Abstract
In this study, we determined the effects of hederagenin isolated from Akebia quinata fruit on alcohol-induced hepatotoxicity in rats. Specifically, we investigated the hepatoprotective, anti-inflammatory, and anti-apoptotic effects of hederagenin, as well as the role of AKT and mitogen-activated protein kinase (MAPK) signaling pathways in ethanol-induced liver injury. Experimental animals were randomly divided into three groups: normal (sham), 25% ethanol, and 25% ethanol + hederagenin (50 mg/kg/day). Each group was orally administered the respective treatments once per day for 21 days. Acetaldehyde dehydrogenase-2 mRNA expression was higher and alcohol dehydrogenase mRNA expression was lower in the ethanol + hederagenin group than those in the ethanol group. Pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2, significantly increased in the ethanol group, but these increases were attenuated by hederagenin. Moreover, Western blot analysis showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin. Hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK. Hederagenin alleviated ethanol-induced liver damage through anti-inflammatory and anti-apoptotic activities. These results suggest that hederagenin is a potential candidate for preventing alcoholic liver injury.
Highlights
Adolescent alcohol consumption has been associated with negative health and social consequences in Korea [1]
We report for the first time the effects of hederagenin isolated from the Akebia quinata fruit on apoptotic and cytokine pathways associated with alcohol exposure
The data in the present study show a suppressive effect on NO generation following treatment with hederagenin attributable to inhibition of the de novo synthesis and catalytic activity of inducible nitric oxide synthase in RAW 264.7 cells
Summary
Adolescent alcohol consumption has been associated with negative health and social consequences in Korea [1]. Alcohol-related liver disease showed a major cause of morbidity and mortality worldwide [2]. Alcoholic liver disease is characterized by lipid accumulation, inflammation and apoptosis, leading to cirrhosis, fibrosis and liver cancer [3]. Several studies have shown that oxidative stress and acetaldehyde play an pivotal role in the pathogenesis of alcoholic liver disease, including hepatocyte dysfunction, inflammation, apoptosis, and fibrosis [1,2,3]. Ethanol is oxidized to a toxic form, acetaldehyde, by alcohol dehydrogenase (ADH). Acetaldehyde is oxidized to acetic acid, which is non-toxic, by acetaldehyde dehydrogenase (ALDH) [4]. Acetaldehyde can combine with proteins and form aldehyde protein adducts that lead to protein dysfunction and result in the creation of antigens that contribute to Nutrients 2017, 9, 41; doi:10.3390/nu9010041 www.mdpi.com/journal/nutrients
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