BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM T...BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.展开更多
Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editor...Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editorial,we review and comment on an article by Wang et al published in 2024.This study aimed to evaluate the potential therapeutic benefits of ginsenoside Rg1 in AA,focusing on its protective effects and uncovering the underlying mechanisms.Cyclophosphamide(CTX)administration caused substantial damage to the structural integrity of the bone marrow and decreased the number of hematopoietic stem cells,thereby establishing an AA model.Compared with the AA group,ginsenoside Rg1 alleviated the effects of CTX by reducing apoptosis and inflammatory factors.Mechanistically,treatment with ginsenoside Rg1 significantly mitigated myelosuppression in mice by inhibiting the mitogen activated protein kinase signaling pathway.Thus,this study indicates that ginsenoside Rg1 could be effective in treating AA by reducing myelosuppression,primarily through its influence on the mitogen activated protein kinase signaling pathway.We expect that our review and comments will provide valuable insights for the scientific community related to this research and enhance the overall clarity of this article.展开更多
OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS T...OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS The anti-I/R effect of Rg1 were investigated in vitro and in vivo,and the dynamics of nuclear accumulation and the transcriptional activity of NF-E2-related factor 2(Nrf2) determined by Western blotting and Dual Luciferase Reporter Assay,respectively.Nrf2 siRNA was employed to investigate Nrf2′s role in the protective effect of Rg1 against I/R.Furthermore,the role of miR-144,which could regulate post-translational Nrf2 levels,was investigated in the anti-I/R effect of Rg1 by injection of AAV-hypoxia-inducible factor miR-144-shRNA in the predicted ischemic penumbra.RESULTS It was found that the anti-I/R effect of Rg1 was related to its anti-oxidative capacity,which is mainly regulated by the Nrf2/antioxidant response element(ARE) pathway.Further study suggested that Rg1 contributes to the enhancement of the Nrf2/ARE pathway,as manifested by increasing the dynamic peak content of Nrf2,which prolonged the maintenance stage,and promoting the expression of ARE-target genes after oxygen glucose deprivation/reperfusion(OGD/R) in PC12 cells.Nrf2-siRNA application significantly reduced these changes.Furthermore,the enhancement of the Nrf2/ARE pathway by Rg1 was independent of disassociation from Keap1;rather it was a result of posttranslational regulations.It was found that Rg1 significantly reduced the expression of miR-144,which down-regulates Nrf2 production by targeting its 3′-untranslated region,after OGD/R.Knockdown of Nrf2 showed no effect on the expression of miR-144,indicating that miR-144 is an upstream regulator of Nrf2.Moreover,direct binding between Nrf2 and miR-144 in the PC12 cells was identified.Application of anti-miR-144 significantly reduced Rg1′s anti-OGD/R capacity.Final y,the role of miR-144 in Rg1′ s anti-I/R effect was tested by inhibiting miR-144 in the predicted ischemic penumbra when hypoxia-inducible-factor was activated.The results showed that loss of miR-144 abolished the anti-I/R effect of Rg1,which included reduced infarct volume,improved neurological scores,attenuated oxidative impairment,as well as activation of the Nrf2/ARE pathway.CONCLUSION Oxidative stress after I/R is alleviated by Rg1 through inhibition of miR-144 activity and subsequent promotion of the Nrf2/ARE pathway at the post-translational level.展开更多
Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were di...Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.展开更多
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
文摘Aplastic anemia(AA)is a rare but serious condition in which the bone marrow fails to produce sufficient new blood cells,leading to fatigue,increased susceptibility to infection,and uncontrolled bleeding.In this editorial,we review and comment on an article by Wang et al published in 2024.This study aimed to evaluate the potential therapeutic benefits of ginsenoside Rg1 in AA,focusing on its protective effects and uncovering the underlying mechanisms.Cyclophosphamide(CTX)administration caused substantial damage to the structural integrity of the bone marrow and decreased the number of hematopoietic stem cells,thereby establishing an AA model.Compared with the AA group,ginsenoside Rg1 alleviated the effects of CTX by reducing apoptosis and inflammatory factors.Mechanistically,treatment with ginsenoside Rg1 significantly mitigated myelosuppression in mice by inhibiting the mitogen activated protein kinase signaling pathway.Thus,this study indicates that ginsenoside Rg1 could be effective in treating AA by reducing myelosuppression,primarily through its influence on the mitogen activated protein kinase signaling pathway.We expect that our review and comments will provide valuable insights for the scientific community related to this research and enhance the overall clarity of this article.
基金The project supported by National Natural Science Foundation of China(81603315 81730096+4 种基金 81373551 81730093U1402221)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004)the Opening Program of Shanxi Key Laboratory of Chinese Medicine Encephalopathy(CME-OP-2017001)
文摘OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS The anti-I/R effect of Rg1 were investigated in vitro and in vivo,and the dynamics of nuclear accumulation and the transcriptional activity of NF-E2-related factor 2(Nrf2) determined by Western blotting and Dual Luciferase Reporter Assay,respectively.Nrf2 siRNA was employed to investigate Nrf2′s role in the protective effect of Rg1 against I/R.Furthermore,the role of miR-144,which could regulate post-translational Nrf2 levels,was investigated in the anti-I/R effect of Rg1 by injection of AAV-hypoxia-inducible factor miR-144-shRNA in the predicted ischemic penumbra.RESULTS It was found that the anti-I/R effect of Rg1 was related to its anti-oxidative capacity,which is mainly regulated by the Nrf2/antioxidant response element(ARE) pathway.Further study suggested that Rg1 contributes to the enhancement of the Nrf2/ARE pathway,as manifested by increasing the dynamic peak content of Nrf2,which prolonged the maintenance stage,and promoting the expression of ARE-target genes after oxygen glucose deprivation/reperfusion(OGD/R) in PC12 cells.Nrf2-siRNA application significantly reduced these changes.Furthermore,the enhancement of the Nrf2/ARE pathway by Rg1 was independent of disassociation from Keap1;rather it was a result of posttranslational regulations.It was found that Rg1 significantly reduced the expression of miR-144,which down-regulates Nrf2 production by targeting its 3′-untranslated region,after OGD/R.Knockdown of Nrf2 showed no effect on the expression of miR-144,indicating that miR-144 is an upstream regulator of Nrf2.Moreover,direct binding between Nrf2 and miR-144 in the PC12 cells was identified.Application of anti-miR-144 significantly reduced Rg1′s anti-OGD/R capacity.Final y,the role of miR-144 in Rg1′ s anti-I/R effect was tested by inhibiting miR-144 in the predicted ischemic penumbra when hypoxia-inducible-factor was activated.The results showed that loss of miR-144 abolished the anti-I/R effect of Rg1,which included reduced infarct volume,improved neurological scores,attenuated oxidative impairment,as well as activation of the Nrf2/ARE pathway.CONCLUSION Oxidative stress after I/R is alleviated by Rg1 through inhibition of miR-144 activity and subsequent promotion of the Nrf2/ARE pathway at the post-translational level.
基金funding support from the Open Funding Project of National Key Laboratory of Human Factors Engineering (No. SYFD150051808K)the National Key Research and Development Program of China (No. 2016YFE0131800)the Highend Talents Recruitments Program (Liu Xin-Min group) of Luzhou Municipal People’s Government and Development of Animal Model on Human Diseases (No. 2016-I2M-2-006)
文摘Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.
