Molecular Targeting of Nrf2 and NFkB Signaling by 3-acetyl-11-keto- β-boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury

Abstract

\n Background & purpose: Traumatic brain injury in rats through lateral fluid percussion injury (LFPI) causes elevation in intracranial pressure which leads to impairments in motor and cognitive behavior. 3-acetyl-11-keto-β-boswellic acid (AKBA) is a well-known anti-inflammatory agent but it has very low bioavailability. The current study was established to investigate the neuroprotective effect of AKBA in combination with bioenhancer piperine in LFPI induced TBI experimental rats.Experimental approach: Fluid percussion injury was created by delivering 50 mmHg of pressure for 3 minutes to the exposed brain. AKBA 25 mg/kg and 50 mg/kg orally and AKBA ((25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) was administered from day 1 to day 14. On 1st, 7th and 14th day, the behavioral parameters were checked. On 15th day, animals were euthanized. Then the cortex was isolated for the estimation of biochemical levels (MDA, nitrite, reduced GSH, catalase), neuroinflammatory markers (TNF-α, IL-1β, IL-6), and neurotransmitters (norepinephrine, dopamine, 5-HT, GABA, glutamate). From some animals, hippocampus and cortex were isolated for histopathological analysis and expressions of Nrf2 and NFkB was measured by immunohistological study. Key results: Treatment with AKBA significantly attenuated LFPI induced abnormalities, biochemical and neurotransmitter changes in experimental rats. Further finding AKBA in combination with piperine significantly prevented histopathological changes, increased Nrf2 positive cells and reduced NFkB expression in the cortical region. Conclusion & implication: The present study concluded that AKBA along with piperine achieved anti-oxidant, anti-inflammatory, neuromodulatory effects as well as prevented neuronal injury via targeting Nrf2 and NFkB.