title: Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats.
abstract: In this study, we determined the effects of hederagenin isolated fromAkebia quinatafruit 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.
authors.affiliation: Division of Food Bioscience, Konkuk University, Chunju 27478, Korea. kgj8495@hanmail.net.
authors.forename: Gyeong-Ji
authors.initials: GJ
authors.lastname: Kim
authors.affiliation: Division of Food Bioscience, Konkuk University, Chunju 27478, Korea. sdh5740@naver.com.
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Song
authors.affiliation: Department of Food Science and Technology, Seoul National University of Science & Technology, Seoul 01811, Korea. yhs0223@naver.com.
authors.forename: Han Seok
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: Department of Food Science and Technology, Seoul National University of Science & Technology, Seoul 01811, Korea. carl@seoultech.ac.kr.
authors.forename: Kang-Hyun
authors.initials: KH
authors.lastname: Chung
authors.affiliation: Department of Advanced Materials Engineering, Daejeon University, Daejeon 34520, Korea. jmul@ssu.ac.kr.
authors.forename: Kwon Jai
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Division of Food Bioscience, Konkuk University, Chunju 27478, Korea. anjhee@hanmail.net.
authors.forename: Jeung Hee
authors.initials: JH
authors.lastname: An
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D000431:Ethanol / Q000633:toxicity*; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494828:Bax protein, rat; D015850:Interleukin-6; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000431:Ethanol; D009828:Oleanolic Acid; D002784:Cholesterol; D000426:Alcohol Dehydrogenase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C025763:hederagenin
keywords: ALDH2; alcohol; apoptosis; hederagenin; inflammatory; liver disease