Ormosanine from Akebia quinata suppresses ethanol-induced inflammation and apoptosis and activates antioxidants via the mitogen activated protein kinase signaling pathway. (September 2018)

• Record Type: Journal Article
• Authors: Song, Da Hye; Kim, Gyeong-Ji; Chung, Kang-Hyun; Lee, Kwon Jai; An, Jeung Hee
• Is Part Of: Journal of functional foods. Volume 48(2018)
• Page Start: 357
• Page End: 366
• Publication Date: 2018-09
• Subjects: Ormosanine -- Ethanol-induced liver injury -- Inflammation -- Apoptosis -- Antioxidant enzyme; ABTS 2, 2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) -- AQ Akebia quinata -- AST alanine aminotransferase -- ALD alcoholic liver disease -- Bcl-2 B-cell lymphoma 2 -- Bax Bcl-2-associated X protein -- CYP2E1 cytochrome P450 2E1 -- FAB-MS fast atom bombardment mass spectrometry -- GST glutathione S-transferase -- HPLC high-performance liquid chromatography -- p-AKT phosphorylated-AKT -- p-ERK phosphorylated-ERK -- p-JNK phosphorylated-JNK -- PARP-1 poly[ADP-ribose] polymerase 1 -- RT reactive oxygen species (ROS) retention time -- ALT serum aspartate alanine aminotransferase -- TG serum triglyceride -- SOD-1 superoxide dismutase -- TLC thin layer chromatography -- TC total cholesterol -- p53 tumor protein p53; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2018.07.033
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: In this study, we evaluated whether ormosanine from AQ exhibited antioxidant, anti-inflammatory, or anti-apoptotic effects in a rat model of ethanol-induced liver injury. The protective activities of ormosanine against ethanol toxicity in the liver include the suppression of acetaldehyde through activation of ALDH2 and suppression of CYP2E1. Our study shows that ormosanine protects against ethanol-induced liver injury by reducing the expression of inflammatory regulators (COX-2, TNF-α, and IL-6), and apoptosis-associated protein (p53, Bax, cytochrome C, procaspase-3, PARP-1) via activating the p-AKT and MAPK (p-ERK, and p-JNK) signaling pathways. Therefore, ormosanine plays an important role as a free radical-scavenger and may help prevent as well as alleviate ethanol-induced liver injury. Highlights: This is the first report of ormosanine isolated from Akebia quinata . Ormosanine increases anti-inflammation capacity in ethanol-induced liver. Ormosanine alleviates ethanol-induced liver injury by reducing oxidative stress. Ormosanine decreases apoptosis signaling induced by ethanol administration. Abstract: We investigated the hepatoprotective, anti-inflammatory, anti-apoptosis, and antioxidant effects of ormosanine from Akebia quinata in a rat model of ethanol-induced liver injury. Ormosanine was identified and isolated by high-performance liquid chromatography and fast atom bombardment mass spectrometry. Oral administration of ormosanine significantly reduced the serum and liver levels of liver injury markers (alanine aminotransferase, aspartate aminotransferase, total cholesterol, and triglyceride). In addition, ormosanine significantly inhibited ethanol-induced cytochrome P450 2E1 activation and upregulated the levels of ALDH2 . Ormosanine suppressed pro-inflammatory cytokines (tumor necrosis factor-alpha, cyclooxygenase-2, and interleukin-6) and downregulated apoptosis-related proteins (p53, cytochrome C, procaspase-3, poly[ADP-ribose] polymerase 1) by upregulating the phosphorylated-AKT, JNK, and extracellular signal regulated kinase pathways. Ormosanine exhibited antioxidant activity by upregulating superoxide dismutase, glutathione S-transferase, and B-cell lymphoma 2. Therefore, ormosanine plays an important role as a free radical-scavenger and may help prevent as well as alleviate ethanol-induced liver injury.