Progress in anti-inflammatory effects of escin

The fraction of horse chestnut seeds was named escins,which mainly consists of A,B,C,and D escin.Accumulating evidence suggests that escin exerts potent anti-inflammatory and anti-edematous effects.The effects of escin on inflammation and edema have been confirmed in various models.In a study in 1961,intravenous administration of escin was found to reduce acute edema in a rat paw.In the same study,escin was found to inhibit the increase in vascular permeability induced by egg white injection.Escin dose-dependently reduced the capillary permeability in chloroform-induced local inflammation in the abdominal skin surface of rabbits.The anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats.Escin gel decreased the contents of PGE2,TNF-α,and IL^(-1)β,and reduced the raw edema and capillary permeability.The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to investigate the anti-inflammatory effects of escin and glucocorticoid alone or combined.Co-administration of escin with cortisone significantly reduced the volume of exudates and the number of white blood cells of exudates.The findings suggest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect.The anti-inflammatory effect of escin was investigated in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice.Escin showed an anti-inflammatory effect,which is similar to that seen with dexamethasone treatment.However,escin showed a longer duration of the anti-inflammatory response than that of dexamethasone.Furthermore,escin had no significant effects on spleen index,thymus index,proliferative capacity of splenocytes,lymphocyte count,and phagocytic rate.The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects without any immunosuppressive effects.Traditionally the mechanism of anti-inflammatory effect of escin is supposed to be relative to release of PGF2αand corticosterone.The early studies showed that escin might promote the release of PGF2αand affect the pituitary adrenal system,stimulate the release of adrenocorticotropic hormone(ACTH)and glucocorticoid,which may explain its anti-inflammatory and anti-edema effects.Escin has glucocorticoid-like anti-inflammatory effect.However,escin did not exhibit an anti-inflammatory effect in low dose.Combination of suboptimal concentrations of escin with corticosterone inhibited the release of inflammatory factors including NO,TNF-αand IL^(-1)βin the LPS-stimulated macrophage cells.Previous studies demonstrate that escin combined with glucocorticoid produced synergistic anti-inflammatory effects.The potential synergistic mechanisms may be associated with the property which escin regulates the glucocorticoid receptor(GR)signaling pathway.Escin can upregulate the expression of GR,promote the combination of glucocorticoid and GR,then promote the activated GR transfer into the nucleus.Activated GR will inhibit the activation of NF-κB directly,thus further inhibiting the expression of TNF-αand IL^(-1)βand other inflammatory factors.Escin could inhibit 11β-HSD2 but not 11β-HSD1,thus decrease the metabolism of glucocorticoid.Escin and glucocorticoids have similar chemical structures.This indicate that one of the anti-inflammatory mechanisms of escin may be due to its stimulating GR by binding to it.Eacin might be a partial agonist of GR.A good many of researches have demonstrated the anti-inflammatory properties of escin,and shed light on the underlying mechanisms by which escin exerts these effects.Escin,as an oral or intravenous formulation,or a topical gel,inhibits inflammation,producing measurable improvements in edema and acute lung injury.Further clinical studies of escin are needed to demonstrate these properties in larger patient populations.

Application of binding theory for seepage of viscoelastic fluid in a variable diameter capillary

The polymer solution for polymer flooding is a viscoelastic fluid. There exist both shear flow and elongational flow when the polymer solution flows in a porous medium, where an additional dissipation is involved. The additional dissipation caused by elongational deformation is often ignored while studying the flow of the fluid in a porous medium. For a complex polymer solution, the generated elongational pressure drop cannot be ignored. In a capillary of fixed diameter, the polymer solution is only impacted by the shear force, and its rheological property is pseudoplastic. Therefore the variable diameter capillary and the converging-diverging flow model with different cross sections are required to describe the flow characteristics of the polymer solution in porous media more accurately. When the polymer solution flows through the port, we have the elongational flow and the polymer molecules undergo elongational deformation elastically. By using the mechanical energy balance principle and the minimum energy principle, a mathematical model of non-Newtonian fluid inlet flow was established by Binding. On the basis of the Binding theory, with the application of the theory of viscoelastic fluid flow in the circular capillary and the contraction-expansion tube, the relations between the viscoelastic fluid flow rate and the pressure drop are obtained.

Unfractionated heparin attenuates endothelial barrier dysfunction via the phosphatidylinositol-3 kinase/serine/threonine kinase/nuclear factor kappa-B pathway

Background::Vascular endothelial dysfunction is considered a key pathophysiologic process for the development of acute lung injury.In this study,we aimed at investigating the effects of unfractionated heparin(UFH)on the lipopolysaccharide(LPS)-induced changes of vascular endothelial-cadherin(VE-cadherin)and the potential underlying mechanisms.Methods::Male C57BL/6 J mice were randomized into three groups:vehicle,LPS,and LPS+UFH groups.Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis.Mice in the LPS+UFH group received subcutaneous injection of 8 U UFH 0.5 h before LPS injection.The lung tissue of the mice was collected for assessing lung injury by measuring the lung wet/dry(W/D)weight ratio and observing histological changes.Human pulmonary microvascular endothelial cells(HPMECs)were cultured and used to analyze the effects of UFH on LPS-or tumor necrosis factor-alpha(TNF-α)-induced vascular hyperpermeability,membrane expression of VE-cadherin,p120-catenin,and phosphorylated myosin light chain(p-MLC),and F-actin remodeling,and on the LPS-induced activation of the phosphatidylinositol-3 kinase(PI3K)/serine/threonine kinase(Akt)/nuclear factor kappa-B(NF-κB)signaling pathway.Results::In vivo,UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes(neutrophil infiltration and erythrocyte effusion,alveolus pulmonis collapse,and thicker septum),decreased the lung W/D,and increased protein concentration(LPS vs.LPS+UFH:0.57±0.04 vs.0.32±0.04 mg/mL,P=0.0092),total cell count(LPS vs.LPS+UFH:9.57±1.23 vs.3.65±0.78×105/mL,P=0.0155),polymorphonuclear neutrophil percentage(LPS vs.LPS+UFH:88.05%±2.88%vs.22.20%±3.92%,P=0.0002),and TNF-α(460.33±23.48 vs.189.33±14.19 pg/mL,P=0.0006)in the bronchoalveolar lavage fluid.In vitro,UFH pre-treatment prevented the LPS-induced decrease in the membrane expression of VE-cadherin(LPS vs.LPS+UFH:0.368±0.044 vs.0.716±0.064,P=0.0114)and p120-catenin(LPS vs.LPS+UFH:0.208±0.018 vs.0.924±0.092,P=0.0016),and the LPS-induced increase in the expression of p-MLC(LPS vs.LPS+UFH:0.972±0.092 vs.0.293±0.025,P=0.0021).Furthermore,UFH attenuated LPS-and TNF-α-induced hyperpermeability of HPMECs(LPS vs.LPS+UFH:8.90±0.66 vs.15.84±1.09Ω·cm 2,P=0.0056;TNF-αvs.TNF-α+UFH:11.28±0.64 vs.18.15±0.98Ω·cm 2,P=0.0042)and F-actin remodeling(LPS vs.LPS+UFH:56.25±1.51 vs.39.70±1.98,P=0.0027;TNF-αvs.TNF-α+UFH:55.42±1.42 vs.36.51±1.20,P=0.0005)in vitro.Additionally,UFH decreased the phosphorylation of Akt(LPS vs.LPS+UFH:0.977±0.081 vs.0.466±0.035,P=0.0045)and I kappa B Kinase(IKK)(LPS vs.LPS+UFH:1.023±0.070 vs.0.578±0.044,P=0.0060),and the nuclear translocation of NF-κB(LPS vs.LPS+UFH:1.003±0.077 vs.0.503±0.065,P=0.0078)in HPMECs,which was similar to the effect of the PI3K inhibitor,wortmannin.Conclusions::The protective effect of UFH against LPS-induced pulmonary endothelial barrier dysfunction involves VE-cadherin stabilization and PI3K/Akt/NF-κB signaling.

Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine myocardium

Background Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine the effects of low-power He-Ne laser irradiation directed at the precardial region of Wistar rats on capillary permeability in the myocardium and the expression of myocardial vascular endothelial growth factor (VEGF). Methods Sixteen rats were divided randomly into control and irradiated groups (n=8, each). A He-Ne laser (632.8 nm) was applied to the irradiated group with a dose of 60.5 J/cm2. Ferritin was perfused into the left femoral vein and capillary permeability was examined under an electron microscope. VEGF expression in the myocardium was investigated by immunohistochemical methods, RT-PCR, and image analysis. Results The ultrastructures of the myocardial capillaries were examined. Compared to the control group, more high-density granules (ferritin), which were present within the capillary endothelium and the mitochondrions of myocardial cells in the internal layer of the myocardium, were observed in the irradiated group. VEGF staining of the myocardium was stronger in the irradiated group than that in the control group. The optic density of the irradiated group (0.246±0.015) was significantly higher than that of the control group (0.218±0.012, P<0.05). Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in irradiated rats than in the control rats.Conclusions Our study demonstrates that He-Ne laser irradiation (in doses of 60.5 J/cm2) increases myocardial capillary permeability and the production of VEGF in myocardial microvessels and in myocardium. Our study provides experimental morphological evidence that myocardial microcirculation can be improved using He-Ne laser irradiation.