Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

蒙古黄芪总黄酮对大鼠心肌缺血再灌注损伤的保护作用

目的研究蒙古黄芪总黄酮对大鼠心肌缺血再灌注损伤的保护作用及其机制。方法采用结扎大鼠左冠状动脉前降支法,缺血90 min,再灌注24 h,建立心肌缺血再灌注损伤模型。观察大鼠心电图S-T段变化,用氯化三苯基四氮唑(TTC)对心肌染色,观察心肌梗死面积及测定血清乳酸脱氢酶、肌酸激酶、心肌组织超氧化物歧化酶、丙二醛含量,探讨蒙古黄芪总黄酮对心肌缺血再灌注损伤的保护作用。结果蒙古黄芪总黄酮90、270 mg·kg-1可以使心肌缺血再灌注损伤大鼠心电图S-T段降低及降低大鼠血清中乳酸脱氢酶、肌酸激酶的释放;30、90、270 mg·kg-1剂量可减少大鼠心肌梗死面积;270 mg·kg-1剂量减少大鼠心肌组织丙二醛的产生,提高心肌组织超氧化物歧化酶活力。结论蒙古黄芪总黄酮可以使缺血再灌注损伤大鼠心肌缺血程度降低,减少心肌梗死面积,对缺血再灌注损伤具有一定的保护作用,其作用机制可能通过抑制乳酸脱氢酶、肌酸激酶的释放,降低心肌组织氧化产物丙二醛含量、提高内源性氧自由基清除剂超氧化物歧化酶的活力,减轻缺血再灌注损伤后氧自由基对心肌细胞膜脂质过氧化损伤有关。