Agathisflavone as a Single Therapy or in Association With Mesenchymal Stem Cells Improves Tissue Repair in a Spinal Cord Injury Model in Rats.

Autor:	do Nascimento RP; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., de Jesus LB; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Oliveira-Junior MS; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Almeida AM; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Moreira ELT; Department of Anatomy, Pathology and Veterinary Clinics, Hospital of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil., Paredes BD; Center for Biotechnology and Cell Therapy, São Rafael Hospital, D'Or Institute for Research and Education, Salvador, Brazil., David JM; Department of General and Inorganic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador, Brazil., Souza BSF; Center for Biotechnology and Cell Therapy, São Rafael Hospital, D'Or Institute for Research and Education, Salvador, Brazil.; Gonçalo Moniz Institute, FIOCRUZ-BA, Salvador, Brazil., de Fátima D Costa M; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; INCT-Translational Neuroscience (INCT-TN, BR), Salvador, Brazil., Butt AM; School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom., Silva VDA; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; INCT for Excitotoxicity and Neuroprotection (INCT-EN, BR), Salvador, Brazil., Costa SL; Laboratory of Neurochemistry of Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Gonçalo Moniz Institute, FIOCRUZ-BA, Salvador, Brazil.; INCT for Excitotoxicity and Neuroprotection (INCT-EN, BR), Salvador, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2022 Apr 05; Vol. 13, pp. 858190. Date of Electronic Publication: 2022 Apr 05 (Print Publication: 2022).
DOI:	10.3389/fphar.2022.858190
Abstrakt:	Agathisflavone is a flavonoid with anti-neuroinflammatory and myelinogenic properties, being also capable to induce neurogenesis. This study evaluated the therapeutic effects of agathisflavone-both as a pharmacological therapy administered in vivo and as an in vitro pre-treatment aiming to enhance rat mesenchymal stem cells (r)MSCs properties-in a rat model of acute spinal cord injury (SCI). Adult male Wistar rats ( n = 6/group) underwent acute SCI with an F-2 Fogarty catheter and after 4 h were treated daily with agathisflavone (10 mg/kg ip, for 7 days), or administered with a single i.v. dose of 1 × 10 6 rMSCs either unstimulated cells (control) or pretreated with agathisflavone (1 µM, every 2 days, for 21 days in vitro ). Control rats ( n = 6/group) were treated with a single dose methylprednisolone (MP, 60 mg/kg ip). BBB scale was used to evaluate the motor functions of the animals; after 7 days of treatment, the SCI area was analyzed after H&E staining, and RT-qPCR was performed to analyze the expression of neurotrophins and arginase. Treatment with agathisflavone alone or with of 21-day agathisflavone-treated rMSCs was able to protect the injured spinal cord tissue, being associated with increased expression of NGF, GDNF and arginase, and reduced macrophage infiltrate. In addition, treatment of animals with agathisflavone alone was able to protect injured spinal cord tissue and to increase expression of neurotrophins, modulating the inflammatory response. These results support a pro-regenerative effect of agathisflavone that holds developmental potential for clinical applications in the future. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 do Nascimento, de Jesus, Oliveira-Junior, Almeida, Moreira, Paredes, David, Souza, de Fátima D. Costa, Butt, Silva and Costa.)
Databáze:	MEDLINE
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