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

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.