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