Hepatoprotective effect of Commiphora myrrha against D-GalN/LPS-induced hepatic injury in a rat model through attenuation of pro inflammatory cytokines and related genes

Abstract

Context: Commiphora myrrha (Burseraceae), a shrub resembling a small tree, has been used for several centuries for the treatment of various diseases. Objective: This study investigates the hepatoprotective activity of C. myrrha ethanol extract against D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced acute hepatic injury in an animal model. Materials and methods: Rats were pretreated with ethanolic extract C. myrrha (250 and 500 mg/kg; p.o.) for 7 d prior to the induction of an acute phase response by D-GalN/LPS. Animals were sacrificed 24 h after D-GalN/LPS (800 mg/kg and 50 μg/kg i.p.) administration for the biochemical and histological analyses. Results: The administration of D-GalN/LPS increased plasma aminotransferases (174.47 ± 4.5761 and 260.96 ± 1.9839 μkat/l) and total bilirubin levels (1.012 ± 0.0288 mg/dl), which were attenuated by C. myrrha treatment. Hepatic lipid peroxidation activity and nitric oxide content also increased, while the antioxidant activity measured by GSH (0.76 nmol/g protein), SOD (81.91 U/mg protein), and CAT (15.78 U/mg protein) was reduced. Commiphora myrrha provided significant restoration of GSH (0.815 nmol/gm protein), SOD (140.57 U/mg protein), and CAT (27.02 U/mg protein) levels. Furthermore, the acute phase response elicited by D-GalN/LPS administration enhanced mRNA expressions of TNF-α, IL-6, IL-10, iNOS-2, and HO-1, which were ameliorated by C. myrrha treatment. Discussion and conclusion: These findings indicate that C. myrrha considerably reduces the oxidative stress of D-GalN/LPS-induced hepatic injury via multiple pathways including adown regulation of inflammatory mediators and cytokines. Such a property might be sufficient to combat cellular damage caused by various conditions that resemble fulminant hepatitis and could be of a potential clinical application.