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

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.

Do genetic polymorphisms of B-cell CLL/lymphoma 2 confer susceptibility to anti-tuberculous therapy-associated drug-induced liver injury?

“…This sentence can be changed as follow: By reducing the interaction with Bax, Bcl2 regulates autophagy (Flora et al, 2007), and thus participates in alcoholic liver disease. The Bax/Bcl2 ratio is currently applied to assess alcoholic liver disease, and some novel candidates targeting Bcl2 have been studied for the treatment of alcoholic liver disease (Kim et al, 2017a;Zhu et al, 2017). Bcl2 is related to the development of cholestatic liver injury.…”

<em>Akebia quinata</em> Extract Combined with Korean Traditional Juice Activates Antioxidant Enzymes and Reduces Apoptosis and Inflammation

“…Upregulation of ADH increases susceptibility to ethanol toxicity in hepatic cells while increased ALDH has a protective effect on alcohol-induced liver injury [18]. Moreover, CYP2E1-dependent microsomal alcohol oxidative stress system, was an important pathway of alcohol metabolism in the liver [19].…”

“…Especially, the release of inflammatory cytokines, such as COX-2, TNF-α and IL-6 can induced to hepatocyte apoptosis [18]. Decreases in COX-2, TNF-α and IL-6 levels have been used as important regulators of an inflammatory response to potentially toxic agents [18].…”

Oleanolic Acid Induces p53 Dependent Apoptosis via the ERK/JNK/AKT Pathway in Cancer Cell Lines

“…The p53 tumor suppressor is activated by oncogene-or DNA damage-induced signaling pathways, and accelerate the transcription of several genes that are involved in apoptosis, proapoptotic members of the Bcl-2 family and including those encoding for death receptors. [8]. Bax is an important proapoptotic member of the Bcl-2 family of proteins that regulates the balance between cellular survival and death [9].…”

“…In response to apoptosis signals, Bax is transformed into a fatal mitochondrial oligomer that causes mitochondrial damage; this represents an important step for the intrinsic apoptosis pathway [10,11]. In addition, the p53-induced apoptosis induces the activation of caspases [8]. Caspase activation primarily occurs through the activation of the death receptor pathway or through mitochondrial membrane depolarization [6].…”