Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and e...Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.展开更多
Exercise-induced fatigue represents a complex physiological response triggered by physical exertion,with its mechanisms primarily originating from central and peripheral systems.Central fatigue arises from neurotransm...Exercise-induced fatigue represents a complex physiological response triggered by physical exertion,with its mechanisms primarily originating from central and peripheral systems.Central fatigue arises from neurotransmitter imbalances such as elevated serotonin and reduced dopamine levels,leading to drowsiness and diminished motor performance.Peripheral fatigue occurs at the muscular level,where energy depletion,metabolic waste accumulation,and oxidative stress impair muscle contraction function.Astaxanthin,a potent antioxidant,directly and primarily alleviates peripheral fatigue through its antioxidant,anti-inflammatory,and mitochondrial protective effects.Simultaneously,by improving the peripheral environment and reducing the transmission of fatigue signals to the brain,it indirectly helps alleviate central fatigue.Based on this,this paper reviews the mechanisms of action and related research progress of astaxanthin on exercise-induced fatigue,and discusses its application value and challenges based on the current status.展开更多
Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to ev...Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to evaluate the antioxidant efficacy of mitochondria-targeted astaxanthin nanoparticle on hydrogen peroxideinduced oxidative damage.As expected,mitochondria-targeted nanoparticle showed excellent mitochondria co-localization ability with higher Pearson's correlation coefficient(r=0.88).In vitro experiments suggested that the mitochondria-targeted astaxanthin nanoparticle could promote cell viability and increase antioxidantrelated enzyme activities.Simultaneously,metabolomics analysis indicated that mitochondria-targeted astaxanthin nanoparticle could alleviate oxidative stress by regulating amino acid metabolism and energy metabolism.Altogether,all these results strongly confirmed the mitochondria-targeted strategy for astaxanthin delivery could relieve oxidative stress and had great promise in the application of disease intervention.展开更多
Saline treatment is a low-cost,simple,and effective method to stimulate astaxanthin accumulation in Haematococcus pluvialis,and is proposed to be applied in the second stage of a 2-stage culture since it does not nece...Saline treatment is a low-cost,simple,and effective method to stimulate astaxanthin accumulation in Haematococcus pluvialis,and is proposed to be applied in the second stage of a 2-stage culture since it does not necessitate changing the medium.To understand the effect of salinity on the astaxanthin production of H.pluvialis,the photosynthetic activity and the biocomponents production in 1-and 2-stage cultures in different salinities were investigated.Except for astaxanthin synthesis,which increased at low salinities of 2 and 5-g/L NaCl,most biocomponent yields decreased in 1-stage cultures as salinity increased.At a salinity of 5-g/L NaCl,the 2-stage culture further increased astaxanthin production to 18.41±0.24 mg/L,which was more than 2.0 times that of the control.Saline treatment led to an overall decrease in photosynthetic performance indices of H.pluvialis,and had an impact on five sites of the electron transport chain:the energy connection between antenna and reaction center of photosystemⅡ(PSⅡ),oxygen evolving complex activity on the donor side,the electron transfer from plastoquinone A(Q_(A))to plastoquinone B(Q_(B))and from plastoquinone(PQ)to receptor side of photosystem I(PS I),and the pool size of the end electron acceptors in PSⅠacceptor side.The excitation imbalance between PSⅠand PSⅡcaused by the variance in the electron transfer chain necessitated the synthesis of antioxidants like astaxanthin in order to ensure cell viability.The accumulation of astaxanthin was found to be closely correlated with the stabilized or enhanced the maximum relative electron transfer rate(rETR_(max))and the PSⅡactual quantum yield(QY_(SS))as well as the increased fluorescence yield at J-step(V_(J)).This work offers the novel insight of how saline stress controls H.pluvialis photosynthetic activity and astaxanthin synthesis.展开更多
Autophagy directly regulates the amyloid beta-peptide(Aβ)clearance,and its dysfunction occurs in the early pathogenesis of Alzheimer's disease(AD).We previously reported that docosahexaenoic acid-acylated astaxan...Autophagy directly regulates the amyloid beta-peptide(Aβ)clearance,and its dysfunction occurs in the early pathogenesis of Alzheimer's disease(AD).We previously reported that docosahexaenoic acid-acylated astaxanthin monoester(AST-DHA)showed neuroprotection against AD pathology.However,its in-depth mechanism and autophagic responses in AD brains are poorly understood.Herein,SH-SY5Y cells overexpressing the Swedish mutation(K595N/M596L)of APP gene were established to preliminarily evaluate the actions of AST-DHA on reducing Aβ_(1-42)levels and regulating autophagy.In microglial BV2 cells,AST-DHA and free astaxanthin(F-AST)recovered p62 and LC3Ⅱ/Ⅰlevels,and restored autophagy flux by rescuing the late phase of microglial autophagy.Notably,autophagic inhibitor bafilomycin A1 blunted the abilities of AST-DHA to reduce Aβ_(1-42)and fibral Aβ,suggesting that AST-DHA probably promoted Aβclearance in a microglial autophagy-dependent manner.Further studies in APP/PS1 mice verified that dietary AST-DHA and F-AST promoted Aβphagocytosis via microglial autophagy.Significant decreases of Iba1 and p62 were observed around Aβplaque in the hippocampus and cortex using triple fluorescence staining.Furthermore,AST-DHA exhibited superior performance over F-AST in restoring autophagic dysfunction,ameliorating Aβburden and cognitive deficit.Our findings suggest a possible mechanism of AST-DHA in improving AD by which it restores microglial autophagy to facilitate cerebral Aβclearance.It supports the future application of AST-DHA as an autophagic regulator in maintaining brain function.展开更多
Astaxanthin(AX)and vitamin E(VE)are widely consumed nutritional supplements in China,with its beneficial effects predominantly attributed to all-trans AX and VE.The aim of this study is to develop and validate a rapid...Astaxanthin(AX)and vitamin E(VE)are widely consumed nutritional supplements in China,with its beneficial effects predominantly attributed to all-trans AX and VE.The aim of this study is to develop and validate a rapid and accurate method for quantifying the content of AX and VE in nutritional supplement products using highly sensitive1H NMR method.Coumarin was chosen as the internal standard.Specific signals from AX was optimal at H-7,7'in the chemical shift range ofδ6.17–6.24 ppm,whereas the signals of VE atδ2.59 ppm.To demonstrate the reliability of this analytical approach the proposed method underwent rigorous validation,specificity,limit of detection(LOD),limit of quantitation(LOQ),linearity,accuracy,precision,and recovery.The accuracy of the validation method was 3.10%for AX and 1.99%for VE.The results indicated that the method was precise and reliable.The method has been successfully applied to simultaneous quantification of AX and VE in nutritional supplements products.展开更多
The cardiovascular diseases(CVD)continue to be the major threat to global public health over the years,while one of the effective methods to treat CVD is stent intervention.Biomedical magnesium(Mg)alloys have great po...The cardiovascular diseases(CVD)continue to be the major threat to global public health over the years,while one of the effective methods to treat CVD is stent intervention.Biomedical magnesium(Mg)alloys have great potential applications in cardiovascular stents benefit from their excellent biodegradability and absorbability.However,excessive degradation rate and the delayed surface endothelialization still limit their further application.In this study,we modified a Mg-Zn-Y-Nd alloy(ZE21B)by preparing MgF_(2) as the corrosion resistance layer,the dopamine polymer film(PDA)as the bonding layer,and hyaluronic acid(HA)loaded astaxanthin(ASTA)as an important layer to directing the cardiovascular cells fate.The electrochemical test results showed that the MgF_(2)/PDA/HA-ASTA coating improved the corrosion resistance of ZE21B.The cytocompatibility experiments also demonstrated that this novel composite coating also selectively promoted endothelial cells proliferation,inhibited hyperproliferation of smooth muscle cells and adhesion of macrophages.Compared with the HAloaded rapamycin(RAPA)coating,our MgF_(2)/PDA/HA-ASTA coating showed better blood compatibility and cytocompatibility,indicating stronger multi-functions for the ZE21B alloy on cardiovascular application.展开更多
基金supported by grants from the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,JYY2023-6)the R&D Program of Beijing Municipal Education Commission(KZ20231002543).
文摘Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.
文摘Exercise-induced fatigue represents a complex physiological response triggered by physical exertion,with its mechanisms primarily originating from central and peripheral systems.Central fatigue arises from neurotransmitter imbalances such as elevated serotonin and reduced dopamine levels,leading to drowsiness and diminished motor performance.Peripheral fatigue occurs at the muscular level,where energy depletion,metabolic waste accumulation,and oxidative stress impair muscle contraction function.Astaxanthin,a potent antioxidant,directly and primarily alleviates peripheral fatigue through its antioxidant,anti-inflammatory,and mitochondrial protective effects.Simultaneously,by improving the peripheral environment and reducing the transmission of fatigue signals to the brain,it indirectly helps alleviate central fatigue.Based on this,this paper reviews the mechanisms of action and related research progress of astaxanthin on exercise-induced fatigue,and discusses its application value and challenges based on the current status.
基金supported by the National Science Fund for Distinguished Young Scholars of China(31925031)Mount Tai Industrial Blue Talent Program of Shandong Province(tsls20231209)。
文摘Oxidative stress is considered as a critical factor in the process of pathological diseases,and mitochondria are considered as vital target organelles for disease intervention.The purpose of this study was aimed to evaluate the antioxidant efficacy of mitochondria-targeted astaxanthin nanoparticle on hydrogen peroxideinduced oxidative damage.As expected,mitochondria-targeted nanoparticle showed excellent mitochondria co-localization ability with higher Pearson's correlation coefficient(r=0.88).In vitro experiments suggested that the mitochondria-targeted astaxanthin nanoparticle could promote cell viability and increase antioxidantrelated enzyme activities.Simultaneously,metabolomics analysis indicated that mitochondria-targeted astaxanthin nanoparticle could alleviate oxidative stress by regulating amino acid metabolism and energy metabolism.Altogether,all these results strongly confirmed the mitochondria-targeted strategy for astaxanthin delivery could relieve oxidative stress and had great promise in the application of disease intervention.
基金Supported by the National Natural Science Foundation of China(Nos.42177459,41776156,41271521)。
文摘Saline treatment is a low-cost,simple,and effective method to stimulate astaxanthin accumulation in Haematococcus pluvialis,and is proposed to be applied in the second stage of a 2-stage culture since it does not necessitate changing the medium.To understand the effect of salinity on the astaxanthin production of H.pluvialis,the photosynthetic activity and the biocomponents production in 1-and 2-stage cultures in different salinities were investigated.Except for astaxanthin synthesis,which increased at low salinities of 2 and 5-g/L NaCl,most biocomponent yields decreased in 1-stage cultures as salinity increased.At a salinity of 5-g/L NaCl,the 2-stage culture further increased astaxanthin production to 18.41±0.24 mg/L,which was more than 2.0 times that of the control.Saline treatment led to an overall decrease in photosynthetic performance indices of H.pluvialis,and had an impact on five sites of the electron transport chain:the energy connection between antenna and reaction center of photosystemⅡ(PSⅡ),oxygen evolving complex activity on the donor side,the electron transfer from plastoquinone A(Q_(A))to plastoquinone B(Q_(B))and from plastoquinone(PQ)to receptor side of photosystem I(PS I),and the pool size of the end electron acceptors in PSⅠacceptor side.The excitation imbalance between PSⅠand PSⅡcaused by the variance in the electron transfer chain necessitated the synthesis of antioxidants like astaxanthin in order to ensure cell viability.The accumulation of astaxanthin was found to be closely correlated with the stabilized or enhanced the maximum relative electron transfer rate(rETR_(max))and the PSⅡactual quantum yield(QY_(SS))as well as the increased fluorescence yield at J-step(V_(J)).This work offers the novel insight of how saline stress controls H.pluvialis photosynthetic activity and astaxanthin synthesis.
基金supported by the National Natural Science Foundation of China(32302063)Shandong Provincial Natural Science Foundation(ZR2023QC130)。
文摘Autophagy directly regulates the amyloid beta-peptide(Aβ)clearance,and its dysfunction occurs in the early pathogenesis of Alzheimer's disease(AD).We previously reported that docosahexaenoic acid-acylated astaxanthin monoester(AST-DHA)showed neuroprotection against AD pathology.However,its in-depth mechanism and autophagic responses in AD brains are poorly understood.Herein,SH-SY5Y cells overexpressing the Swedish mutation(K595N/M596L)of APP gene were established to preliminarily evaluate the actions of AST-DHA on reducing Aβ_(1-42)levels and regulating autophagy.In microglial BV2 cells,AST-DHA and free astaxanthin(F-AST)recovered p62 and LC3Ⅱ/Ⅰlevels,and restored autophagy flux by rescuing the late phase of microglial autophagy.Notably,autophagic inhibitor bafilomycin A1 blunted the abilities of AST-DHA to reduce Aβ_(1-42)and fibral Aβ,suggesting that AST-DHA probably promoted Aβclearance in a microglial autophagy-dependent manner.Further studies in APP/PS1 mice verified that dietary AST-DHA and F-AST promoted Aβphagocytosis via microglial autophagy.Significant decreases of Iba1 and p62 were observed around Aβplaque in the hippocampus and cortex using triple fluorescence staining.Furthermore,AST-DHA exhibited superior performance over F-AST in restoring autophagic dysfunction,ameliorating Aβburden and cognitive deficit.Our findings suggest a possible mechanism of AST-DHA in improving AD by which it restores microglial autophagy to facilitate cerebral Aβclearance.It supports the future application of AST-DHA as an autophagic regulator in maintaining brain function.
基金the Fundamental Research Funds for the Central Universities(No.202351011)。
文摘Astaxanthin(AX)and vitamin E(VE)are widely consumed nutritional supplements in China,with its beneficial effects predominantly attributed to all-trans AX and VE.The aim of this study is to develop and validate a rapid and accurate method for quantifying the content of AX and VE in nutritional supplement products using highly sensitive1H NMR method.Coumarin was chosen as the internal standard.Specific signals from AX was optimal at H-7,7'in the chemical shift range ofδ6.17–6.24 ppm,whereas the signals of VE atδ2.59 ppm.To demonstrate the reliability of this analytical approach the proposed method underwent rigorous validation,specificity,limit of detection(LOD),limit of quantitation(LOQ),linearity,accuracy,precision,and recovery.The accuracy of the validation method was 3.10%for AX and 1.99%for VE.The results indicated that the method was precise and reliable.The method has been successfully applied to simultaneous quantification of AX and VE in nutritional supplements products.
基金For financial support,the authors gratefully acknowledge the National Natural Science Foundation of China(U2004164)the National Key Research and Development Program of China(2018YFC1106703)the Key Projects of the Joint Fund of the National Natural Science Foundation of China(U1804251).
文摘The cardiovascular diseases(CVD)continue to be the major threat to global public health over the years,while one of the effective methods to treat CVD is stent intervention.Biomedical magnesium(Mg)alloys have great potential applications in cardiovascular stents benefit from their excellent biodegradability and absorbability.However,excessive degradation rate and the delayed surface endothelialization still limit their further application.In this study,we modified a Mg-Zn-Y-Nd alloy(ZE21B)by preparing MgF_(2) as the corrosion resistance layer,the dopamine polymer film(PDA)as the bonding layer,and hyaluronic acid(HA)loaded astaxanthin(ASTA)as an important layer to directing the cardiovascular cells fate.The electrochemical test results showed that the MgF_(2)/PDA/HA-ASTA coating improved the corrosion resistance of ZE21B.The cytocompatibility experiments also demonstrated that this novel composite coating also selectively promoted endothelial cells proliferation,inhibited hyperproliferation of smooth muscle cells and adhesion of macrophages.Compared with the HAloaded rapamycin(RAPA)coating,our MgF_(2)/PDA/HA-ASTA coating showed better blood compatibility and cytocompatibility,indicating stronger multi-functions for the ZE21B alloy on cardiovascular application.
