Isoflavone formononetin（FN） is a main active component of red clover（Trifolium pratense L.）, a medicinal plant possessing antitumorigenic and antioxidant properties. In the present study, we aimed to examine the e...Isoflavone formononetin（FN） is a main active component of red clover（Trifolium pratense L.）, a medicinal plant possessing antitumorigenic and antioxidant properties. In the present study, we aimed to examine the effect of FN on dextran sulfate sodium（DSS）-induced ulcerative colitis（UC） in mice. The results showed that FN（25, 50 mg/kg） markedly attenuated the loss of body weight, the disease activity index（DAI）, shortening of colon length and tissue injury induced by DSS treatment. In addition, the levels of tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6）, and cyclooxygenase-2（COX-2） were also significantly reduced in FN treatment group compared with the DSS group. Moreover, several representative oxidative stress parameters in colorectum, including superoxide dismutase（SOD）, methane dicarboxylic aldehyde（MDA）, myeloperoxidase（MPO） and 8-oxoguanine, were markedly ameliorated. In this study, we also found that the expression of Nrf2 was increased by FN treatment. However, symptoms of UC were not ameliorated in Nrf2 knockout mice. Taken together, FN could prevent the development of UC through activating of Nrf2 axis, and the protective effect was Nrf2 dependent. Our results demonstrated that FN might be a potential therapeutic agent in the treatment of UC.展开更多
Objective:To evaluate the effect of formononetin on type 2 diabetic cardiomyopathy.Methods:Diabetes was induced by feeding high-fat diet for 2 weeks and administration of 35 mg/kg of streptozotocin in rats.Formononeti...Objective:To evaluate the effect of formononetin on type 2 diabetic cardiomyopathy.Methods:Diabetes was induced by feeding high-fat diet for 2 weeks and administration of 35 mg/kg of streptozotocin in rats.Formononetin was administered at 10,20 and 40 mg/kg for 16 weeks once a day.Plasma glucose,lipid parameters,and cardiac markers in blood samples were measured.Body weight and relative heart weight were recorded.Hemodynamic parameters,oxidative stress parameters and silence information regulator 1(SIRT1)expression in cardiac tissue were estimated.Histopathological changes in cardiac tissue were also observed.Results:Formononetin significantly reduced the levels of glucose,triglycerides,cholesterol,low density lipoprotein,creatine kinaseMB,lactate dehydrogenase and aspartate aminotransferase.In addition,formononetin significantly improved hemodynamic parameters,alleviated oxidative stress and increased SIRT1 expression.Conclusions:The study indicates that formononetin can improve hyperglycemia and hyperlipemia,reduce oxidative stress and increase SIRT1 expression.It can be a potential therapeutic agent for diabetic cardiomyopathy.展开更多
Objective Formononetin(FOR),a traditional Chinese medicine,has been widely used for nerve protection and nerve function rehabilitation after cerebral stroke.However,the role of FOR in autophagic lysosome function in c...Objective Formononetin(FOR),a traditional Chinese medicine,has been widely used for nerve protection and nerve function rehabilitation after cerebral stroke.However,the role of FOR in autophagic lysosome function in cerebral ischemiareperfusion damage has not been investigated.This study aimed to explore whether the therapeutic benefits of FOR were influenced by the regulation of autophagy flux.Methods Male Sprague-Dawley rats were separated into sham,model,and MCAO+FOR(30 mg/kg)groups after undergoing middle cerebral artery occlusion(MCAO)and ischemia-reperfusion(I/R).Then,the brain tissues in the ischemic penumbra were obtained to detect the proteins in autophagic/lysosomal pathway with antibodies of Beclin-1,LC3,SQSTM1/P62,Ubiquitin,LAMP-2,Cathepsin B(CTSB)and Cathepsin D(CTSD)by Western blot and immunofluorescence,respectively.Meanwhile,the therapeutic effectiveness was evaluated by measuring infarct volume,neurological impairments,and neuronal necrosis.Results The findings of this study demonstrate that FOR treatment exhibits a dual effect by enhancing the autophagic activities of Beclin-1 and LC3 in neurons,while simultaneously improving the autophagic clearance function,as evidenced by reinforced lysosomal activities of LAMP-2,CTSB,and CTSD,as well as reduced autophagic accumulation of Ubiquitin and P62 in the MCAO+FOR group compared to the MCAO group.Additionally,7 d of FOR treatment dramatically reduced neurological deficits,infarct volume,and neuronal death caused by cerebral ischemia.Conclusion These findings suggest that the neuroprotective mechanism of FOR therapy in accelerating recovery from ischemic stroke may involve the increase of autophagy flux in the penumbra.展开更多
Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxi...Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxidant,antidepressant,anxiolytic and other pharmacological effects.This paper summarizes the pharmacological action and molecular mechanism of formononetin,in order to provide a theoretical basis for the development and clinical application of formononetin.展开更多
Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whe...Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whether FMN ameliorated HFpEF-induced cardiac dysfunction and exploring its underlying mechanisms.Methods:The mouse model of HFpEF was established through uninephrectomy surgery and d-aldosterone infusion in C57BL/6 mice.Cardiac remodeling and potential mechanisms of FMN in HFpEF were assessed by histological analysis,immunofluorescence,echocardiography,real-time PCR and western blotting sequentially.Results:FMN prevented myocardial dysfunction,fibrosis and cardiomyocyte apoptosis.The mRNA levels of left ventricular hypertrophy markers were increased in HFpEF mice but they remained unchanged in FMN-treated mice.In addition,the expression levels of PPARαand PGC-1 were increased in HFpEF mice for FMN treatment.The PPARα-PGC-1 complex affected the expression of fatty acid content and encoded enzymes in glucose metabolism.Both the hypertrophy and metabolic impairment due to FMN in HFpEF mice were alleviated after the addition of PPARαantagonist GW6471.Conclusion:In conclusion,FMN could prevent the cardiac hypertrophy in HFpEF mice by activating the PPARα/PGC-1 pathway and regulating energy metabolism,which provides a new therapeutic strategy for HFpEF patients.展开更多
Objective The objective of this article is to explore the effect of formononetin(FMN)on depressive-like behaviors and neuroinflammation in lipopolysaccharide(LPS)-induced mice.Methods After acclimatization,male Instit...Objective The objective of this article is to explore the effect of formononetin(FMN)on depressive-like behaviors and neuroinflammation in lipopolysaccharide(LPS)-induced mice.Methods After acclimatization,male Institute of Cancer Research mice were randomly divided into normal group,LPS group,paroxetine group(20mg/kg),FMN low-dose group(20 mg/kg,FMN20),and FMN high-dose group(40 mg/kg,FMN40),with eight mice in each group.The depressive-like behaviors were observed by sucrose preference test,tail suspension test(TST),and open field test.The protein and mRNA levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the hippocampus were determined by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction.The expression level of ionized calciumbinding adapter molecule 1(Iba-1)in the hippocampus was observed by immunofluorescence staining to evaluate the activation level of microglia.Results Compared with the control group,the sucrose preference rate,the activity time of the central area,the distance of the central area,and the number of times of entering the central area were significantly decreased in the LPS group(p<0.01),and the immobility time of TSTwas significantly prolonged(p<0.05),the expression levels of IL-6,IL-1β,and TNF-αprotein and mRNA in hippocampus were significantly increased(p<0.01),and the fluorescence intensity of Iba-1 in CA1,CA3,and DG regions of hippocampus was significantly increased(p<0.01).Compared with the LPS group,the sucrose preference rate,central area activity time,central area activity distance,and the number of times of entering the central area were significantly increased(p<0.05 or p<0.01)in the FMN group,and TST immobility time was significantly shortened(p<0.01),the expression levels of IL-6,IL-1β,and TNF-αprotein and mRNA in the hippocampus were significantly decreased(p<0.05 or p<0.01),and the fluorescence intensity of Iba-1 in CA1,CA3,and DG regions of hippocampus was significantly decreased(p<0.01).Conclusion FMN could inhibit LPS-induced activation of microglia,reduce hippocampal neuroinflammation,and improve depressive-like behaviors in mice.展开更多
目的基于中药超分子(supramolecules of traditional Chinese medicine,STCM)理论,系统探讨黄芪Astragali Radix-莪术Curcumae Rhizoma(AC)药对协同增效抗肝癌的物质基础,旨在揭示其配伍的科学内涵。方法采用离心-透析法对STCM进行分离...目的基于中药超分子(supramolecules of traditional Chinese medicine,STCM)理论,系统探讨黄芪Astragali Radix-莪术Curcumae Rhizoma(AC)药对协同增效抗肝癌的物质基础,旨在揭示其配伍的科学内涵。方法采用离心-透析法对STCM进行分离;并借助动态光散射(dynamic light scattering,DLS)技术和透射电子显微镜(transmission electron microscope,TEM)对其粒径、形貌进行表征,结合光谱技术分析其形成机制;进一步利用液相色谱-质谱联用(liquid chromatograph mass spectrometer,LC-MS)技术分析其化学成分;并对其体外抗肝癌活性进行评价。结果黄芪-莪术合煎液与物理混合液中均存在STCM,但黄芪-莪术合煎液中STCM(AC-STCM)的粒径更小、分布更均匀且稳定性更高;其自组装过程中可能由毛蕊异黄酮、芒柄花素、双去甲氧基姜黄素等成分通过氢键和π-π堆积作用共同驱动;AC-STCM对人肝癌HepG2细胞具有显著抑制作用(P<0.01),其体外抗肿瘤活性显著优于合煎液、物理混合STCM(Mix-STCM)(P<0.01),同时,合煎液本身的抗肿瘤效果亦优于物理混合液(P<0.01)。结论在煎煮过程中,黄芪-莪术药对通过非共价键实现成分的自组装,形成稳定的STCM体系,构成其协同增效抗肝癌作用的重要物质基础。首次从STCM的新视角阐释黄芪-莪术药对协同增效抗肝癌的科学内涵,为中药复方配伍理论的现代化研究提供理论依据与实验基础。展开更多
This study aims to characterize formononetin(FMN)and perilla seed oil(PSO)co-loaded nanostructured lipid carriers(NLC).FMN-PSO-NLC was prepared by melt-emulsification ultrasonic method.The average particle size of FMN...This study aims to characterize formononetin(FMN)and perilla seed oil(PSO)co-loaded nanostructured lipid carriers(NLC).FMN-PSO-NLC was prepared by melt-emulsification ultrasonic method.The average particle size of FMN-PSO-NLC was 117.5±3.7 nm,with PDI of 0.240±0.017 and zeta potential of-36.7±0.7 mV.Dif-ferential scanning calorimetry(DSC),X-ray diffractometry(XRD),and Fourier transform infrared spectroscopy(FTIR)studies revealed that the formation of FMN-PSO-NLC was accompanied by changes in crystallinity and intermolecular interactions.FMN-PSO-NLC dispersions possessed pseudoplastic flow from the rheological studies.FMN-PSO-NLC possessed sustained-release of FMN for 24 h.FMN-PSO-NLC was more easily digested than that of PSO in vitro digestion.The antioxidant activity and stability of FMN-PSO-NLC were significantly improved.This study provides a formulation design for improving the stability,antioxidant activity of FMN and delaying the oxidation of PSO.展开更多
基金National Natural Science Foundation of China(Grant No.81274150,81573680 and 81470179)
文摘Isoflavone formononetin（FN） is a main active component of red clover（Trifolium pratense L.）, a medicinal plant possessing antitumorigenic and antioxidant properties. In the present study, we aimed to examine the effect of FN on dextran sulfate sodium（DSS）-induced ulcerative colitis（UC） in mice. The results showed that FN（25, 50 mg/kg） markedly attenuated the loss of body weight, the disease activity index（DAI）, shortening of colon length and tissue injury induced by DSS treatment. In addition, the levels of tumor necrosis factor-α（TNF-α）, interleukin-6（IL-6）, and cyclooxygenase-2（COX-2） were also significantly reduced in FN treatment group compared with the DSS group. Moreover, several representative oxidative stress parameters in colorectum, including superoxide dismutase（SOD）, methane dicarboxylic aldehyde（MDA）, myeloperoxidase（MPO） and 8-oxoguanine, were markedly ameliorated. In this study, we also found that the expression of Nrf2 was increased by FN treatment. However, symptoms of UC were not ameliorated in Nrf2 knockout mice. Taken together, FN could prevent the development of UC through activating of Nrf2 axis, and the protective effect was Nrf2 dependent. Our results demonstrated that FN might be a potential therapeutic agent in the treatment of UC.
文摘Objective:To evaluate the effect of formononetin on type 2 diabetic cardiomyopathy.Methods:Diabetes was induced by feeding high-fat diet for 2 weeks and administration of 35 mg/kg of streptozotocin in rats.Formononetin was administered at 10,20 and 40 mg/kg for 16 weeks once a day.Plasma glucose,lipid parameters,and cardiac markers in blood samples were measured.Body weight and relative heart weight were recorded.Hemodynamic parameters,oxidative stress parameters and silence information regulator 1(SIRT1)expression in cardiac tissue were estimated.Histopathological changes in cardiac tissue were also observed.Results:Formononetin significantly reduced the levels of glucose,triglycerides,cholesterol,low density lipoprotein,creatine kinaseMB,lactate dehydrogenase and aspartate aminotransferase.In addition,formononetin significantly improved hemodynamic parameters,alleviated oxidative stress and increased SIRT1 expression.Conclusions:The study indicates that formononetin can improve hyperglycemia and hyperlipemia,reduce oxidative stress and increase SIRT1 expression.It can be a potential therapeutic agent for diabetic cardiomyopathy.
文摘Objective Formononetin(FOR),a traditional Chinese medicine,has been widely used for nerve protection and nerve function rehabilitation after cerebral stroke.However,the role of FOR in autophagic lysosome function in cerebral ischemiareperfusion damage has not been investigated.This study aimed to explore whether the therapeutic benefits of FOR were influenced by the regulation of autophagy flux.Methods Male Sprague-Dawley rats were separated into sham,model,and MCAO+FOR(30 mg/kg)groups after undergoing middle cerebral artery occlusion(MCAO)and ischemia-reperfusion(I/R).Then,the brain tissues in the ischemic penumbra were obtained to detect the proteins in autophagic/lysosomal pathway with antibodies of Beclin-1,LC3,SQSTM1/P62,Ubiquitin,LAMP-2,Cathepsin B(CTSB)and Cathepsin D(CTSD)by Western blot and immunofluorescence,respectively.Meanwhile,the therapeutic effectiveness was evaluated by measuring infarct volume,neurological impairments,and neuronal necrosis.Results The findings of this study demonstrate that FOR treatment exhibits a dual effect by enhancing the autophagic activities of Beclin-1 and LC3 in neurons,while simultaneously improving the autophagic clearance function,as evidenced by reinforced lysosomal activities of LAMP-2,CTSB,and CTSD,as well as reduced autophagic accumulation of Ubiquitin and P62 in the MCAO+FOR group compared to the MCAO group.Additionally,7 d of FOR treatment dramatically reduced neurological deficits,infarct volume,and neuronal death caused by cerebral ischemia.Conclusion These findings suggest that the neuroprotective mechanism of FOR therapy in accelerating recovery from ischemic stroke may involve the increase of autophagy flux in the penumbra.
基金Supported by Central Government Supports Local College Reform and Development Fund Talent Training Projects(2020GSP16)Undergraduate Innovation and Entrepreneurship Training Program of Heilongjiang Province(202310223122).
文摘Formononetin is an isoflavone phytoestrogen mainly existing in leguminous plants such as Trifolium pretense,Spatholobus suberectus,etc.Studies have proved that formononetin has good anti-inflammatory,antitumor,antioxidant,antidepressant,anxiolytic and other pharmacological effects.This paper summarizes the pharmacological action and molecular mechanism of formononetin,in order to provide a theoretical basis for the development and clinical application of formononetin.
基金supported by the National Natural Science Foundation of China(82274313)Key R&D Program of Shaanxi Province(2023GHZD43)the National Natural Science Foundation of China(81870284).
文摘Background:Formononetin(FMN)has beneficial effects in cardiovascular diseases but its functions and mechanisms in heart failure with preserved ejection fraction(HFpEF)remain unclear.This study aimed at determining whether FMN ameliorated HFpEF-induced cardiac dysfunction and exploring its underlying mechanisms.Methods:The mouse model of HFpEF was established through uninephrectomy surgery and d-aldosterone infusion in C57BL/6 mice.Cardiac remodeling and potential mechanisms of FMN in HFpEF were assessed by histological analysis,immunofluorescence,echocardiography,real-time PCR and western blotting sequentially.Results:FMN prevented myocardial dysfunction,fibrosis and cardiomyocyte apoptosis.The mRNA levels of left ventricular hypertrophy markers were increased in HFpEF mice but they remained unchanged in FMN-treated mice.In addition,the expression levels of PPARαand PGC-1 were increased in HFpEF mice for FMN treatment.The PPARα-PGC-1 complex affected the expression of fatty acid content and encoded enzymes in glucose metabolism.Both the hypertrophy and metabolic impairment due to FMN in HFpEF mice were alleviated after the addition of PPARαantagonist GW6471.Conclusion:In conclusion,FMN could prevent the cardiac hypertrophy in HFpEF mice by activating the PPARα/PGC-1 pathway and regulating energy metabolism,which provides a new therapeutic strategy for HFpEF patients.
基金supported by the National Natural Science FoundationofChina(81973739,82274496)Henan Province Outstanding Youth Science Foundation(202300410249).
文摘Objective The objective of this article is to explore the effect of formononetin(FMN)on depressive-like behaviors and neuroinflammation in lipopolysaccharide(LPS)-induced mice.Methods After acclimatization,male Institute of Cancer Research mice were randomly divided into normal group,LPS group,paroxetine group(20mg/kg),FMN low-dose group(20 mg/kg,FMN20),and FMN high-dose group(40 mg/kg,FMN40),with eight mice in each group.The depressive-like behaviors were observed by sucrose preference test,tail suspension test(TST),and open field test.The protein and mRNA levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the hippocampus were determined by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction.The expression level of ionized calciumbinding adapter molecule 1(Iba-1)in the hippocampus was observed by immunofluorescence staining to evaluate the activation level of microglia.Results Compared with the control group,the sucrose preference rate,the activity time of the central area,the distance of the central area,and the number of times of entering the central area were significantly decreased in the LPS group(p<0.01),and the immobility time of TSTwas significantly prolonged(p<0.05),the expression levels of IL-6,IL-1β,and TNF-αprotein and mRNA in hippocampus were significantly increased(p<0.01),and the fluorescence intensity of Iba-1 in CA1,CA3,and DG regions of hippocampus was significantly increased(p<0.01).Compared with the LPS group,the sucrose preference rate,central area activity time,central area activity distance,and the number of times of entering the central area were significantly increased(p<0.05 or p<0.01)in the FMN group,and TST immobility time was significantly shortened(p<0.01),the expression levels of IL-6,IL-1β,and TNF-αprotein and mRNA in the hippocampus were significantly decreased(p<0.05 or p<0.01),and the fluorescence intensity of Iba-1 in CA1,CA3,and DG regions of hippocampus was significantly decreased(p<0.01).Conclusion FMN could inhibit LPS-induced activation of microglia,reduce hippocampal neuroinflammation,and improve depressive-like behaviors in mice.
文摘目的基于中药超分子(supramolecules of traditional Chinese medicine,STCM)理论,系统探讨黄芪Astragali Radix-莪术Curcumae Rhizoma(AC)药对协同增效抗肝癌的物质基础,旨在揭示其配伍的科学内涵。方法采用离心-透析法对STCM进行分离;并借助动态光散射(dynamic light scattering,DLS)技术和透射电子显微镜(transmission electron microscope,TEM)对其粒径、形貌进行表征,结合光谱技术分析其形成机制;进一步利用液相色谱-质谱联用(liquid chromatograph mass spectrometer,LC-MS)技术分析其化学成分;并对其体外抗肝癌活性进行评价。结果黄芪-莪术合煎液与物理混合液中均存在STCM,但黄芪-莪术合煎液中STCM(AC-STCM)的粒径更小、分布更均匀且稳定性更高;其自组装过程中可能由毛蕊异黄酮、芒柄花素、双去甲氧基姜黄素等成分通过氢键和π-π堆积作用共同驱动;AC-STCM对人肝癌HepG2细胞具有显著抑制作用(P<0.01),其体外抗肿瘤活性显著优于合煎液、物理混合STCM(Mix-STCM)(P<0.01),同时,合煎液本身的抗肿瘤效果亦优于物理混合液(P<0.01)。结论在煎煮过程中,黄芪-莪术药对通过非共价键实现成分的自组装,形成稳定的STCM体系,构成其协同增效抗肝癌作用的重要物质基础。首次从STCM的新视角阐释黄芪-莪术药对协同增效抗肝癌的科学内涵,为中药复方配伍理论的现代化研究提供理论依据与实验基础。
基金supported by Livelihood Plan Project of Department of Science and Technology of Liaoning Province(2021JH2/10300069,2019-ZD-0845)Department of Education of Liaoning Province(LJKZ0918).
文摘This study aims to characterize formononetin(FMN)and perilla seed oil(PSO)co-loaded nanostructured lipid carriers(NLC).FMN-PSO-NLC was prepared by melt-emulsification ultrasonic method.The average particle size of FMN-PSO-NLC was 117.5±3.7 nm,with PDI of 0.240±0.017 and zeta potential of-36.7±0.7 mV.Dif-ferential scanning calorimetry(DSC),X-ray diffractometry(XRD),and Fourier transform infrared spectroscopy(FTIR)studies revealed that the formation of FMN-PSO-NLC was accompanied by changes in crystallinity and intermolecular interactions.FMN-PSO-NLC dispersions possessed pseudoplastic flow from the rheological studies.FMN-PSO-NLC possessed sustained-release of FMN for 24 h.FMN-PSO-NLC was more easily digested than that of PSO in vitro digestion.The antioxidant activity and stability of FMN-PSO-NLC were significantly improved.This study provides a formulation design for improving the stability,antioxidant activity of FMN and delaying the oxidation of PSO.
