AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stres...AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS： We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress （WRS） with or without （A） inhibition of cyclooxygenase （COX）-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, （B） suppression of NO-synthase with L-NNA （20 mg/kg ip）, and （C） inactivation by capsaicin （125 mg/kg sc） of sensory nerves with or without intragastric （ig） pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow （GBF） was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase （SOD） activity and malonyldialdehyde （MDA） concentration, as an index of lipid peroxidation were determined. RESULTS： Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE （8-64 mg/kg i g） dose- dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% （ID50） was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog （5 μg/kg i g）. GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating IVlDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Cotreatment of exogenous calcitonine gene-related peptide （CGRP） with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION： GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.展开更多
孕烷X受体(pregnane X receptor,PXR)是核受体超家族的成员之一,其本质是配体激活型转录因子。PXR高表达于肝脏和肠道,在肾脏和脑等器官也有表达。自发现以来,PXR就被公认为是外源物质和内源物质的感受器,在激活状态下,可以调节药物代...孕烷X受体(pregnane X receptor,PXR)是核受体超家族的成员之一,其本质是配体激活型转录因子。PXR高表达于肝脏和肠道,在肾脏和脑等器官也有表达。自发现以来,PXR就被公认为是外源物质和内源物质的感受器,在激活状态下,可以调节药物代谢酶、转运蛋白和其他代谢相关蛋白质的表达,从而起到解毒等作用。由于PXR高表达于肝脏和肠道,所以其在消化系统的功能被大量研究报道。近年来,随着PXR在越来越多的脑区被检测到,其在中枢神经系统中的生理和病生理功能被广泛关注。本文主要就PXR在中枢神经系统的表达谱、在血脑屏障中的功能,以及其与神经疾病和神经毒性的关系,与行为学的相关性等进行综述。上述内容一方面可指导临床合理用药,另一方面可拓展科研工作者新药研发的思路;同时,也为未来PXR在中枢神经系统中功能的进一步研究提供了理论基础和方法思路。展开更多
Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma t...Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.展开更多
文摘AIM： Grapefruit-seed extract （GSE） containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS： We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress （WRS） with or without （A） inhibition of cyclooxygenase （COX）-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, （B） suppression of NO-synthase with L-NNA （20 mg/kg ip）, and （C） inactivation by capsaicin （125 mg/kg sc） of sensory nerves with or without intragastric （ig） pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow （GBF） was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase （SOD） activity and malonyldialdehyde （MDA） concentration, as an index of lipid peroxidation were determined. RESULTS： Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE （8-64 mg/kg i g） dose- dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% （ID50） was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog （5 μg/kg i g）. GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating IVlDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Cotreatment of exogenous calcitonine gene-related peptide （CGRP） with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION： GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.
文摘孕烷X受体(pregnane X receptor,PXR)是核受体超家族的成员之一,其本质是配体激活型转录因子。PXR高表达于肝脏和肠道,在肾脏和脑等器官也有表达。自发现以来,PXR就被公认为是外源物质和内源物质的感受器,在激活状态下,可以调节药物代谢酶、转运蛋白和其他代谢相关蛋白质的表达,从而起到解毒等作用。由于PXR高表达于肝脏和肠道,所以其在消化系统的功能被大量研究报道。近年来,随着PXR在越来越多的脑区被检测到,其在中枢神经系统中的生理和病生理功能被广泛关注。本文主要就PXR在中枢神经系统的表达谱、在血脑屏障中的功能,以及其与神经疾病和神经毒性的关系,与行为学的相关性等进行综述。上述内容一方面可指导临床合理用药,另一方面可拓展科研工作者新药研发的思路;同时,也为未来PXR在中枢神经系统中功能的进一步研究提供了理论基础和方法思路。
文摘Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.
