For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human...For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.展开更多
Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage： no...Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage： normal saline solution （control）; arsenic trioxide （ATO; 4 mg/kg）; GSPE （400 mg/kg）; ATO＋GSPE （100 mg/kg）; ATO＋GSPE （200 mg/kg） and ATO＋GSPE （400 mg/kg）. Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor （erythroid-derived 2）-like 2 （Nrf2）, heme oxygenase 1 （HO1）, glutathione S-transferase （GST）, NAD（P）H dehydrogenase, and quinone 1 [NQO1） expression in the testis was detected by real-time PCR. Superoxide dismutase （SOD）, glutathione （GSH）, total antioxidative capability （T-AOC）, malondialdehyde （MDA）, 8-hydroxydeoxyguanosine （8-OHdG）, and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO ＋GSPE group showed recovery of the measured parameters. Mice treated with ATO＋high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.展开更多
This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided ra...This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups:control group,model group,three GSPE groups(low dose,medium dose and high dose).Control group received subcutaneous injection of physiological saline.Model group was given subcutaneous injection of sodium selenite(20 μmol/kg body weight) on the postpartum day 10,and once every other day for consecutive three times thereafter.GSPE treated groups were respectively administered GSPE at doses of 50,100,and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection(that was,on the postpartum day 8),and once daily for fourteen consecutive days thereafter.The opacity of lenses was observed,graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured.The lenses were analyzed for superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),calcium(Ca 2+),nitric oxide(NO) and anti-hydroxyl radical ability(anti-OH).The histomorphology of lenses was observed with HE staining under a light microscope.The levels of calpainⅡ,and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR.The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group,and the achievement ratio of model group was 100%.As compared with model group,the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups.Moreover,we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes(SOD,CAT,GSH-PX) and anti-OH ability,accompanied by a significant increase in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.Administration of GSPE could dose-dependently preserve the activities of these antioxidative enzymes and anti-OH ability,accompanied by a significant reduction in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.These results suggested that GSPE markedly prevented selenite-induced cataract formation probably by suppressing the generation of lipid peroxidation and free radicals as well as the activation of iNOS,and calpainⅡ in the lenses.展开更多
Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury ...Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.展开更多
Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer’s disease(AD).Currently,there is no effective drug available for the treatment of AD.Previous studies have demonstrat...Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer’s disease(AD).Currently,there is no effective drug available for the treatment of AD.Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation.Grape seed proanthocyanidin extract(GSPE)has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage.This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)(ICV-STZ).Rats were treated with GSPE(50,100,or 200 mg/kg every day)by intragastrical(ig.)administration for continuous 7 weeks,and ICV-STZ(3 mg/kg)was performed on the first day and third day of week 5.Learning and memory abilities were assessed by the Morris water maze(MWM)test at week 8.After behavioral test,hippocampal long-term potentiation(LTP)was recorded,and the levels of malondialdehyde(MDA),superoxide dismutases(SOD),glutathione(GSH)and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats.Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats,significantly increased the levels of MDA,and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex.In contrast,GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ,decreased the level of MDA,and increased the level of SOD and GSH.Furthermore,Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ.Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities.Therefore,GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD.展开更多
AIM: To explore the effect of grape seed proanthocyanidin(GSP) in liver ischemia/reperfusion(IR) injury and alleviation of endoplasmic reticulum stress.METHODS: Male Sprague-Dawley rats(220-250 g) were divided into th...AIM: To explore the effect of grape seed proanthocyanidin(GSP) in liver ischemia/reperfusion(IR) injury and alleviation of endoplasmic reticulum stress.METHODS: Male Sprague-Dawley rats(220-250 g) were divided into three groups, namely, sham, IR, and GSP groups(n = 8 each). A liver IR(70%) model was established and reperfused for 6 h. Prior to reperfusion, the GSP group was administered with GSP(100 mg/kg) for 15 d, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase and methane dicarboxylic aldehyde were detected. Western blot was conducted to analyze the expression of glucoseregulated protein 78, CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb. Apoptotic cells were detected by TUNEL staining.RESULTS: The serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the IR group(P s < 0.05). The methanedicarboxylic aldehyde level was decreased in the GSP group, but the superoxide dismutase level was reversed(P s < 0.05). Similarly, GSP downregulated the proinflammatory factors and upregulated the levels of anti-inflammatory factors(Ps < 0.05). Western blot data showed that GSP increased glucose-regulated protein 78 expression and suppressed expression of CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb compared with the IR group.CONCLUSION: GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving endoplasmic reticulum stress through regulation of related signaling pathways to protect the liver against IR injury.展开更多
文摘For years,a great deal of work has been carried out on proanthocyanidins extracted from various kinds of plants,of which grape seed proanthocyanidins(GSPs)attract most attention due to their benefi cial roles in human health.Indeed,GSPs have demonstrated substantial health benefi ts for a variety of disorders such as cancer,atherosclerosis,and cardiovascular diseases,to just name a few.In particular,GSPs inhibit cell proliferation,migration and invasion,and induce apoptosis and cell cycle arrest in various human cancers,including head and neck carcinoma,gastrointestinal tumors,lung cancer,skin tumors,and reproductive tumors,which points them to be promising chemo-preventive and/or chemotherapeutic agents.In this setting,we summarized the eff ects of GSPs against various types of cancer with a focus on the detailed molecular mechanisms involving various signaling pathways of tumor cells,which may serve as a basis for development of improved chemo-preventive or therapeutic strategies for cancer.
基金supported by a grant from the Xinjiang Production and Construction Corps(2014BA039)Shihezi University grant(RCZX201112)
文摘Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage： normal saline solution （control）; arsenic trioxide （ATO; 4 mg/kg）; GSPE （400 mg/kg）; ATO＋GSPE （100 mg/kg）; ATO＋GSPE （200 mg/kg） and ATO＋GSPE （400 mg/kg）. Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor （erythroid-derived 2）-like 2 （Nrf2）, heme oxygenase 1 （HO1）, glutathione S-transferase （GST）, NAD（P）H dehydrogenase, and quinone 1 [NQO1） expression in the testis was detected by real-time PCR. Superoxide dismutase （SOD）, glutathione （GSH）, total antioxidative capability （T-AOC）, malondialdehyde （MDA）, 8-hydroxydeoxyguanosine （8-OHdG）, and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO ＋GSPE group showed recovery of the measured parameters. Mice treated with ATO＋high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.
文摘This study investigated the inhibitory effect of grape seed proanthocyanidin extract(GSPE) on selenite-induced cataract formation in rats and the possible mechanism.Eighty 8-day-old Sprague-Dawley rats were divided randomly into 5 groups:control group,model group,three GSPE groups(low dose,medium dose and high dose).Control group received subcutaneous injection of physiological saline.Model group was given subcutaneous injection of sodium selenite(20 μmol/kg body weight) on the postpartum day 10,and once every other day for consecutive three times thereafter.GSPE treated groups were respectively administered GSPE at doses of 50,100,and 200 mg/kg body weight intragastrically 2 days prior to the selenite injection(that was,on the postpartum day 8),and once daily for fourteen consecutive days thereafter.The opacity of lenses was observed,graded and photographed under the slit lamp microscopy and the maximal diameter of the nuclear cataract plaques was measured.The lenses were analyzed for superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),calcium(Ca 2+),nitric oxide(NO) and anti-hydroxyl radical ability(anti-OH).The histomorphology of lenses was observed with HE staining under a light microscope.The levels of calpainⅡ,and iNOS protein and mRNA expression in lenses were detected by using immunohistochemistry and real-time quantitative RT-PCR.The results showed subcutaneous injection of sodium selenite led to severe nuclear cataract in model group,and the achievement ratio of model group was 100%.As compared with model group,the degree of lenses opacity and the maximal diameter of nuclear cataract plaques were significantly reduced in GSPE-treated groups.Moreover,we observed selenite treatment caused a significant decrease in the activities of antioxidative enzymes(SOD,CAT,GSH-PX) and anti-OH ability,accompanied by a significant increase in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.Administration of GSPE could dose-dependently preserve the activities of these antioxidative enzymes and anti-OH ability,accompanied by a significant reduction in the levels of MDA,NO,Ca 2+ as well as iNOS,and calpainⅡ protein and mRNA expression.These results suggested that GSPE markedly prevented selenite-induced cataract formation probably by suppressing the generation of lipid peroxidation and free radicals as well as the activation of iNOS,and calpainⅡ in the lenses.
基金Supported by the National Natural Science Foundation of China(Nos.30700884,30873145)the Distinguished Middle-aged and Young Scientist Encourage and Reward Foundation of Shandong Province,China(No.BS2009SW015)
文摘Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
基金This work was supported by grants from the Scientific Research Projects of the Education Department of Hubei of China(No.D20162801)Open Fund Project of Hubei Key Laboratory of Cardiovascular,Cerebrovascularand Metabolic Disorders(No.2019-20XZ06).
文摘Progressive memory loss and cognitive impairment are the main clinical manifestations of Alzheimer’s disease(AD).Currently,there is no effective drug available for the treatment of AD.Previous studies have demonstrated that the cognitive impairment of AD is associated with oxidative stress and the inhibition of AKT and ERK phosphorylation.Grape seed proanthocyanidin extract(GSPE)has been shown to have strong antioxidant effect and can protect the nervous system from oxidative stress damage.This study aimed to investigate the protective effect of GSPE on the cognitive and synaptic impairments of AD using a sporadic AD rat model induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)(ICV-STZ).Rats were treated with GSPE(50,100,or 200 mg/kg every day)by intragastrical(ig.)administration for continuous 7 weeks,and ICV-STZ(3 mg/kg)was performed on the first day and third day of week 5.Learning and memory abilities were assessed by the Morris water maze(MWM)test at week 8.After behavioral test,hippocampal long-term potentiation(LTP)was recorded,and the levels of malondialdehyde(MDA),superoxide dismutases(SOD),glutathione(GSH)and the protein expression of AKT and ERK were measured in the hippocampus and cerebral cortex of rats.Our study revealed that ICV-STZ significantly impaired the working learning ability and hippocampal LTP of rats,significantly increased the levels of MDA,and decreased the activity of SOD and GSH in the hippocampus and cerebral cortex.In contrast,GSPE treatment prevented the impairment of cognitive function and hippocampal LTP induced by ICV-STZ,decreased the level of MDA,and increased the level of SOD and GSH.Furthermore,Western blot results showed that GSPE treatment could prevent the loss of AKT and ERK activities in the hippocampus and cerebral cortex induced by ICV-STZ.Our findings demonstrate that GSPE treatment could ameliorate the impairment of cognitive ability and hippocampal synaptic plasticity in a rat model of sporadic AD by inhibiting oxidative stress and preserving AKT and ERK activities.Therefore,GSPE may be an effective agent for the treatment of cognitive deficits associated with sporadic AD.
基金Supported by The Jiangsu Province Natural Science Fund Subject,No.BK20131445the Scientific Research Program of Ministry of Health,No.201302009
文摘AIM: To explore the effect of grape seed proanthocyanidin(GSP) in liver ischemia/reperfusion(IR) injury and alleviation of endoplasmic reticulum stress.METHODS: Male Sprague-Dawley rats(220-250 g) were divided into three groups, namely, sham, IR, and GSP groups(n = 8 each). A liver IR(70%) model was established and reperfused for 6 h. Prior to reperfusion, the GSP group was administered with GSP(100 mg/kg) for 15 d, and liver histology was then investigated. Serum aminotransferase and inflammatory mediators coupled with superoxide dismutase and methane dicarboxylic aldehyde were detected. Western blot was conducted to analyze the expression of glucoseregulated protein 78, CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb. Apoptotic cells were detected by TUNEL staining.RESULTS: The serum aminotransferase, apoptotic cells, and Suzuki scores decreased in the GSP group compared with the IR group(P s < 0.05). The methanedicarboxylic aldehyde level was decreased in the GSP group, but the superoxide dismutase level was reversed(P s < 0.05). Similarly, GSP downregulated the proinflammatory factors and upregulated the levels of anti-inflammatory factors(Ps < 0.05). Western blot data showed that GSP increased glucose-regulated protein 78 expression and suppressed expression of CCAAT/enhancer-binding protein homologous protein, activating transcription factor-4, inositol-requiring enzyme-1, procaspase-12, and nuclear factor-κb compared with the IR group.CONCLUSION: GSP possesses antioxidative, anti-inflammatory, and antiapoptotic effects by relieving endoplasmic reticulum stress through regulation of related signaling pathways to protect the liver against IR injury.
