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

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.

Keywords

• Ormosanine
• Ethanol-induced liver injury
• Inflammation
• Apoptosis
• Antioxidant enzyme