Objective:To interpret the pharmacology of quercetin in treatment of atherosclerosis(AS).Methods:Fourteen apolipoprotein E-deficient(ApoE^(-/-))mice were divided into 2 groups by a random number table:an AS model(ApoE...Objective:To interpret the pharmacology of quercetin in treatment of atherosclerosis(AS).Methods:Fourteen apolipoprotein E-deficient(ApoE^(-/-))mice were divided into 2 groups by a random number table:an AS model(ApoE^(-/-))group and a quercetin treatment group(7 in each).Seven age-matched C57 mice were used as controls(n=7).Quercetin[20 mg/(kg·d)]was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation.Besides morphological observation,the distribution of CD11b,F4/80,sirtuin 1(Sirt1)and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence.Ultra-performance liquid chromatography/tandem mass spectrometry(UPLC-MSC/MS)was performed to study the pharmacology of quercetin against AS.Then,simultaneous administration of an apelin receptor antagonist(ML221)with quercetin was conducted to verify the possible targets of quercetin.Key proteins in apelin signaling pathway,such as angiotensin domain type 1 receptor-associated proteins(APJ),AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α),tissue plasminogen activator(TPA),uncoupling protein 1(UCP1)and angiotensinⅡreceptor 1(AT1R),were assayed by Western blot.Results:Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^(-/-)aortas in vivo.Quercetin decreased the densities of CD11b,F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE^(-/-)mice(all P<0.05).Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls.Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways.Quercetin treatment increased the protein expressions of APJ,AMPK,PGC-1α,TPA and UCP1,while decreased the AT1R level(all P<0.05).After the apelin pathway was blocked by ML221,the effect of quercetin was abated significantly,confirming that quercetin attenuated AS by modulating the apelin signaling pathway(all P<0.05).Conclusion:Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.展开更多
Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present ...Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats(SHRs) and its protective effects against Ang Ⅱ induced injury in human umbilical vein endothelial cells(HUVECs). SHRs were administered intragastrically with TT(17.2 or 8.6 g·kg^(-1)·d^(-1)) for 6 weeks, using valsartan(13.5 mg·kg^(-1)·d^(-1)) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang Ⅱ, endothelin^(-1)(ET^(-1)), superoxide dismutase(SOD) and malonaldehyde(MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10–6 mol·L^(-1) Ang Ⅱ. Cell Apoptosisapoptosis, intracellular reactive oxygen species(ROS) was assessed. Endothelial nitric oxide synthase(eN OS), ET^(-1), SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang Ⅱ, ET^(-1), NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang Ⅱ-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mR NA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.展开更多
基金Supported by Shandong Province'Taishan Scholar'Construction Project Funds (No.2018-35)。
文摘Objective:To interpret the pharmacology of quercetin in treatment of atherosclerosis(AS).Methods:Fourteen apolipoprotein E-deficient(ApoE^(-/-))mice were divided into 2 groups by a random number table:an AS model(ApoE^(-/-))group and a quercetin treatment group(7 in each).Seven age-matched C57 mice were used as controls(n=7).Quercetin[20 mg/(kg·d)]was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation.Besides morphological observation,the distribution of CD11b,F4/80,sirtuin 1(Sirt1)and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence.Ultra-performance liquid chromatography/tandem mass spectrometry(UPLC-MSC/MS)was performed to study the pharmacology of quercetin against AS.Then,simultaneous administration of an apelin receptor antagonist(ML221)with quercetin was conducted to verify the possible targets of quercetin.Key proteins in apelin signaling pathway,such as angiotensin domain type 1 receptor-associated proteins(APJ),AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α),tissue plasminogen activator(TPA),uncoupling protein 1(UCP1)and angiotensinⅡreceptor 1(AT1R),were assayed by Western blot.Results:Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE^(-/-)aortas in vivo.Quercetin decreased the densities of CD11b,F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE^(-/-)mice(all P<0.05).Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls.Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways.Quercetin treatment increased the protein expressions of APJ,AMPK,PGC-1α,TPA and UCP1,while decreased the AT1R level(all P<0.05).After the apelin pathway was blocked by ML221,the effect of quercetin was abated significantly,confirming that quercetin attenuated AS by modulating the apelin signaling pathway(all P<0.05).Conclusion:Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.
基金supported by Shandong Province‘Taishan Scholar’Construction Project Funds(No.2012-55)the National Natural Science Foundation of China(No.81573916)
文摘Angiotensin Ⅱ(Ang Ⅱ) is involved in endothelium injury during the development of hypertension. Tribulus terrestris(TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats(SHRs) and its protective effects against Ang Ⅱ induced injury in human umbilical vein endothelial cells(HUVECs). SHRs were administered intragastrically with TT(17.2 or 8.6 g·kg^(-1)·d^(-1)) for 6 weeks, using valsartan(13.5 mg·kg^(-1)·d^(-1)) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang Ⅱ, endothelin^(-1)(ET^(-1)), superoxide dismutase(SOD) and malonaldehyde(MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10–6 mol·L^(-1) Ang Ⅱ. Cell Apoptosisapoptosis, intracellular reactive oxygen species(ROS) was assessed. Endothelial nitric oxide synthase(eN OS), ET^(-1), SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang Ⅱ, ET^(-1), NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang Ⅱ-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mR NA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.
