Limits...
Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening.

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H - PLoS ONE (2014)

Bottom Line: 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 Aβ1-42.Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment.These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy and Histo-Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

ABSTRACT
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) 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 Aβ-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 Aβ1-42-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 Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 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 Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-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.

Show MeSH

Related in: MedlinePlus

Chemical structure of astragaloside IV.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4048237&req=5

pone-0098866-g001: Chemical structure of astragaloside IV.

Mentions: Astragaloside IV (AS-IV, chemical structure shown in Fig. 1), is a small molecular (MW = 784 Da) saponin purified from Astragalus membranaceus, that has been routinely used in China to treat chronic diseases [21]. It has been reported that AS-IV has an antioxidant effect and the accepted underlying mechanisms include modulation of energy metabolism and Ca2+ homeostasis [22]–[25]. Moreover, AS-IV shows neuroprotective effects on promoting axonal regeneration and reconstruction of neuronal synapses [26]. However, the protective effects of AS-IV against Aβ1-42-induced mitochondrial dysfunction and neuronal death still need to be elucidated. In the present study, we investigated the effects of AS-IV against Aβ1-42-induced mPTP opening in SK-N-SH cells and elucidated the underlying molecular mechanisms.


Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening.

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H - PLoS ONE (2014)

Chemical structure of astragaloside IV.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048237&req=5

pone-0098866-g001: Chemical structure of astragaloside IV.
Mentions: Astragaloside IV (AS-IV, chemical structure shown in Fig. 1), is a small molecular (MW = 784 Da) saponin purified from Astragalus membranaceus, that has been routinely used in China to treat chronic diseases [21]. It has been reported that AS-IV has an antioxidant effect and the accepted underlying mechanisms include modulation of energy metabolism and Ca2+ homeostasis [22]–[25]. Moreover, AS-IV shows neuroprotective effects on promoting axonal regeneration and reconstruction of neuronal synapses [26]. However, the protective effects of AS-IV against Aβ1-42-induced mitochondrial dysfunction and neuronal death still need to be elucidated. In the present study, we investigated the effects of AS-IV against Aβ1-42-induced mPTP opening in SK-N-SH cells and elucidated the underlying molecular mechanisms.

Bottom Line: 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 Aβ1-42.Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment.These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Anatomy and Histo-Embryology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

ABSTRACT
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) 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 Aβ-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 Aβ1-42-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 Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 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 Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-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.

Show MeSH
Related in: MedlinePlus