Objective:This study aimed to systematically evaluate the effect of idebenone tablets in the treatment of post-stroke depression(Post-Stroke Depression,PSD).Methods:This study was a single-arm,prospective,observationa...Objective:This study aimed to systematically evaluate the effect of idebenone tablets in the treatment of post-stroke depression(Post-Stroke Depression,PSD).Methods:This study was a single-arm,prospective,observational study that recruited PSD patients who met the inclusion criteria after being assessed by the investigator between January 2022 and June 2023.The demographic characteristics,disease status,treatment status,and medication status of the patients were collected through questionnaires,and the Hamilton depression score of the patients was collected through the Case Report Form(CRF)to evaluate the effectiveness and safety of idebenone tablet treatment.Results:A total of 4902 PSD patients were included in this study,of which 2496 were males,accounting for 50.9%,and 2406 were females,accounting for 49.1%.According to the Hamilton Depression Rating Scale(HAMD),13.9%were no depression at the first visit,53.0%were mildly depressed,24.3%were moderately depressed,and 8.8%were severely depressed.After treatment,the proportion of no depression was 26.1%,mild depression accounted for 53.3%,moderate depression accounted for 16.8%,and severe depression accounted for 3.8%,and the difference in the proportion of depression before and after treatment was statistically significant(P<0.05).Conclusion:Idebenone tablets can significantly reduce Hamilton’s depression score,suggesting that it has a significant therapeutic effect in improving PSD symptoms.展开更多
Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-in...Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.展开更多
Background:Naohuan Dan is a prescription used to treat dementia.This study aims to assess the effectiveness and safety of Naohuan Dan combined with idebenone in treating mild cognitive impairment(MCI)with kidney defic...Background:Naohuan Dan is a prescription used to treat dementia.This study aims to assess the effectiveness and safety of Naohuan Dan combined with idebenone in treating mild cognitive impairment(MCI)with kidney deficiency and phlegm stasis.Materials and methods:This retrospective,observational clinical trial enrolled 64 MCI patients treated in the Sun Yat-sen Memorial Hospital,Zhongshan University,from May 1,2019,to April 30,2022.The 32 patients in the treatment group received Naohuan Dan combined with idebenone,whereas the 32 patients in the control group were treated with idebenone alone.The observation lasted for 12 weeks.The primary outcomes were the Mini-Mental State Examination(MMSE)score and clinical efficacy,whereas secondary outcomes included the Montreal Cognitive Assessment(MCS)score,the activities of daily living(ADL)score,the Geriatric Depression Scale(GDS)score,the traditional Chinese medicine(TCM)syndrome score,and changes in serum markers.Neuron-specific enolase(NSE),interleukin 8(IL-8),and tumor necrosis factorα(TNF-α)were taken as the serological indicators for evaluating cognitive function.Adverse events in both groups were recorded during the treatment period.Results:The treatment group demonstrated higher MMSE scores and clinical efficacy than the control group,specifically in the scores of spatial orientation,attention and calculation,and language proficiency in the MMSE scale.The treatment group outperformed the control group in MCS,ADLs,GDS,and TCM syndrome scores.Furthermore,the treatment group was superior to the control group in recovering the levels of NSE,IL-8,and TNF-α.In addition,the treatment group had lower incidence of adverse reactions such as nausea and poor appetite than the control group.Conclusions:The 12-week treatment with Naohuan Dan combined with idebenone significantly improved the cognitive function and daily life abilities,lowered the depression levels,and reduced the occurrence of adverse events among patients withMCI.These findings offer valuable insights into the efficacy of integrating TCM with Western medicine in the clinical management of MCI.展开更多
The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver functi...The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.展开更多
Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.H...Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.However,the disorder has no available cures,since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them.Herein,PARKIN mRNA-loaded nanoparticle(mNP)-engineered mitochondria(mNP-Mito)were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria,normalizing the function of complex I for treating LHON.The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer,along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process.In a mouse model induced with a complex I inhibitor(rotenone,Rot),mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity(76.5%)compared to the group exposed to Rot damage(29.5%),which greatly promoted the restoration of ATP generation and mitiga-tion of ocular mitochondrial disease-related phenotypes.This study highlights the significance of nanoen-gineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.展开更多
文摘Objective:This study aimed to systematically evaluate the effect of idebenone tablets in the treatment of post-stroke depression(Post-Stroke Depression,PSD).Methods:This study was a single-arm,prospective,observational study that recruited PSD patients who met the inclusion criteria after being assessed by the investigator between January 2022 and June 2023.The demographic characteristics,disease status,treatment status,and medication status of the patients were collected through questionnaires,and the Hamilton depression score of the patients was collected through the Case Report Form(CRF)to evaluate the effectiveness and safety of idebenone tablet treatment.Results:A total of 4902 PSD patients were included in this study,of which 2496 were males,accounting for 50.9%,and 2406 were females,accounting for 49.1%.According to the Hamilton Depression Rating Scale(HAMD),13.9%were no depression at the first visit,53.0%were mildly depressed,24.3%were moderately depressed,and 8.8%were severely depressed.After treatment,the proportion of no depression was 26.1%,mild depression accounted for 53.3%,moderate depression accounted for 16.8%,and severe depression accounted for 3.8%,and the difference in the proportion of depression before and after treatment was statistically significant(P<0.05).Conclusion:Idebenone tablets can significantly reduce Hamilton’s depression score,suggesting that it has a significant therapeutic effect in improving PSD symptoms.
基金supported by the following grants:the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(No.U22A20269)the National Key R&D Program of China(No.2018YFC1311300)the National Natural Science Foundation of China(Nos.82200262 and 82000229).
文摘Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.
基金This work was supported by the Natural Science Foundation of Guangdong,China(2019A1515011414 and 2023A1515011136)the Traditional Chinese Medicine Bureau of Guangdong Province,China(20211072).
文摘Background:Naohuan Dan is a prescription used to treat dementia.This study aims to assess the effectiveness and safety of Naohuan Dan combined with idebenone in treating mild cognitive impairment(MCI)with kidney deficiency and phlegm stasis.Materials and methods:This retrospective,observational clinical trial enrolled 64 MCI patients treated in the Sun Yat-sen Memorial Hospital,Zhongshan University,from May 1,2019,to April 30,2022.The 32 patients in the treatment group received Naohuan Dan combined with idebenone,whereas the 32 patients in the control group were treated with idebenone alone.The observation lasted for 12 weeks.The primary outcomes were the Mini-Mental State Examination(MMSE)score and clinical efficacy,whereas secondary outcomes included the Montreal Cognitive Assessment(MCS)score,the activities of daily living(ADL)score,the Geriatric Depression Scale(GDS)score,the traditional Chinese medicine(TCM)syndrome score,and changes in serum markers.Neuron-specific enolase(NSE),interleukin 8(IL-8),and tumor necrosis factorα(TNF-α)were taken as the serological indicators for evaluating cognitive function.Adverse events in both groups were recorded during the treatment period.Results:The treatment group demonstrated higher MMSE scores and clinical efficacy than the control group,specifically in the scores of spatial orientation,attention and calculation,and language proficiency in the MMSE scale.The treatment group outperformed the control group in MCS,ADLs,GDS,and TCM syndrome scores.Furthermore,the treatment group was superior to the control group in recovering the levels of NSE,IL-8,and TNF-α.In addition,the treatment group had lower incidence of adverse reactions such as nausea and poor appetite than the control group.Conclusions:The 12-week treatment with Naohuan Dan combined with idebenone significantly improved the cognitive function and daily life abilities,lowered the depression levels,and reduced the occurrence of adverse events among patients withMCI.These findings offer valuable insights into the efficacy of integrating TCM with Western medicine in the clinical management of MCI.
文摘The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.
基金supported by the National Natural Science Foundation of China(82020108029,82304416,82073398,82302367,China)supported by the Natural Science Foundation of Jiangsu Province(BK20231016,BK20231019,China)+5 种基金the China Postdoctoral Science Foundation(grant Number:2022M720173,China)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023,China)the Fundamental Research Funds for the Central Universities(2632023GR20,China)State Key Laboratory of Natural Medicines China Pharmaceutical University(SKLNMZZ202021,China)Double First-class University Projects(CPU2018GY06,China)Double First-Rate construction plan of China Pharmaceutical University(CPU2022QZ18,China)。
文摘Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.However,the disorder has no available cures,since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them.Herein,PARKIN mRNA-loaded nanoparticle(mNP)-engineered mitochondria(mNP-Mito)were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria,normalizing the function of complex I for treating LHON.The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer,along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process.In a mouse model induced with a complex I inhibitor(rotenone,Rot),mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity(76.5%)compared to the group exposed to Rot damage(29.5%),which greatly promoted the restoration of ATP generation and mitiga-tion of ocular mitochondrial disease-related phenotypes.This study highlights the significance of nanoen-gineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.
