Protective Effects of Astragaloside IV against Amyloid Beta1-42 Neurotoxicity by Inhibiting the Mitochondrial Permeability Transition Pore Opening.

PloS one

PubMedID: 24905226

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H. Protective Effects of Astragaloside IV against Amyloid Beta1-42 Neurotoxicity by Inhibiting the Mitochondrial Permeability Transition Pore Opening. PLoS ONE. 2014;9(6):e98866.
Mitochondrial dysfunction caused by amyloid ß-peptide (Aß) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aß-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aß1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aß1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (??m), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aß1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aß1-42 rich environment. These data indicate that AS-IV prevents Aß1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.