Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 74, Issue 12, Pages 1765-1775Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgac071
Keywords
acute liver injury; bromelain; D-galactosamine; Nrf2; silymarin; SIRT1; AMPK
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This study demonstrated the significant hepatoprotective effects of bromelain against D-galactosamine-induced acute liver injury, with potential mechanisms involving modulation of SIRT1/LKB1/AMPK, GSK3 beta/Nrf2 signaling, as well as NF-kappa B p65/TNF-alpha/caspase-8 and caspase-9 pathways.
Objectives The present research focused on estimating, for the first time, the potential protective effects of bromelain against D-galactosamine-induced acute liver injury in rats as well as identifying the possible underlying mechanisms. Methods Silymarin (100 mg/kg/day, p.o.) as a reference drug or bromelain (20 and 40 mg/kg/day, p.o.) were administered for 10 days, and on the 8th day of the experiment, a single dose of galactosamine (400 mg/kg/i.p.) induced acute liver injury. Key findings Pretreatment with bromelain improved liver functions and histopathological alterations induced by galactosamine. Bromelain ameliorated oxidative stress by inducing SIRT1 protein expression and increasing LKB1 content. This resulted in phosphorylating the AMPK/GSK3 beta axis, which stimulated Nrf2 activation in hepatic cells and thus increased the activity of its downstream antioxidant enzymes [HO-1 and NQO1]. Besides, bromelain exerted significant anti-apoptotic and anti-inflammatory effects by suppressing hepatic contents of TNF-alpha, NF-kappa B p65, as well as caspase-8 and caspase-9. The protective effects of bromelain(40) were proved to be better than silymarin and bromelain(20) in most of the assessed parameters. Conclusions Our results highlight the significant hepatoprotective effects of bromelain against acute liver injury through modulation of SIRT1/LKB1/AMPK, GSK3 beta/Nrf2 signalling in addition to NF-kappa B p65/TNF-alpha/ caspase-8 and -9 pathway.
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