Glioprotective Effect of Chitosan-Coated Rosmarinic Acid Nanoemulsions Against Lipopolysaccharide-Induced Inflammation and Oxidative Stress in Rat Astrocyte Primary Cultures

  • Flávia Nathiely Silveira FachelEmail author
  • Morgana Dal Prá
  • Juliana Hofstätter Azambuja
  • Marcelo Endres
  • Valquíria Linck Bassani
  • Letícia Scherer Koester
  • Amelia Teresinha Henriques
  • Alethea Gatto Barschak
  • Helder Ferreira Teixeira
  • Elizandra Braganhol
Original Research


Rosmarinic acid (RA) is a natural polyphenolic compound with a well-documented neuroprotective effect mainly associated with its anti-inflammatory and antioxidant activities. Recently, our research group developed and optimized chitosan-coated RA nanoemulsions (RA CNE) intended to be used for nasal delivery as a new potential neuroprotective therapy. In this sense, the present study aimed to evaluate the protective and/or therapeutic potential of RA CNE in inflammation/oxidative stress induced by LPS (1 μg mL−1) in rat astrocyte primary cultures. In summary, pre-treatment with RA CNE before exposure to LPS (protective protocol) reduced significantly the LPS-induced alterations in astrocyte cell viability, proliferation, and cell death by necrosis, which was not observed in therapeutic protocol. RA CNE protective protocol also enhanced anti-oxidative status by ~ 50% by decreasing oxygen reactive species production and nitric oxide levels and preventing total thiol content decrease. Finally, our results demonstrate the protective effect of RA CNE in migratory activation and GFAP expression of reactive astrocytes. Overall, our findings indicate for the first time the RA CNE glioprotective potential, associated with an increase in cell viability and proliferation, a preventive effect on cellular death by necrosis, migratory ability and hypertrophic reactive astrocytes, and the reparation of astrocyte redox state.

Graphical Abstract


Rosmarinic acid Chitosan-coated nanoemulsions Lipopolysaccharide Astrocytes Glioprotective effect 



The authors are gratefully acknowledged to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—processos 459619/2014-4; 310846/2014-5; 422298/2016-6), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS—processos 16/2551-0000265-7; 16/2551-0000473-0; 17/2551–0001273-9), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES—Finance Code 001) for the financial grants. F.N.S.F. and J.H.A. would like to thank CAPES, CNPq (GD processo 142202/2018-5), and UFCSPA for the doctoral Grant. V.L.B., L.S.K., A.T.H., E.B., and H.F.T. are recipients of CNPq research fellowship.

Author Contributions

FNSF, MDP, JHA, and ME performed the experiments, acquisition of data, analysis and interpretation of data, and wrote the paper. VLB, LSK, ATH, AGB, HFT, and EB made substantial contributions to the conception and design of the study, and critically revised the manuscript. All authors were involved in drafting the manuscript it critically for important intellectual content. All authors gave final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with Ethical Standards

Conflicts of interest

The authors declare no conflict of interest.

Ethical Approval

All experiments described in this paper were approved by the Ethics Committee on Animal Use of Federal University of Health Sciences of Porto Alegre, Brazil (protocol number 220/2017).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Flávia Nathiely Silveira Fachel
    • 1
    Email author
  • Morgana Dal Prá
    • 2
  • Juliana Hofstätter Azambuja
    • 2
  • Marcelo Endres
    • 3
  • Valquíria Linck Bassani
    • 1
  • Letícia Scherer Koester
    • 1
  • Amelia Teresinha Henriques
    • 1
  • Alethea Gatto Barschak
    • 3
  • Helder Ferreira Teixeira
    • 1
  • Elizandra Braganhol
    • 2
  1. 1.Programa de Pós-Graduação em Ciências FarmacêuticasFaculdade de Farmácia, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em BiociênciasUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em PatologiaUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil

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