Commiphora molmol resin attenuates diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis and Nrf2/ARE/HO-1 signaling

Chem Biol Interact. 2017 May 25;270:41-50. doi: 10.1016/j.cbi.2017.04.012. Epub 2017 Apr 14.

Abstract

The objective of the current study was to investigate the possible chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using DEN for initiation and PB as a promoting agent. The rats received 125 or 250 mg/kg C. molmol resin extract throughout the experiment. Both doses of myrrh improved liver function marker enzymes and prevented oval cells proliferation and the distortion of hepatic architecture. The pro-inflammatory cytokine interleukin-6, tumor markers, angiogenesis markers, lipid peroxidation and nitric oxide (NO) were significantly increased in DEN/PB-induced rats. In addition, the antioxidant defenses showed marked reduction in the liver of DEN/PB-induced rats. Oral administration of C. molmol extract to DEN/PB-induced rats significantly decreased circulating markers of inflammation, tumor proliferation and angiogenesis, and liver lipid peroxidation and NO. In addition, C. molmol markedly ameliorated the antioxidant defenses and up-regulated Nrf2 and hemeoxygenase (HO)-1 in the liver of DEN/PB-induced rats. In conclusion, these results provide evidence that C. molmol resin has a potent chemopreventive activity, possibly by up-regulating the Nrf2/HO-1 signaling and attenuation of inflammation, angiogenesis and oxidative stress.

Keywords: Carcinogenesis; Inflammation; Myrrh; Nrf2; Oxidative stress.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Diethylnitrosamine / toxicity
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism
  • Inflammation / drug therapy
  • Liver / cytology
  • Liver / drug effects
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Oxidative Stress / drug effects*
  • Phenobarbital / toxicity
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Terpenes / pharmacology*
  • Terpenes / therapeutic use*
  • Vesicular Transport Proteins / metabolism

Substances

  • NF-E2-Related Factor 2
  • Terpenes
  • Vesicular Transport Proteins
  • Diethylnitrosamine
  • Heme Oxygenase-1
  • myrrh oil
  • Phenobarbital