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Molecules 2017, 22(5), 754; doi:10.3390/molecules22050754

Protective Effects of Amarogentin against Carbon Tetrachloride-Induced Liver Fibrosis in Mice

1
Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi’an 710032, China
2
Xi’an Day Natural Inc., F501 Gazelle Valley, Pioneering R&D Park, 69 Jinye Road, Xi’an 710077, China
*
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 14 March 2017 / Revised: 30 April 2017 / Accepted: 1 May 2017 / Published: 6 May 2017
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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. View Full-Text
Keywords: amarogentin; carbon tetrachloride; liver fibrosis; α-smooth muscle actin; mitogen-activated protein kinase amarogentin; carbon tetrachloride; liver fibrosis; α-smooth muscle actin; mitogen-activated protein kinase
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MDPI and ACS Style

Zhang, Y.; Zhao, H.; Li, H.; Cao, W.; Wang, F.; Zhang, T.; Wang, S.-W. Protective Effects of Amarogentin against Carbon Tetrachloride-Induced Liver Fibrosis in Mice. Molecules 2017, 22, 754.

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