AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or ca...AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS： Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups （0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05）. In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION： Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation.展开更多
Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, es...Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.展开更多
The antioxidative capacity of astaxanthin and enzyme activity of reactive oxygen eliminating enzymes such as superoxide dismutase (SOD),peroxidase (POD),catalase (CAT) and ascorbate peroxidase (APX) were studied in th...The antioxidative capacity of astaxanthin and enzyme activity of reactive oxygen eliminating enzymes such as superoxide dismutase (SOD),peroxidase (POD),catalase (CAT) and ascorbate peroxidase (APX) were studied in three cell types of Haematococcus pluvialis exposed to high concentrations of a superoxide anion radical (O2ˉ).The results show that defensive enzymes and astaxanthin-related mechanisms were both active in H.pluvialis during exposure to reactive oxygen species (ROS) such as Oˉ2.Astaxanthin reacted with ROS much faster than did the protective enzymes,and had the strongest antioxidative capacity to protect against lipid peroxidation.The defensive mechanisms varied significantly between the three cell types and were related to the level of astaxanthin that had accumulated in those cells.Astaxanthin-enriched red cells had the strongest antioxidative capacity,followed by brown cells,and astaxanthin-deficient green cells.Although there was no significant increase in expression of protective enzymes,the malondialdehyde (MDA) content in red cells was sustained at a low level because of the antioxidative effect of astaxanthin,which quenched Oˉ2 before the protective enzymes could act.In green cells,astaxanthin is very low or absent;therefore,scavenging of ROS is inevitably reliant on antioxidative enzymes.Accordingly,in green cells,these enzymes play the leading role in scavenging ROS,and the expression of these enzymes is rapidly increased to reduce excessive ROS.However,because ROS were constantly increased in this study,the enhance enzyme activity in the green cells was not able to repair the ROS damage,leading to elevated MDA content.Of the four defensive enzymes measured in astaxanthin-deficient green cells,SOD eliminates Oˉ2,POD eliminates H2O2,which is a by-product of SOD activity,and APX and CAT are then initiated to scavenge excessive ROS.展开更多
Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and dige...Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little infor- mation is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on spleno- cyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell （CRBC） method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antiturnor effects of SCP might be achieved by im- proving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.展开更多
Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making...Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making the models of ischemia and reperfusion by clamping superior mesenteric artery, the concentration of NO and SOD in the blood was examined before clamping the artery and reperfusion for 0, 30, 60 min, 1, 3, and 7 d. The expression of Bax, Bal-2, and p53 in myocardial cell was studied by means of immunohistochemical SP method and the microstructure damage was observed under electron microscopy. Results: After clamping the superior mesenteric artery and reperfusion the concentration of NO increased continuously and reached a peak for reperfusion 7 d (P<0.01) but that of SOD decreased from 30 min to 7 d. The expression of Bax, p53 and Bcl-2 also increased obviously especially for reperfusion 30 min and 7 d following ischemia and reperfusion. After reperfusion for 30 min the positive cell rate of Bax, p53 and Bcl-2 was 53.6%, 45.9% and 67.9%, for reperfusion 7 d it was 52.4%, 43.4% and 31.9% respectively, but the positive cell rate of Bax and p53 was higher than that of Bcl-2. The result of electron microscopy observation showed mfofiliments breaked, dissolved and chromatin condensed. Conclusion: Intestinal ischemia and reperfusion of rat can induced the changes of oxygen free radical and the expression of apoptotic gene and second injury of myocardial cells.展开更多
Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, ...Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.展开更多
Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic a...Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic acids（HCAs）. The stabilities were studied in buffers at p H 1.3, p H 5.0, and p H 7.4 including the human plasma. All the compounds were found highly stable at acidic p H, but underwent hydrolysis at neutral p H. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values（t1/2）, 2c（1.21 h）〈2e（1.52 h）〈2d（1.85 h）〈2b（3.38 h）〈2a（3.88 h）, correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH3 groups. In addition, the compounds（2b–e） showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^＊＋ and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids（2a–e）, their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a ＂saturation effect＂ with the hybrid molecules in the antioxidant activities.展开更多
Objective To observe therapeutic effects of acupuncture on the mouse of hyperlipemia and to explore the mechanisms. Methods One hundred and twenty Kunming mice, male, sanitary degree, were randomly divided into normal...Objective To observe therapeutic effects of acupuncture on the mouse of hyperlipemia and to explore the mechanisms. Methods One hundred and twenty Kunming mice, male, sanitary degree, were randomly divided into normal group （n=40）, a model group （n=40）, an acupuncture group （n=20） and a medicine group （n=20）. Except the normal group, the mice were fed with high fat forage to prepare mouse hyperlipemia model. On the 15th day of modeling, serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein-cholesterol （LDL-C）, high density lipoprotein-cholesterol （HDL-C） levels were detected in 20 normal mice and 20 model mice; electroacupuncture was given at bilateral ＂Fēnglóng＂ （丰隆 ST 40）, ＂Qūchí＂ （曲池 LI 11）, ＂Sānyīnjiāo＂ （三阴交 SP 6） in the acupuncture group, once a day, for 10 consecutive days; in the medicine group, the mice were intragastrically administrated with Simvastatin, once daily , for 10 consecutive days. After the end of treatment, serum TC, TG, LDL-C, HDL-C, malondialdehyde （MDA）, nitric oxide （NO） and endothelin （ET） contents and superoxide dismutase （SOD） activities were detected in the groups. Results On the 15th day of modeling, in the model group serum TG, TC, LDL-C contents were significantly higher （all P〈0.05） and HDL-C content was significantly lower （P〈0.01） than those in the normal group. After treatment for 10 days, in the acupuncture group and the medicine group serum TG, TC, LDL-C, MDA and ET contents were significantly lower and serum HDL-C and NO contents and SOD activities were significantly higher than those in the model group （P〈0.05, P〈0.01）, and the improving action in the acupuncture group was better than that in the medicine group （P〈0.05, P〈0.01）. Conclusion Acupuncture can regulate fat metabolism, resist lipid peroxidation and protect vascular endothelial function in the mouse of hyperlipemia.展开更多
Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but diffi...Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H2O2 stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O2·- levels and construct an O2^·- reaction network. To elucidate the consequences of increased O2^·- input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca2+ levels, mitochondrial Ca^2+ uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H·-2 O2 induced a rapid increase in cellular O2 levels(>27 vs.>406 amol in 20 min), leading to increased cellular oxidizing power(evaluated by ROS levels) and decreased reducing power(evaluated by glutathione(GSH) levels). In addition, we examined the dynamics of cytosolic Ca^2+ and mitochondrial Ca^2+ by confocal laser scanning microscopy and confirmed that Ca^2+ stores in the endoplasmic reticulum were the primary source of H2O2-induced cytosolic Ca^2+ bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca^2+ signals between organelles,ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.展开更多
文摘AIM： To study the protective effect of grape procyanidins on oxidative injury induced by ethanol and carbon tetrachloride in rat hepatocytes. METHODS： Normal rat hepatocytes as well as cells damaged by ethanol or carbon tetrachloride were incubated with different doses of grape procyanidins for 24 h. Cell proliferation, apoptosis and TNFα mRNA expression were subsequently determined using MTT assay, cell death ELISA and in situ hybridization. RESULTS： Proliferative levels of the control cells from ethanol and CCh injury groups significantly decreased while apoptosis and TNFα mRNA expression significantly increased compared to the normal control and grape procyanidins co-treatment groups （0.455 ± 0.051 vs 0.318 ±0.045, P 〈 0.05）. In comparison with the normal control, 50 and 100 mg/L grape procyanidins significantly stimulated cell growth, with a better effect observed with 100 mg/L grape procyanidins. CONCLUSION： Grape procyanidins inhibit the hepatocyte damage induced by ethanol and carbon tetrachloride, and stimulate normal hepatocyte proliferation.
文摘Objective Intravenous administration of basic fibroblast growth factor （bFGF） is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF. Methods Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase （MAPK/ERK kinase, MEK）-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 （Egr-1）, an important transcription factor for endogenous bFGF. Results bFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF. Conclusion MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.
基金Supported by the National High Technology Research and Development Program of China (863 Program) (No. 2008AA09Z403)the Special Project for Marine Public Welfare Industry (No.200705010)the National Natural Science Foundation of China (No. 30771638)
文摘The antioxidative capacity of astaxanthin and enzyme activity of reactive oxygen eliminating enzymes such as superoxide dismutase (SOD),peroxidase (POD),catalase (CAT) and ascorbate peroxidase (APX) were studied in three cell types of Haematococcus pluvialis exposed to high concentrations of a superoxide anion radical (O2ˉ).The results show that defensive enzymes and astaxanthin-related mechanisms were both active in H.pluvialis during exposure to reactive oxygen species (ROS) such as Oˉ2.Astaxanthin reacted with ROS much faster than did the protective enzymes,and had the strongest antioxidative capacity to protect against lipid peroxidation.The defensive mechanisms varied significantly between the three cell types and were related to the level of astaxanthin that had accumulated in those cells.Astaxanthin-enriched red cells had the strongest antioxidative capacity,followed by brown cells,and astaxanthin-deficient green cells.Although there was no significant increase in expression of protective enzymes,the malondialdehyde (MDA) content in red cells was sustained at a low level because of the antioxidative effect of astaxanthin,which quenched Oˉ2 before the protective enzymes could act.In green cells,astaxanthin is very low or absent;therefore,scavenging of ROS is inevitably reliant on antioxidative enzymes.Accordingly,in green cells,these enzymes play the leading role in scavenging ROS,and the expression of these enzymes is rapidly increased to reduce excessive ROS.However,because ROS were constantly increased in this study,the enhance enzyme activity in the green cells was not able to repair the ROS damage,leading to elevated MDA content.Of the four defensive enzymes measured in astaxanthin-deficient green cells,SOD eliminates Oˉ2,POD eliminates H2O2,which is a by-product of SOD activity,and APX and CAT are then initiated to scavenge excessive ROS.
基金supported by the National Natural Science Foundation of China(No.30572314)the Basic Research Program of Science and Technology,Ministry of Science and Technology of China(No.2007FY210500)+1 种基金the Program of Chinese Offshore Investigation and Assessment,State Oceanic Administration of China(Nos.908-01-ST12,908-02-05-04)Science and Technology Program of Shandong Province,China(No.03BS109)
文摘Seaweed Complex Preparation （SCP） is a clinical traditional Chinese medicine preparation which is composed of seven traditional Chinese herbs, and it has been used for treatment of lung cancer, liver cancer and digestive cancer. However, little infor- mation is available about the pharmacodynamic basis. The antitumor, immunomodulatory and free radical scavenging effects of SCP were evaluated in this study. Transplanted tumor in vivo method was used to determine the antitumor effect. The effects on spleno- cyte proliferation and phagocytosis of macrophages in tumor-bearing mice were measured by the MTT method and the phagocytizing cock red blood cell （CRBC） method respectively. The scavenging activities of SCP on DPPH and hydroxyl radicals in vitro were investigated. It was found that the medium-dose and high-dose of SCP could significantly inhibit the growth of transplanted hepatic tumor of murine hepatocarcinoma cell line H22, and promote proliferation of splenocytes and phagocytosis of macrophages. SCP possessed noticeable scavenging activities on DPPH and hydroxyl radicals. The antiturnor effects of SCP might be achieved by im- proving immune system and scavenging free radicals, which is in accordance with the viewpoint of traditional Chinese medicine in promoting the body resistance and eliminating pathogenic factors for cancer treatment.
文摘Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making the models of ischemia and reperfusion by clamping superior mesenteric artery, the concentration of NO and SOD in the blood was examined before clamping the artery and reperfusion for 0, 30, 60 min, 1, 3, and 7 d. The expression of Bax, Bal-2, and p53 in myocardial cell was studied by means of immunohistochemical SP method and the microstructure damage was observed under electron microscopy. Results: After clamping the superior mesenteric artery and reperfusion the concentration of NO increased continuously and reached a peak for reperfusion 7 d (P<0.01) but that of SOD decreased from 30 min to 7 d. The expression of Bax, p53 and Bcl-2 also increased obviously especially for reperfusion 30 min and 7 d following ischemia and reperfusion. After reperfusion for 30 min the positive cell rate of Bax, p53 and Bcl-2 was 53.6%, 45.9% and 67.9%, for reperfusion 7 d it was 52.4%, 43.4% and 31.9% respectively, but the positive cell rate of Bax and p53 was higher than that of Bcl-2. The result of electron microscopy observation showed mfofiliments breaked, dissolved and chromatin condensed. Conclusion: Intestinal ischemia and reperfusion of rat can induced the changes of oxygen free radical and the expression of apoptotic gene and second injury of myocardial cells.
基金Supported by Key Project Foundation of Hebei Administration of TCM:2009058
文摘Objective To observe the effect and explore the mechanism of acupuncture on hyperlipemia in mice. Methods One hundred and twenty male Kunming mice of clean grade were randomly divided into a normal group （40 mice）, a model group （40 mice）, an acupuncture group （20 mice）, and a drug group （20 mice）. The hyperlipidemia model was prepared in the latter 3 groups by feeding with high fat diet. After the successful modeling, bilateral ＂Fenglong＂ （丰隆 ST 40）, ＂Quchi＂ （曲池 LI 11）, and ＂Sanyinjiao＂ （三阴交 SP 6） were selected in the acupuncture group and Han＇s Acupuncture Stimulator was connected to intervent for 10 rain, once daily, for 10 successive days. Mice in the drug group were orally given Simvastatin, once daily, for 10 successive days. No intervention was given to the normal group and the model group. Serum contents of total cholesterol （TC）, triglyeeride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, malondialdehyde （MDA）, nitric oxide （NO）, endothelin （ET）, and the activity of superoxide dismutase （SOD） were detected. Results The serum contents of TG, TC and LDL-C in the model group detected on the 15th day were all higher than those of the normal group [（1.31±0.32） mmol/L vs （0.70±0.21） retool/L, （5.72±0.85） mmol/L vs （3.08±0.74） retool/L, （2.68±0.55） mmol/L vs （1.83±0.36） retool/L, respectively]. The serum content of HDL-C in the model group was lower than that in the normal group [（0.60±0.26） mmol/L vs （0.94±0.30） mmol/L], showing successful modeling. On the lOth day of successful modeling, the serum contents of MDA and ET in the acupuncture group were lower than those in the model group [（21.58±3.54） p, mol/mL vs （29.94±2.79） p, mol/mL, （44.51±5.23） pg/mL vs （67.07±11.98） pg/mL]. The serum SOD activities and NO content in the acupuncture group were higher than those in the model gropu [（264.57±14.46） U/mL vs （222.66±25.48） U/mL, （85.02±10.06） μmol/L vs （63.83±9.19） μmol/L]. Conclusion Acupuncture could lower serum contents of MDA and ET, improve SOD activities and NO content, showing acupuncture could fight against lipid peroxidation, clear free radicals, regulate as well as ameliorate the metabolic balance of free radicals, and protect the vascular endothelium in hyperlipidemia mice.
基金The National Natural Science Foundation of China(Grant No.21302079)the Fundamental Research Funds for the Central Universities(Grant No.lzujbky-2014-151)
文摘Hybrid antioxidants cinnamoyldopamine（2a）, p-coumaroyldopamine（2b）, caffeoyldopamine（2c）, feruloyldopamine（2d） and sinapoyldopamine（2e） were synthesized by conjugation of dopamine（DA） and hydroxycinnamic acids（HCAs）. The stabilities were studied in buffers at p H 1.3, p H 5.0, and p H 7.4 including the human plasma. All the compounds were found highly stable at acidic p H, but underwent hydrolysis at neutral p H. Furthermore, the hydrolysis proceeded much faster in plasma in the following order as indicated by half-life values（t1/2）, 2c（1.21 h）〈2e（1.52 h）〈2d（1.85 h）〈2b（3.38 h）〈2a（3.88 h）, correlating with the number of electron-donating groups. It has been proven by UV spectrum that 2c, 2d, and 2e displayed red shift of more than 50 nm as compared to 2a and 2b, because of the presence of OH and OCH3 groups. In addition, the compounds（2b–e） showed no cytotoxicity on normal HUVEC cells as DA, although 2a displayed a 16% inhibition of proliferation at 40 μM following 48 h incubation. Their free radical-scavenging activities were evaluated using ABTS^＊＋ and superoxide anion assays and the mechanisms were proposed. It was found that they all exhibited higher activities than trolox, a recognized antioxidant. Amazingly, in the case of the hybrids（2a–e）, their activity was higher than that of HCAs while lower or comparable to that of DA, suggesting that there may be a ＂saturation effect＂ with the hybrid molecules in the antioxidant activities.
基金Supported by The Hebei Province TCM Administra on Bureau Founda on for Tackling Key Problems of Science and Technology: 2009058
文摘Objective To observe therapeutic effects of acupuncture on the mouse of hyperlipemia and to explore the mechanisms. Methods One hundred and twenty Kunming mice, male, sanitary degree, were randomly divided into normal group （n=40）, a model group （n=40）, an acupuncture group （n=20） and a medicine group （n=20）. Except the normal group, the mice were fed with high fat forage to prepare mouse hyperlipemia model. On the 15th day of modeling, serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein-cholesterol （LDL-C）, high density lipoprotein-cholesterol （HDL-C） levels were detected in 20 normal mice and 20 model mice; electroacupuncture was given at bilateral ＂Fēnglóng＂ （丰隆 ST 40）, ＂Qūchí＂ （曲池 LI 11）, ＂Sānyīnjiāo＂ （三阴交 SP 6） in the acupuncture group, once a day, for 10 consecutive days; in the medicine group, the mice were intragastrically administrated with Simvastatin, once daily , for 10 consecutive days. After the end of treatment, serum TC, TG, LDL-C, HDL-C, malondialdehyde （MDA）, nitric oxide （NO） and endothelin （ET） contents and superoxide dismutase （SOD） activities were detected in the groups. Results On the 15th day of modeling, in the model group serum TG, TC, LDL-C contents were significantly higher （all P〈0.05） and HDL-C content was significantly lower （P〈0.01） than those in the normal group. After treatment for 10 days, in the acupuncture group and the medicine group serum TG, TC, LDL-C, MDA and ET contents were significantly lower and serum HDL-C and NO contents and SOD activities were significantly higher than those in the model group （P〈0.05, P〈0.01）, and the improving action in the acupuncture group was better than that in the medicine group （P〈0.05, P〈0.01）. Conclusion Acupuncture can regulate fat metabolism, resist lipid peroxidation and protect vascular endothelial function in the mouse of hyperlipemia.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY18H300002)the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2019RC061/2019312897)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(Nos.Y4110212 and LY19H090001)partly by the National Natural Science Foundation of China(Nos.81372301 and 81301113)
文摘Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H2O2 stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O2·- levels and construct an O2^·- reaction network. To elucidate the consequences of increased O2^·- input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca2+ levels, mitochondrial Ca^2+ uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H·-2 O2 induced a rapid increase in cellular O2 levels(>27 vs.>406 amol in 20 min), leading to increased cellular oxidizing power(evaluated by ROS levels) and decreased reducing power(evaluated by glutathione(GSH) levels). In addition, we examined the dynamics of cytosolic Ca^2+ and mitochondrial Ca^2+ by confocal laser scanning microscopy and confirmed that Ca^2+ stores in the endoplasmic reticulum were the primary source of H2O2-induced cytosolic Ca^2+ bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca^2+ signals between organelles,ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.
