Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning. Orthosiphon stamineus (OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties whereby in vitro studies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kg via oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.
Highlights
Neurodegenerative diseases have emerged to become a globally critical burden with the aging population
These results demonstrate that supplementation of Orthosiphon stamineus (OS) extract significantly improved memory function in rats demonstrating optimal nootropic effects
The rats that were treated with 50 mg/kg OS extract showed a decrease in transfer latency in which the rats were able to remember and enter the closed arm quickly compared to the training session, which was observable by the improved inflexion ratio, the rats that were treated with 200 mg/kg did show improved memory retention as compared to the scopolamine treated group but not as that observed in the 50 mg/kg OS treated group
Summary
Neurodegenerative diseases have emerged to become a globally critical burden with the aging population. Alzheimer’s disease (AD) is the most common cause of cognitive impairment in the elderly population and is characterized by various symptoms that include learning and memory impairment, cognitive dysfunction, language impairment and behavioral dysfunction like depression, agitation and psychosis that continue to become more severe with the disease progression (Brookmeyer et al, 2007; Mahdy et al, 2012). Four cholinesterase inhibitors or ChEI (tacrine, rivastigmine, donepezil and galantamine) and a partial NMDA receptor antagonist (memantine) are the only approved treatment options for AD These drugs fail to completely cure the disease, which warrants a search for newer class of targets that would eventually lead to effective drugs for the treatment of AD (Obulesu and Rao, 2011). Major therapeutic research is underway to explore the memory enhancing activities of natural products
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