In addition to the specific end site, type V collagen had an internal binding site for TSP located about two-thirds of the distance along the length of the collagen molecule from the end site. The internal binding site for TSP on type V collagen is apparently the site responsible for the higher affinity binding of TSP to that protein observed in direct binding assays. The trimeric 70-kD collagen-binding domain of TSP bound to the same sites on the collagens as did intact TSP. 相似文献
4.
Y K Gupta P Bhandari A Chugh S D Seth K S Dixit K P Bhargava 《Indian journal of experimental biology》1989,27(1):52-54
The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report. 相似文献
5.
P K Dixit M Smithberg 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1988,187(1):2-6
The effect of lithium ion on glucose oxidation in the cerebrum and cerebellum of mice was measured in vitro by the conversion of isotopic glucose into 14CO2/mg wet weight. Glucose utilization is unaffected by lowest lithium dosage but is inhibited by high lithium concentrations (197-295 mM). Chronic administration of lithium to adult mice decreased the DNA content of the cerebrum and cerebellum at concentrations of 80 and 108 mM. The DNA content of selected postnatal stages of cerebrum and cerebellum was measured starting on Day 1 or 2. This served as another parameter to evaluate glucose oxidation studies at these ages. On the basis of wet weight, both brain parts of neonates of ages 1 and 10 days were approximately one-half that of the adult counterparts. On the basis of DNA content, the cerebrum enhanced its glucose utilization twofold from Day 1 to Day 10 and tripled its utilization from Day 10 to Day 20. The glucose utilization by cerebrum at Day 20 is similar to adult values. In contrast, glucose oxidation in the cerebellum remained relatively constant throughout the postnatal growth. The relative susceptibility of the two brain parts is discussed. 相似文献
6.
Thrombospondin (TSP) is a glycoprotein secreted from the alpha-granules of platelets upon activation. In the presence of divalent cations, the secreted protein binds to the surface of the activated platelets and is responsible for the endogenous lectin-like activity associated with activated platelets. Platelets fixed with formaldehyde following activation by thrombin are agglutinated by exogenously added TSP. Fixed, nonactivated platelets are not agglutinated. The platelet agglutinating activity of TSP is optimally expressed in the presence of 2 mM each of Mg2+ and Ca2+. Reduction of the disulfide bonds within the TSP molecule inhibits its platelet agglutinating activity. TSP bound to the surface of fixed, activated platelets can be eluted by the addition of disodium ethylenediaminetetraacetate. This approach was exploited to identify the region of the TSP molecule containing the platelet binding site. The binding site resides within a thermolytic fragment of TSP with Mr 140 000 but is not present in the Mr 120 000 fragment derived from the polypeptide of Mr 140 000. Since both the Mr 140 000 and 120 000 fragments contain fibrinogen binding sites, this finding suggests that the binding of TSP to the platelet surface requires interaction with other platelet surface components in addition to fibrinogen. The observation that fibrinogen only partially inhibits the TSP-mediated agglutination of fixed, activated platelets is consistent with this interpretation. 相似文献
7.
Mapping of epitopes for monoclonal antibodies against human platelet thrombospondin with electron microscopy and high sensitivity amino acid sequencing 总被引:21,自引:13,他引:8
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N J Galvin V M Dixit K M O'Rourke S A Santoro G A Grant W A Frazier 《The Journal of cell biology》1985,101(4):1434-1441
A panel of monoclonal antibodies (Mab's) has been raised against human platelet thrombospondin (TSP). One Mab, designated A2.5, inhibits the hemagglutinating activity of TSP and immunoprecipitates the NH2 terminal 25 kD heparin binding domain of TSP (Dixit, V.M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Biochemistry, in press). Another Mab, C6.7, blocks the thrombin-stimulated aggregation of live platelets and immunoprecipitates an 18-kD fragment distinct from the heparin binding domain (Dixit, V. M., D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, and W. A. Frazier, 1985, Proc. Natl. Acad. Sci. 82: 3472-3476). To determine the relative locations of the epitopes for these Mabs in the three-dimensional structure of TSP, we have examined TSP-Mab complexes by electron microscopy of rotary-shadowed proteins. The TSP molecule is composed of three 180-kD subunits, each of which consists of a small globular domain (approximately 8 nm diam) and a larger globular domain (approximately 16 nm diam) connected by a thin, flexible strand. The subunit interaction site is on the thin connecting strands, nearer the small globular domains. Mab A2.5 binds to the cluster of three small domains, indicating that this region contains the heparin binding domain and thus represents the NH2 termini of the TSP peptide chains. Mab C6.7 binds to the large globular domains on the side opposite the point at which the connecting strand enters the domain, essentially the maximum possible distance from the A2.5 epitope. Using high sensitivity automated NH2 terminal sequencing of TSP chymotryptic peptides we have ordered these fragments within the TSP peptide chain and have confirmed that the epitope for C6.7 in fact lies near the extreme COOH terminus of the peptide chain. In combination with other data, we have been able to construct a map of the linear order of the identified domains of TSP that indicates that to a large extent, the domains are arranged co-linearly with the peptide chain. 相似文献
8.
Localization of the hemagglutinating activity of platelet thrombospondin to a 140 000-dalton thermolytic fragment 总被引:11,自引:0,他引:11
The platelet protein thrombospondin (TSP) which is secreted from alpha-granules upon platelet activation agglutinates trypsinized, glutaraldehyde-fixed human erythrocytes. Optimal conditions for the hemagglutinating activity require that both Ca2+ and Mg2+ be present in final concentrations of 2 mM. In the presence of dithiothreitol (i.e., reduction of disulfide bonds), the lectin-like activity decreases in a manner proportional to the extent of reduction of the molecule from its native trimeric configuration into its Mr 180 000 subunits. Proteolysis of purified TSP with thermolysin, which produces discrete domains with the capacity to bind fibrinogen and heparin, also diminishes, but does not abolish, the hemagglutinating activity. Fibrinogen was without effect on hemagglutinating activity while heparin was found to be a potent inhibitor. Other proteoglycans such as hyaluronic acid, chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate had no effect. That portion of the TSP molecule apparently responsible for the hemagglutinating activity was identified by incubating a thermolytic digest of TSP with red blood cells and then determining which fragment was bound to the cell surface. The binding site resides within a peptide fragment of 140 000 daltons but is absent from an Mr 120 000 fragment derived from the Mr 140 000 fragment. Under the conditions for optimal expression of hemagglutinating activity (i.e., 2 mM MgCl2 and 2 mM CaCl2), this Mr 140 000 fragment was also shown to have heparin binding activity. 相似文献
9.
Extract of alfalfa seed (ethanolic 50 % v/v) prevents the development of plaque formation and hyperlipidaemia in cholesterol
fed rabbits. It inhibits the elevation of serum total cholesterol, triglycerides, phospholipids, LDL-cholesterol and total
cholesterol/phospholipid ratio, while HDL-cholesterol/total cholesterol ratio increases, which is associated with a reduced
incidence of atherosclerosis. Further reduction in total cholesterol and phospholipid contents of liver and heart muscle are
suggestive of a beneficial role of the seed extract. The possible mechanisms of action are discussed. 相似文献
10.