Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in ...Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.展开更多
Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cul...Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cultured neonate rat were cultured in medium with 200 μmol/L H2O2, and the medium was supplemented with tanshinone ⅡA (1 × 10-4 mol/L) in advance for 24 h. PHB in myocardial cells was knocked down by RNA interference, and the expression level of PHB was determined by Western blotting analysis. Flow cytometric analysis was used to detect apoptosis rate, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane potential (MMP). Results H2O2-mediated cell apoptosis resulted in activation of PHB, increasing of [Ca2+]i, and decreasing of MMP. Tanshinone ⅡA profoundly inhibited myocardial cell apoptosis induced by H2O2, decreased [Ca2+]i, and increased MMP. Specific silence of PHB by siRNA down-regulated the expression level of PHB, increased apoptosis rate and [Ca2+]i, and decreased MMP. Conclusion The results demonstrate that tanshinone ⅡA could attenuate apoptosis induced by H2O2, and the activation of PHB induced by H2O2 is the major regulatory pathway of cyto-protective gene expression against oxidative stress.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
基金supported by the National Natural Science Foundation of China,No.81273983
文摘Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.
基金National Natural Sciences Foundation of China (30572435)
文摘Objective To investigate the anti-apoptotic mechanism of tanshinone ⅡA and the function of prohibitin (PHB) on myocardial cells apoptosis induced by hydrogen peroxide (H2O2). Methods Myocardial cells were primary cultured neonate rat were cultured in medium with 200 μmol/L H2O2, and the medium was supplemented with tanshinone ⅡA (1 × 10-4 mol/L) in advance for 24 h. PHB in myocardial cells was knocked down by RNA interference, and the expression level of PHB was determined by Western blotting analysis. Flow cytometric analysis was used to detect apoptosis rate, intracellular calcium concentration ([Ca2+]i), and mitochondrial membrane potential (MMP). Results H2O2-mediated cell apoptosis resulted in activation of PHB, increasing of [Ca2+]i, and decreasing of MMP. Tanshinone ⅡA profoundly inhibited myocardial cell apoptosis induced by H2O2, decreased [Ca2+]i, and increased MMP. Specific silence of PHB by siRNA down-regulated the expression level of PHB, increased apoptosis rate and [Ca2+]i, and decreased MMP. Conclusion The results demonstrate that tanshinone ⅡA could attenuate apoptosis induced by H2O2, and the activation of PHB induced by H2O2 is the major regulatory pathway of cyto-protective gene expression against oxidative stress.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
