Hepatoprotective effects of brown algae Sargassum boveanum on bile duct-ligated cholestasis in rats are mediated by modulating NF-κB/TNF-α and Nrf۲/HO-۱ gene expression

Objective: The current study assessed hepatoprotective effects of Sargassum boveanum (S. boveanum) in cholestatic rats. To induce cholestasis, bile duct ligation (BDL) was utilized.Materials and Methods: Five groups of Sprague-Dawley rats including Sham and four BDL groups were assigned to receive vehicle (BDL-V) or ethanolic extract of S. boveanum at ۱۰۰ (BDL-SE ۱۰۰), ۲۰۰ (BDL-SE ۲۰۰) and ۵۰۰ (BDL-SE ۵۰۰) mg/kg/day for seven days.Results: BDL group receiving the vehicle (BDL-V) had substantially increased blood levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total, and indirect bilirubin in comparison to the sham group. S. boveanum significantly decreased these variables compared to the BDL-V group. Hepatic malondialdehyde and tumor necrosis factor-α (TNF-α) level, and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and TNF-α gene expression were higher in BDL-V rats compared to the sham group but these were reduced markedly in BDL groups receiving S. boveanum in comparison to the BDL-V group. BDL-V group had a significantly lower hepatic glutathione value, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity and gene expression of SOD, GPx, Nrf۲, HO-۱ in comparison to the sham group. S. boveanum prevented the decrease of these variables. The histopathological assay showed marked bile ducts proliferation, portal inflammation, and hepatocellular damage in the BDL-V group and S. boveanum administration remarkably reduced hepatic injury. Gas chromatography-mass spectroscopy (GC-MS) analysis revealed that S. boveanum ethanolic extract contained ۳۹ active compounds.Conclusion: S. boveanum treatment significantly ameliorated cholestatic hepatic injury via anti-oxidative and anti-inflammatory effects.