Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature.Quercetin is a natural flavonoid and has a variety of pharmacological e...Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature.Quercetin is a natural flavonoid and has a variety of pharmacological effects including improvement of endothelial cell function.However,its pharmacological effects on pulmonary hypertension have been rarely reported.We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH.We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group:the monocrotaline group,the quercetin group and the control group.We found that,compared with the controls,the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index in the monocrotaline group were significantly higher (P < 0.01).Quercetin caused a significant reduction both in the mPAP and right ventricular hypertrophy index compared with the monocrotaline group (P < 0.01) while no difference was found between the quercetin group and the control group (P > 0.05).Monocrotaline induced a marked increase in the wall thickness (WT) in small and mid-sized pulmonary arteries compared with the controls (P < 0.01).Monocrotaline also induced a marked increase in the wall area (WA) in small [(56.38±6.65)% in monocrotaline vs.(19.80±4.63)% in control] and mid-sized [(43.71±5.38)% in monocrotaline vs.(14.24±3.66)% in control] pulmonary arteries (P < 0.01).Quercetin treatment markedly reduced monocrotaline induced increase in both WT and WA (P < 0.01),which,however,still remained significantly elevated compared with those of the controls (P < 0.01).Furthermore,compared with controls,proliferating cell nuclear antigen (PCNA) expression in the pulmonary artery tissues was markedly increased by monocrotaline [(45.59±1.27) in monocrotaline vs.(9.64±0.69) in controls],which was significantly attenuated by quercetin.Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.展开更多
A series of 2-[1-(2-formylamido-3-phenylpropionyloxy)alkyl]-1,4-dihydroxy-9,10-anthraquinone(2FPADHAQ) derivatives was designed and synthesized.Their antitumor activities were tested against L1210 tumor cells and P388...A series of 2-[1-(2-formylamido-3-phenylpropionyloxy)alkyl]-1,4-dihydroxy-9,10-anthraquinone(2FPADHAQ) derivatives was designed and synthesized.Their antitumor activities were tested against L1210 tumor cells and P388 mouse leukemic tumor cells in vitro and in ICR mice bearing sarcoma 180 cells in vivo.Overall,the introduction of 2-formylamido-3-phenyl-propanoic acid(2-FPPA) into the C-2-alkyl side chain C'-1 hydroxy group in 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones(2-HDHAQ) enhanced the antitumor activity compared with the starting materials.2-FPADHAQ with alkyl chains longer than the pentyl group had negligible activity,whereas compounds 2b,2c,2d and 2e possessing shorter chains demonstrated moderate cytotoxic activity[50% effective dose(ED 50) of L1210 and P388 are 2.61―4.75 and 5.84―8.74 μg/mL],whereas compound 2l with an aromatic system showed strong cytotoxic activity.T/C(%) values[(average survival days in the test group)/(average survival days in the control group)×100%] also show that the introduction of 2-FPPA into the side chain of 2-HDHAQ enhanced antitumor activity.These data suggest that the introduction of an amino acid into the starting material may increase its affinity for DNA or its selectivity for proliferating cancer cells.展开更多
文摘Pulmonary arterial hypertension (PAH) is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature.Quercetin is a natural flavonoid and has a variety of pharmacological effects including improvement of endothelial cell function.However,its pharmacological effects on pulmonary hypertension have been rarely reported.We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH.We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group:the monocrotaline group,the quercetin group and the control group.We found that,compared with the controls,the mean pulmonary artery pressure (mPAP) and the right ventricular hypertrophy index in the monocrotaline group were significantly higher (P < 0.01).Quercetin caused a significant reduction both in the mPAP and right ventricular hypertrophy index compared with the monocrotaline group (P < 0.01) while no difference was found between the quercetin group and the control group (P > 0.05).Monocrotaline induced a marked increase in the wall thickness (WT) in small and mid-sized pulmonary arteries compared with the controls (P < 0.01).Monocrotaline also induced a marked increase in the wall area (WA) in small [(56.38±6.65)% in monocrotaline vs.(19.80±4.63)% in control] and mid-sized [(43.71±5.38)% in monocrotaline vs.(14.24±3.66)% in control] pulmonary arteries (P < 0.01).Quercetin treatment markedly reduced monocrotaline induced increase in both WT and WA (P < 0.01),which,however,still remained significantly elevated compared with those of the controls (P < 0.01).Furthermore,compared with controls,proliferating cell nuclear antigen (PCNA) expression in the pulmonary artery tissues was markedly increased by monocrotaline [(45.59±1.27) in monocrotaline vs.(9.64±0.69) in controls],which was significantly attenuated by quercetin.Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.
基金Supported by the National Natural Science Foundation of China(No.30360119)
文摘A series of 2-[1-(2-formylamido-3-phenylpropionyloxy)alkyl]-1,4-dihydroxy-9,10-anthraquinone(2FPADHAQ) derivatives was designed and synthesized.Their antitumor activities were tested against L1210 tumor cells and P388 mouse leukemic tumor cells in vitro and in ICR mice bearing sarcoma 180 cells in vivo.Overall,the introduction of 2-formylamido-3-phenyl-propanoic acid(2-FPPA) into the C-2-alkyl side chain C'-1 hydroxy group in 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones(2-HDHAQ) enhanced the antitumor activity compared with the starting materials.2-FPADHAQ with alkyl chains longer than the pentyl group had negligible activity,whereas compounds 2b,2c,2d and 2e possessing shorter chains demonstrated moderate cytotoxic activity[50% effective dose(ED 50) of L1210 and P388 are 2.61―4.75 and 5.84―8.74 μg/mL],whereas compound 2l with an aromatic system showed strong cytotoxic activity.T/C(%) values[(average survival days in the test group)/(average survival days in the control group)×100%] also show that the introduction of 2-FPPA into the side chain of 2-HDHAQ enhanced antitumor activity.These data suggest that the introduction of an amino acid into the starting material may increase its affinity for DNA or its selectivity for proliferating cancer cells.
