Abstract
Vascular dementia (VaD) is associated with the loss of cognitive function. The pharmacotherapy for dementia is cholinesterase inhibitor (ChEI). However, currently available ChEIs produce side effects. Therefore, new anticholinesterase agents are required for treating dementia. In vitro assays showed that Syzygium polyanthum leaf extract (SPLE) inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. Here, we evaluated the nootropic effect of SPLE, mediated via a cholinergic system with long-term hippocampal plasticity (LTP) in chronic cerebral hypoperfusion (CCH) rats. Male Sprague Dawley (SD) rats were subjected to permanent bilateral occlusion of common carotid arteries (POBCCA) or sham groups. An automated open field test (AOFT) was conducted to examine motor and exploratory functions. Cognitive functions were evaluated using Novel object recognition (NOR) and Morris water maze (MWM) tests. At the end of the behavioral task, the brain was harvested to determine cholinesterase, choline acetyltransferase (ChAT), acetylcholine (ACh), and brain-derived neurotrophic factor (BDNF) activities. Hippocampal synaptic plasticity was measured under urethane anesthetized rats. The study revealed SPLE (100, 200, and 300 mg/kg) (i) improved both non-spatial and spatial memories in NOR and MWM tests, respectively; (ii) promoted long-lasting LTP enhancement in CA3-CA1 synapses; (iii) increased the ACh, ChAT and BDNF activities in the frontal cortex, hippocampus and cerebral cortex. Interestingly, the elevated AChE activity in the hippocampus was significantly inhibited by SPLE extract. SPLE executes its cognitive functions by restoration of the cholinergic system. The findings support the therapeutic potential of SPLE in the treatment of VaD.
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This work was supported by the [USM RU TOP-DOWN] (1001/PHARMACY/870031) and [USM RUI] (1001/CDADAH/8012302).
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Kesevan Rajah Kumaran has no conflict of interest. Habibah A. Wahab has no conflict of interest. Zurina Hassan has no conflict of interest.
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Kumaran, K.R., Wahab, H.A. & Hassan, Z. Nootropic effect of Syzygium polyanthum (Wight) Walp leaf extract in chronic cerebral hypoperfusion rat model via cholinergic restoration: a potential therapeutic agent for dementia. ADV TRADIT MED (ADTM) 23, 833–850 (2023). https://doi.org/10.1007/s13596-022-00653-3
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DOI: https://doi.org/10.1007/s13596-022-00653-3