Abstract
The current study aimed to investigate the neuroprotective effect of 3-acetyl-11-keto-β-boswellic acid (AKBA) in combination with bioenhancer piperine in lateral fluid percussion injury-induced TBI in experimental rats. Fluid percussion injury was introduced in the rat brain by delivering 50 mmHg of pressure for 3 min to the exposed brain. AKBA 25 mg/kg, 50 mg/kg orally, and AKBA (25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) were administered from day 1 to day 14 to the assigned groups. On the 1st, 7th, and 14th day, behavioral parameters were checked. On the 15th day, animals were euthanized. In TBI rat model, AKBA-piperine combination significantly restored the altered performance of grip strength, rotarod test, open field task, narrow beam task (beam crossing time and no. of foot slips), and Morris water maze (escape latency and time spent in target quadrant) (p < 0.001 vs TBI control). Furthermore, the AKBA-piperine combination significantly reduced pro-inflammatory cytokine level in TBI rat model (&p < 0.001 vs TBI control). The combined effect of AKBA and piperine significantly restored oxidative stress parameters level, catecholamines level, and neurotransmitters level (p < 0.001 vs TBI control). Further findings showed that the AKBA-piperine combination prevented histopathological changes (p < 0.001), and the immunohistological study confirmed increased Nrf2-positive cells (p < 0.001 vs TBI control) and reduced nuclear factor kappa B (NFkB) expression (p < 0.001 vs TBI control, p < 0.01 vs TBI + AKBA 50 mg/kg) in the cortical region following AKBA-piperine administration. The present study concluded that AKBA along with piperine achieved anti-oxidant, and anti-inflammatory effects, and also prevented neuronal injury via targeting Nrf2 and NFkB expressions.
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Abbreviations
- Aβ:
-
Amyloid-β
- AKBA:
-
3-Acetyl-11-keto-β-boswellic acid
- ARE:
-
Antioxidant response elements
- BBB:
-
Blood-brain barrier
- ELISA:
-
Enzyme-linked immune sorbent assay
- FPI:
-
Fluid percussion model
- GABA:
-
Gamma-aminobutyric acid
- HO-1:
-
Heme oxygenase-1
- IL-1β:
-
Interleukin 1 beta
- IL-6:
-
Interleukin 6
- Keap1:
-
Kelch-like ECH-associated protein 1
- MDA:
-
Malondialdehyde
- NF-κB:
-
Nuclear factor-kappa B
- Nrf2:
-
Nuclear factor erythroid-2-related factor 2
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TBI:
-
Traumatic brain injury
- TNF-α:
-
Tumor necrosis factor alpha
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Acknowledgements
The authors express their gratitude to Prof. Y.K. Gupta, President AIIMs Bhopal and AIIMs Jammu and Chairman, and Mr. Parveen Garg, ISF College of Pharmacy, Moga (Punjab), India, for their excellent vision and support.
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Satyabrata Kundu: literature survey, data collection, manuscript writing, preliminary reading; Shamsher Singh: study concept, data analysis, final reading, and approval.
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Kundu, S., Singh, S. Protective Mechanisms of 3-Acetyl-11-keto-β-Boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury Targeting Nrf2 and NFkB Signaling. Neurotox Res 41, 57–84 (2023). https://doi.org/10.1007/s12640-022-00628-x
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DOI: https://doi.org/10.1007/s12640-022-00628-x