In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by...In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo.3,4-Dihydroxybenzaldehyde(0.01,0.1,and 1 mg/m L)improved sperm survival rate and sperm membrane integrity in separated mouse sperm(all P<0.05).In cyclophosphamide-treated male mice(60 mg/kg/d through intraperitoneal injection for 5 d),3,4-dihydroxybenzaldehyde(40 mg/kg/d through intragastric gavage for 35 d)increased the testis index,epididymis index,and sperm nuclear maturity(all P<0.05).3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells,numbers of sperm in the lumen,normal mesenchymal cells,and close and tidy arrangement of the seminiferous tubules.3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression.In addition,it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1,PEDF,VEGF,and PPARγ.These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo.3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.展开更多
Objective:To investigate the anti-senescence effect of 3-bromo-4,5-dihydroxybenzaldehyde(BDB)from Polysiphonia morrowii Harvey in human dermal fibroblasts(HDF).Methods:HDF were subjected to treatment of BDB and then t...Objective:To investigate the anti-senescence effect of 3-bromo-4,5-dihydroxybenzaldehyde(BDB)from Polysiphonia morrowii Harvey in human dermal fibroblasts(HDF).Methods:HDF were subjected to treatment of BDB and then treated with hydrogen peroxide(H2O2)to induce premature senescence.Senescence-associatedβ-galactosidase(SA-β-gal)activity in HDF was determined using the SA-β-gal staining method.Intracellular reactive oxygen species(ROS)production was measured using the 2’,7’-dichlorodihydrofluorescein diacetate assay.Western blotting assay was performed to assess the level of antioxidant enzyme glutathione peroxidase 1(GPX1).In addition,intracellular collagen and collagenase contents were analyzed using the respective ELISA kits.Elastase activity in HDF supernatants was measured from p-nitroaniline release and normalized using total protein content.Results:Treatment of HDF with H2O2 increased the activity of SA-β-gal,but BDB pre-treatment resulted in the reduction of SA-β-gal activity.Moreover,BDB significantly reduced H2O2-induced intracellular ROS production.BDB also markedly increased the level of GPX1,which was inhibited by 400μM of H2O2.Furthermore,in in vitro study,BDB significantly increased intracellular collagen content and decreased matrix metalloproteinase-1 and elastase activities in HDF.Conclusions:Our results demonstrate that BDB shows antisenescence and anti-wrinkle activities in vitro.展开更多
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
基金Science and Technology Program of the Beijing Municipal Education Commission(Grant No.KM201810025002)National Natural Science Foundation of China(Grant No.81801522)Natural Science Foundation of Hebei Province(Grant No.H2018209342)。
文摘In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo.3,4-Dihydroxybenzaldehyde(0.01,0.1,and 1 mg/m L)improved sperm survival rate and sperm membrane integrity in separated mouse sperm(all P<0.05).In cyclophosphamide-treated male mice(60 mg/kg/d through intraperitoneal injection for 5 d),3,4-dihydroxybenzaldehyde(40 mg/kg/d through intragastric gavage for 35 d)increased the testis index,epididymis index,and sperm nuclear maturity(all P<0.05).3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells,numbers of sperm in the lumen,normal mesenchymal cells,and close and tidy arrangement of the seminiferous tubules.3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression.In addition,it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1,PEDF,VEGF,and PPARγ.These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo.3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.
基金supported by Korea Basic Science Institute(grant number C39260)National Research Foundation of Korea(NRF)funded by the Korea government(MSIT)(grant number NRF-2019R1C1C1005608)a research grant from the Korea Institute of Ocean Science and Technology(PE99822)
文摘Objective:To investigate the anti-senescence effect of 3-bromo-4,5-dihydroxybenzaldehyde(BDB)from Polysiphonia morrowii Harvey in human dermal fibroblasts(HDF).Methods:HDF were subjected to treatment of BDB and then treated with hydrogen peroxide(H2O2)to induce premature senescence.Senescence-associatedβ-galactosidase(SA-β-gal)activity in HDF was determined using the SA-β-gal staining method.Intracellular reactive oxygen species(ROS)production was measured using the 2’,7’-dichlorodihydrofluorescein diacetate assay.Western blotting assay was performed to assess the level of antioxidant enzyme glutathione peroxidase 1(GPX1).In addition,intracellular collagen and collagenase contents were analyzed using the respective ELISA kits.Elastase activity in HDF supernatants was measured from p-nitroaniline release and normalized using total protein content.Results:Treatment of HDF with H2O2 increased the activity of SA-β-gal,but BDB pre-treatment resulted in the reduction of SA-β-gal activity.Moreover,BDB significantly reduced H2O2-induced intracellular ROS production.BDB also markedly increased the level of GPX1,which was inhibited by 400μM of H2O2.Furthermore,in in vitro study,BDB significantly increased intracellular collagen content and decreased matrix metalloproteinase-1 and elastase activities in HDF.Conclusions:Our results demonstrate that BDB shows antisenescence and anti-wrinkle activities in vitro.
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
