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KMID : 1123920150290010018
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Korean Journal of Oriental Physiology and Pathology
2015 Volume.29 No. 1 p.18 ~ p.26
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Akebiae Caulis Inhibits Oxidative Stress through AMPK Activation
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Jung Eun-Hye
Kim Sang-Chan
Cho Il-Je
Kim Young-Woo
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Abstract
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Akebiae Caulis is a galenical originated from Akebia quinata Decaisne species. It is commonly used in the treatment of oposiuria, inflammation, nociceptive and fever. Here, we investigated the effect of Akebiae Caulis extract (ACE) to protect hepatocyte against the malfunction of mitochondria and apoptosis. Arachidonic acid (AA)+iron promoted excessive reactive oxygen species (ROS) production and exerted a deleterious effect on mitochondria. Treatment with ACE protected hepatocytes from AA+iron-induced cytotoxicity, as shown by alterations in the protein levels related with apoptosis such as poly(ADP-ribose) polymerase, pro-caspase 3, Bcl-XL and Bcl-2. Moreover, AA+iron-induced H₂O₂ production, GSH depletion and mitochondrial dysfunction were alleviated by ACE pretreatment. As a potential molecular mechanism for the ACE-mediated cytoprotection, phosphorylation of AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death, was increased by ACE. Moreover, ACE treatment enhanced inactive phosphorylation of glycogen synthase kinase-3β (GSK3β), downstream substrate kinase of AMPK. More importantly, ACE prevented a decrease in the GSK3β phosphorylation derived by AA+iron, which might contribute to mitohondiral protection and cell survival. To further identify essential compounds in Akebiae Caulis for the protection of AA+iron-mediated cytotoxicity, we found that betulin in combination with hederagenin protected from AA+iron-induced mitochondrial dysfunction. Betulin+hederagenin treatment also increased inactive phosphorylation of GSK3β in common with ACE. These results suggest that ACE protected hepatocytes against oxidative stress and mitochondrial dysfunction, which is mediated with inactive GSK3β phosphorylation downstream of AMPK.
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KEYWORD
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Akebiae caulis, GSK3β, AMPK, arachidonic acid, iron
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