Ramalin, an antioxidant compound derived from Antarctic lichen, prevents progression of liver fibrosis induced by dimethylnitrosamine (DNM) in rats

Biochem Biophys Res Commun. 2018 Sep 26;504(1):25-33. doi: 10.1016/j.bbrc.2018.08.103. Epub 2018 Aug 30.

Abstract

Hepatic fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM), primarily collagen, within the liver. Because reactive oxygen species (ROS) has been implicated in its pathogenesis, the use of antioxidants as a potential treatment has been broadly explored. Here, we investigated the hepatoprotective properties of ramalin (RM), a compound extracted from the Antarctic lichen Ramalina terebrata, against hepatic fibrosis in vitro and in vivo. RM suppressed hepatic stellate cell (HSC) activation in vitro without any significant signs of adverse effects on the cells tested, and the accumulation of ECM was dramatically reduced in the liver tissue. Oral administration of RM in rats noticeably improved the gross appearance of the liver with increased body and liver weight relative to the DMN injected rats, and all of the serum biochemical markers returned to the normal range. RM treatment have ameliorated hepatic fibrosis in rats induced by DMN by repressing α-smooth muscle actin (α-SMA) and upregulating heme oxygenase-1 (HO-1). In addition, RM significantly reduced collagen accumulation, and levels of malondialdehyde (MDA) and hydroxyproline (HP) in the liver tissue of DMN injected rats. The efficacy exerted by RM was through erythroid 2-related factor 2 (Nrf2) mediated antioxidant response proteins such as HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO-1). Our results show the beneficial effect of RM against the progression of hepatic fibrosis.

Keywords: Antarctic lichen extract; Antioxidant; Hepatic fibrosis; Ramalin; Reactive oxigen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use*
  • Cell Line
  • Cell Proliferation / drug effects
  • Dimethylnitrosamine
  • Disease Progression
  • Glutamates / chemistry
  • Glutamates / therapeutic use*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects
  • Humans
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • NF-E2-Related Factor 2 / metabolism
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Rats
  • Response Elements
  • Signal Transduction / drug effects

Substances

  • Antioxidants
  • Glutamates
  • NF-E2-Related Factor 2
  • Platelet-Derived Growth Factor
  • Ramalin
  • Dimethylnitrosamine