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
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
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
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
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 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.
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.
