Abstract
Stroke is considered one of the leading causes of death worldwide. The treatment is limited; however, the Brazilian flora has a great source of natural products with therapeutic potentials. Studies with the medicinal plant Polygala sabulosa W. Bennett provided evidence for its use as an anti-inflammatory and neuroprotective drug. In the case of ischemic stroke due to lack of oxygen, both acute and chronic inflammatory processes are activated. Thus, we hypothesized that P. sabulosa (HEPs) has the potential to treat the motor and cognitive deficits generated by ischemic stroke. Male mice were subjected to global ischemia for 60 min, followed by reperfusion and orally treated with HEPs (100 mg/kg in saline + 3% tween 20) twice a day (12 h apart) for 48 h starting 3 h after surgery. Motor skills were assessed using grip force and open field tasks. Hippocampi were then collected for mRNA quantification of the cytokines IL-1-β and TNF-α levels. After 48 h of acute treatment, spatial reference memory was evaluated in a Morris water maze test for another group of animals. We show that HEPs treatment significantly prevented motor weakness induced by ischemia. Brain infarct area was reduced by 22.25% with downregulation of the levels of IL-1β and TNF-α mRNA. Learning performance and memory ability on Morris water maze task were similar to the sham group. Our data demonstrates the neuroprotective properties of HEPs through its anti-inflammatory activities, which prevent motor and cognitive impairments, suggesting that HEPs may be an effective therapy for ischemic stroke.
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Abbreviations
- BBB:
-
blood-brain barrier
- HEPs:
-
hydroalcoholic extract from Polygala sabulosa Polygala sabulosa
- BCCAo:
-
bilateral common carotid artery occlusion
- MWM:
-
morris water maze
- TTC:
-
2,3,5-triphenyl tetrazolium chloride
- NMDA:
-
N-methyl-D-aspartate
- AMPA:
-
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- TNF-α:
-
Tumor necrosis factor alpha
- IL:
-
interleukin
- OFT:
-
open field test
- GFT:
-
grip force test
- O + V:
-
animals submitted to ischemic surgery treated with vehicle
- S + V:
-
animals submitted to sham surgery and treated with vehicle
- S + HEPs:
-
animals submitted to sham surgery and treated with HEPs
- O + HEPs:
-
animals submitted to ischemic surgery and treated with HEPs
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Acknowledgements
The authors thank the Health Sciences Center facilities Laboratório de Análises Biomoleculares (LABIOM) and Histologia e Imunoistoquímica (LHMI). The authors are indebted to Dr. Iaci Nunes for editing the manuscript, Dr. Roger J. Thompson, Dr. Andrew Boyce and Dr. Adam Institoris (University of Calgary, Hotchkiss Brain Institute) for critically reading the manuscript. Adair R.S. Santos is the recipient of a research productivity fellowship from the CNPq (grant number 311715/2018-4).
Funding
This work was supported by Fundação de Amparo à Pesquisa do Espírito Santo (FAPES), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), and Programa INCT-INOVAMED (grant 465430/2014-7), Brazil.
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NSP, GGF, and RMA performed the experiments; TAA was responsible for behavioral analysis; RGWP supported the behavioral tests; TT and MGP were responsible for HEPs production; CMS wrote the manuscript and was responsible for qPCR experiments, and the study’s concept and design. ARSS wrote and provided essential critical analysis of the manuscript.
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Martins-Silva, C., de Souza Pinho, N., Ferreira, G.G. et al. Polygala sabulosa A.W. Bennett extract mitigates motor and cognitive deficits in a mouse model of acute ischemia. Metab Brain Dis 36, 453–462 (2021). https://doi.org/10.1007/s11011-020-00660-w
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DOI: https://doi.org/10.1007/s11011-020-00660-w