Hepatoprotective effects of norgalanthamine on carbon tetrachloride induced-hepatotoxicity in mice

Norgalanthamine is a major component of Crinum asiaticum var. japonicum that exhibits several biological activities. This study evaluated the anti-inflammatory and anti-oxidative properties of norgalanthamine in mice with carbon tetrachloride (CCl₄)-induced liver injury. Norgalanthamine (1 and 10 mg/kg) was orally administered to mice for 7 or 14 days, after which liver injury was induced by CCl₄ (1.5 ml/kg, i.p.). The vehicle and positive controls consisted of phosphate-buffered saline and silymarin (100 mg/kg), respectively. In CCl₄-injured mice, norgalanthamine pretreatment significantly reversed the increases in serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels, and the decrease in the serum glucose level. In the liver, norgalanthamine restored the activities of the antioxidant enzymes superoxide dismutase and catalase, while reducing lipid accumulation and, concurrently, the expression of genes involved in lipid synthesis, including peroxisome proliferator-activated receptor γ and adipocyte protein-2. Norgalanthamine also ameliorated inflammation by down-regulating the expression of the pro-inflammatory mediators, TNF-α, IL-1β, and MCP-1, and up-regulating the Nrf2/HO-1 pathway. In addition, norgalanthamine decreased collagen deposition in liver tissue as shown on picrosirius red staining by down-regulating expression of the fibrosis-related genes αSMA and fibronectin. Collectively, these findings imply that norgalanthamine mitigates CCl₄-induced hepatic injury by increasing anti-oxidative activity, down-regulating pro-inflammatory mediators and fibrosis-related genes in the liver.HighlightsNorgalanthamine ameliorated the hepatotoxicity after CCl₄ injury.Norgalanthamine suppressed the activation of Kupffer cells and macrophages.Norgalanthamine down-regulated pro-inflammatory mediators.Norgalanthamine increased anti-oxidative activity via the Nrf2/HO-1 pathway.Norgalanthamine downregulated fibrosis-related genes in the liver.