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

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

Author information

1
Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Egypt. Electronic address: ayman.mahmoud@science.bsu.edu.eg.
2
Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Egypt.
3
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Beni-Sueif University, Egypt.
4
Department of Pharmacology, Faculty of Medicine, Beni-Suef University, Egypt.

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

PMID:
28414157
DOI:
10.1016/j.cbi.2017.04.012
[Indexed for MEDLINE]

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