2026 ECNP Congress

PS03-3015

Fimasartan ameliorates cognitive impairment in a scopolamine-induced Alzheimer’s disease model in rats

Fadime Topal — S. Aydin, E. Sarman, B. Ertas, J. Akgol · Afyonkarahisar Health Science University, Faculty of Medicine- Department of Medical Pharmacology, Afyonkarahisar, Türkiye

2026 ECNP Congress

Background:

Alzheimer’s disease (AD) is a progressive and multifactorial neurodegenerative disorder characterized by amyloid-β accumulation, tau pathology, oxidative stress, and neuroinflammation [1]. Currently available treatments provide only symptomatic treatment and do not prevent disease progression, highlighting the need for novel therapeutic strategies. Increasing evidence suggests that the renin–angiotensin system may contribute to AD pathology through its effects on cerebral blood flow, oxidative balance, and inflammatory processes [2]. Fimasartan is a novel angiotensin II type 1 receptor blocker [3]. This study aimed to evaluate the potential effects of fimasartan in a scopolamine-induced rat model of AD.

Methods:

Adult Wistar albino rats were randomly divided into seven groups (n = 6 per group): control, scopolamine (SCP), donepezil (DO), Fimasartan (FS), SCP+DO, SCP+FS, and vehicle. Scopolamine (1 mg/kg, i.p.) was administered for 24 days to induce cognitive impairment. Donepezil (10 mg/kg, p.o.) and FS (1 mg/kg, p.o.) were administered via oral gavage for the same duration. Cognitive performance was evaluated using the Novel Object Recognition Test, Passive Avoidance Test, and Morris Water Maze. For histopathological evaluation, brain tissues collected on day 24 were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 µm, and stained with hematoxylin–eosin. Sections from the prefrontal cortex and hippocampus were examined for hyperemia, perivascular edema, extracellular vacuolization, gliosis, and neuronal degeneration, which were semi-quantitatively graded (0–3) [4]. Cellular viability was assessed using the MTT assay.

Results:

SCP administration impaired cognitive performance across the Passive Avoidance Test and Morris Water Maze. In the SCP+FS group, the administered treatment improved cognitive impairment, retention latency, and spatial learning compared to the SCP group. This level of improvement was also found to be comparable to the effects observed in the SCP+DO group. The Novel Object Recognition Test data demonstrated that the recognition memory performance observed in the treatment group was significantly improved compared to the scopolamine group and approached that of the control group.

MTT analysis indicated that the reduction in cell viability observed in the SCP group was attenuated in FS-treated animals. Histopathological examination showed that the control, vehicle, FS, and DO groups largely preserved normal brain architecture. In contrast, the SCP group exhibited neuronal degeneration, extracellular vacuolization, hyperemia, and perivascular edema in the prefrontal cortex and hippocampus. These alterations appeared to be reduced in the SCP+DO and SCP+FS groups, with lower levels of neuronal degeneration, gliosis, and vascular congestion, while hyperemia and perivascular edema were observed at milder levels.

Conclusion:

FS treatment was associated with improvements in cognitive performance, cellular viability, and histopathological alterations in a scopolamine-induced model of AD. These findings suggest that modulation of the renin–angiotensin system may have a role in AD pathophysiology, and that FS could represent a potential therapeutic candidate. However, further experimental and clinical studies are needed to clarify its effects and underlying mechanisms.

References

  1. Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024). Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline. ACS chemical neuroscience, 15(21), 3800–3827.
  2. Loera-Valencia, R., Eroli, F., Garcia-Ptacek, S., and Maioli, S. (2021). Brain Renin-Angiotensin System as Novel and Potential Therapeutic Target for Alzheimer’s Disease. International journal of molecular sciences, 22(18), 10139.
  3. Kim, C. K., Yang, X. L., Kim, Y. J., Choi, I. Y., Jeong, H. G., Park, H. K., Kim, D., Kim, T. J., Jang, H., Ko, S. B., & Yoon, B. W. (2015). Effect of Long-Term Treatment with Fimasartan on Transient Focal Ischemia in Rat Brain. BioMed Research International, 295925.
  4. Tepebası M.Y., Ascı H., Kosar P.A., Dincer, E.N., Selcuk,E., Kolay, O., Huseynov, I. (2015). Potential Ameliorating Effects of Fluvoxamine in a Rat Model of Endotoxin-Induced Neuroinflammation: Molecular Aspects Through SIRT-1/GPX-4 and HMGB-1 Signaling. Mol Neurobiol. ;62(6):7892-7902.