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. 2017 Jan 6;9(1):41.
doi: 10.3390/nu9010041.

Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats

Gyeong-Ji Kim  1 , Da Hye Song  2 , Han Seok Yoo  3 , Kang-Hyun Chung  4 , Kwon Jai Lee  5 , Jeung Hee An  6
Affiliations

Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats

Gyeong-Ji Kim et al. Nutrients. .

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.

Keywords: ALDH2; alcohol; apoptosis; hederagenin; inflammatory; liver disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flows diagram of extraction and isolation of hederagenin from Akebia quinata (A); and suppressive effect of hederagenin against Nitric oxide generation in RAW 264.7 cells (B).
Figure 2
Figure 2
Histological features of representative liver and kidney sections stained with hematoxylin–eosin (H&E) after chronic ethanol consumption. Typical images were chosen from each experimental group (original magnification ×100).
Figure 3
Figure 3
Effects of hederagenin on mRNA expression of ADH and ALDH2 assessed using RT-PCR. Results are expressed as the means ± SD. Significant differences (p < 0.05) are represented using different letters. ADH, alcohol dehydrogenase; ALDH, acetaldehyde dehydrogenase.
Figure 4
Figure 4
Effect of hederagenin on inflammation-related gene expression in the livers of ethanol-exposed rats (A); and mRNA expression of the liver TNF-α, IL-6, and COX-2 assessed using RT-PCR (B). The liver concentration of TNF-α and IL-6 was determined using an enzyme-linked immunosorbent assay. Results are expressed as the means ± SD. Significant differences (p < 0.05) are represented using different letters. TNF, tumor necrosis factor; IL, interleukin; COX, cyclooxygenase.
Figure 5
Figure 5
Effects of hederagenin on apoptotic signaling cascades in ethanol-treated hepatocytes. Extracts of the liver proteins from the different groups were subjected to Western blotting. Expression levels of cytoplasmic Bcl-2, Bax, Bcl-X, and p53 are shown. Results are expressed as the means ± SD. Significant differences (p < 0.05) are represented using different letters.
Figure 6
Figure 6
Effects of hederagenin on the expression levels of p-AKT, p-ERK, and p-p38 in the liver of ethanol-exposed rats. Results are expressed as the means ± SD. Significant differences (p < 0.05) are represented using different letters.
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