The Protective Effect of Esculentoside A on Experimental Acute Liver Injury in Mice

Abstract

Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl4) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl4 and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-α and cell death rate challenged by CCl4. Moreover, EsA treatment up-regulated PPAR-γ expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl4. In vivo, EsA prevented mice from CCl4-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-α, Interleukin (IL)-1β and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl4-induced phosphonated IkBalpha (P-IκB) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl4-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl4 and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-γ, NF-κB and ERK signal pathways.

Suppressive Effect of Kampo Formula “Juzen-taiho-to” on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

“…9) Several studies have shown how some compounds show protective effects against CCl 4 -induced hepatotoxicity. [7][8][9][10] Some of these compounds attenuated oxidative stress and the inflammatory response. 10) As JTX modulates the immune system, such as Toll-like receptor 4 signaling pathways, 25,26) it might also suppress the inflammatory response activated by CCl 4 .…”

“…In addition, associated protective mechanisms possibly act on each of the five steps. [7][8][9][10] The Japanese herbal medicine "Juzen-taiho-to" (JTX) is a Kampo medicinal prescription, and has been used historically in Japan for the treatment of cancers, rheumatoid arthritis, and atopic dermatitis. 11) JTX is consisting of ten medicinal herbs in the indicated amounts (g per day in human intake);…”

Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate

“…Several studies have shown some compounds show protective effects against CCl 4 -induced hepatotoxicity (Singh et al, 2008;Huang et al, 2012;Ma et al, 2014;Zhang et al, 2014). These investigations focused primarily on blood levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (markers of liver damage), histological evaluation, lipid peroxidation, and expression levels of cytochromes P450.…”

Kampo formula “Hochu-ekki-to” suppressed carbon tetrachloride-induced hepatotoxicity in mice

“…Through these steps, necrosis is induced; this induction is termed as the fifth step. Multiple compounds have been reported to show protective effects against CCl 4 -induced hepatotoxicity, and associated protective mechanisms have been proposed to act on each of the five steps [7][8][9][10].…”