Abstract
Forsythia Fruit (FF), the fruit of Forsythia suspensa, has been used since ancient times as an herbal medication in East Asia to treat inflammation, gonorrhea, and pharyngitis. However, the efficacy of FF against liver damage due to inflammation has not been studied. Here, we explored the protective effects of FF in a mouse hepatitis model induced by lipopolysaccharide (LPS)/D-galactosamine (GalN) treatment. We measured inflammatory cytokine and aminotransferase levels in mouse blood and analyzed the effects of FF on inflammatory gene and protein expression levels in liver tissue. Our results show that FF treatment effectively lowers inflammatory cytokine and serum aminotransferase levels in mice and inhibits the expression of hepatic cytokine mRNA and inflammatory proteins. Furthermore, treatment with FF activated the antioxidant pathway HO-1/Nrf-2 and suppressed severe histological alteration in the livers of LPS/D-GalN-treated mice. Further investigation of the effects of FF on inflammatory reactions in LPS-stimulated macrophages showed that pretreatment with FF inhibits inflammatory mediator secretion and activation of inflammatory mechanisms both in a mouse macrophage RAW 264.7 cells and in primary peritoneal macrophages. These results show that FF has potential worth as a candidate for the treatment of fulminant inflammatory reactions and subsequent liver injury.
Highlights
Fulminant liver injury is characterized by rapid, widespread liver dysfunction and can result in encephalopathy, jaundice, and severe coagulopathy [1,2]
LPS plays a critical role in the early stage of endotoxic damage, increases inflammatory cytokine levels, and damages liver tissue, so we explored the inhibitory activities of Forsythia Fruit (FF) on inflammatory cytokine levels in mouse serum
High concentrations of aminotransferase are present in the liver and heart, and when liver parenchymal cells are damaged, ALT, AST, and alkaline phosphatase (ALP) in the cytoplasm are released into the blood [27], so activity of these enzymes is an important indicator of liver injury
Summary
Fulminant liver injury is characterized by rapid, widespread liver dysfunction and can result in encephalopathy, jaundice, and severe coagulopathy [1,2]. It is a clinical manifestation of sudden and severe hepatic failure, which is difficult to prevent and treat, resulting in poor prognosis and a high mortality rate [3]. D-GalN induces changes in colorectal mucosal permeability, increasing endotoxin absorption, which interferes with the ability of liver cells to repair membranes and causes hepatic toxicity [8]. D-GalN causes necrosis of the liver during acute exposure and cirrhosis of the liver and cellular tumors during chronic exposure [9,10]
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