Abstract
Amarogentin, a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots, has been suggested to exhibit many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. The present study was designed to evaluate the protective effects of amarogentin on carbon tetrachloride-induced liver fibrosis in vivo and the underlying mechanism. Fibrosis was induced by subcutaneous injections of 6 mL/kg of 20% carbon tetrachloride (dissolved in olive oil) twice per week for seven weeks. Mice were orally treated with 25, 50, and 100 mg/kg amarogentin and with colchicine as a positive control. Biochemical assays and histopathological investigations showed that amarogentin delayed the formation of liver fibrosis; decreased alanine aminotransferase, aspartate aminotransferase, malondialdehyde and hydroxyproline levels; and increased albumin, cyclic guanosine monophosphate, glutathione peroxidase, and superoxide dismutase levels. Moreover, amarogentin exhibited downregulation of α-smooth muscle actin and transforming growth factor-β1 levels in immunohistochemical and Western blot analyses. The levels of phosphorylated extracellular regulated protein kinases, c-Jun N-terminal kinase, and p38 were also significantly reduced in all amarogentin-treated groups in a dose-dependent manner. These findings demonstrated that amarogentin exerted significant hepatoprotective effects against carbon tetrachloride-induced liver fibrosis in mice and suggested that the effect of amarogentin against liver fibrosis may be by anti-oxidative properties and suppressing the mitogen-activated protein kinase signalling pathway.
Highlights
Liver fibrosis results from a continuous wound-healing response of the liver to repeated injury, such as chronic hepatitis B or C infections, chemical intoxication, alcohol abuse, metabolic syndrome, or autoimmune diseases [1]
hepatic stellate cells (HSCs) proliferation was measured by Cell Counting Kit-8 (CCK-8) assay, and the protein expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 Associated X protein (Bax) were determined by Western blot to
The results showed that there is no significant inhibitory effect of AG on HSC proliferation
Summary
Liver fibrosis results from a continuous wound-healing response of the liver to repeated injury, such as chronic hepatitis B or C infections, chemical intoxication, alcohol abuse, metabolic syndrome, or autoimmune diseases [1]. Chronic liver injury disrupts the balance between the production and degradation of extracellular matrix (ECM) and subsequently leads to liver fibrosis and cirrhosis. Liver injury may develop into hepatic failure or hepatocellular carcinoma (HCC) [2]. Liver fibrosis and cirrhosis remain major causes of morbidity and mortality worldwide and have increasing economic and social impacts [3], but efficient anti-fibrotic drugs with few side effects have not been discovered. The current treatment for hepatic fibrosis is limited to withdrawal of the noxious agents and orthotropic liver transplantation in the late stages.
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