Huperzine A protects against traumatic brain injury through anti-oxidative effects via the Nrf2-ARE pathway

Document Type : Original Article


1 Department of Pharmacy, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guang-zhou Medical University, Guangzhou, Guangdong Province, 510150, P.R. China

2 Guangzhou Medical University, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510150, P.R. China

3 Department of Pharmacy, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, 510150, P.R. China


Objective(s): Traumatic brain injury (TBI) is a prominent health problem worldwide and it may lead to cognitive dysfunction, disability, and even death. To date, there is no effective treatment for TBI.  Our previous study showed that Huperzine A (HupA) improved cognitive function in a mouse model of TBI. However, the detailed mechanism of HupA remains unaddressed. In this study, we investigated the possible mechanism of the neuroprotective effect of HupA. 
Materials and Methods: C57BL/6 mice were randomly divided into 3 groups as sham, injured with vehicle treatment, and injured with HupA treatment groups. The Morris water maze task was used to evaluate the impairment of special learning and memory. Brain edema was as-sessed by measuring the wet weight to dry weight ratio. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were measured for oxidative stress. Protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygen-ase-1(HO-1), and synaptophysin were detected by Western blot. The brain sections were stained with hematoxylin-eosin (H&E) for histology study.
Results: We found that HupA therapy improved histology and cognitive functional outcomes after TBI. HupA reduced brain edema in TBI mice. furthermore, HupA inhibited ox-idative stress. HupA promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nu-clear translocation and activated Nrf2 after TBI. 
Conclusion: HupA protects against TBI through antioxidative effects via the Nrf2-ARE pathway.


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