Abstract
This study aims to investigate the activity of n-hexane, ethyl acetate and butanol fractions obtained from Arrabidaea chica Verlot against MIA-induced osteoarthritis (OA). The antinociceptive potentials of each fraction were evaluated through a cyclooxygenase (COX) 1 and 2 inhibition test and an in vivo OA-model. In addition, toxicity assessments in the liver, spleen and kidney, as well as radiographic and histopathological knee analyses, were performed. The chemical composition of the n-hexane fraction was elucidated, and a molecular docking protocol was carried out to identify which compounds are associated with the detected bioactivity. The n-hexane A. chica fraction preferentially inhibits COX-2, with 90% inhibition observed at 10 µg/mL. The fractions also produced significant improvements in OA incapacity, motor activity and hyperalgesia parameters and in radiological knee conditions. However, concerning the histopathological evaluations, these improvements were only significant in the hexane and ethyl acetate fraction treatments, which resulted in better average scores, suggesting that these fractions slow OA-promoted joint injury progression. Histopathological organ analyses indicate that the fractions are not toxic to animals. Twenty compounds were identified in the n-hexane fraction, comprising fatty acids, terpenes and phytosterols. In silico analyses indicate the presence of favourable interactions between some of the identified compounds and the COX–2 enzyme, mainly concerning alpha-tocopherol (Vitamin E), squalene and beta-sitosterol. The findings indicate that A. chica fractions display analgesic, anti-inflammatory properties, are non-toxic and are able to slow OA progression, and may, therefore, be prioritized as natural products in OA human clinical trials.
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Abbreviations
- OA:
-
Osteoarthritis
- IL-1:
-
Interleukin-1
- IL-6:
-
Interleukin-6
- COX-1:
-
Cyclooxygenase-1
- COX-2:
-
Cyclooxygenase-2
- NSAIDS:
-
Nonsteroidal anti-inflammatory drugs
- Hex:
-
N-Hexane
- EtAc:
-
Ethyl acetate
- But:
-
Butanol
- SISGEN:
-
National System of Genetic Heritage Management and Associated Traditional Knowledge
- ECAU:
-
Ethics Committee in Animal Use
- UFMA:
-
Federal University of Maranhão
- MIA:
-
Sodium monoiodoacetate
- NaCl:
-
Sodium chloride (saline)
- APW:
-
Affected paw weight
- CPW:
-
Contralateral paw weight
- EDTA:
-
Ethylenediaminetetraacetic acid
- OARSI:
-
Osteoarthritis Research Society International
- GC/MS:
-
Gas chromatograph and mass spectrometry
- EI-MS:
-
Electron-impact mass spectra
- DFT:
-
Density functional theory
- ANOVA:
-
Analysis of variance
- iNOS:
-
Inducible nitric oxide synthase
- PGE2:
-
Prostaglandin E2
- TNF-α:
-
Tumour necrosis factor-α
- NF-κB:
-
Nuclear factor kappa B
- p38MAPK:
-
P38 mitogen-activated protein kinases
- DPPH:
-
2,2-Diphenyl 1 picrylhydrazyl
- ABTS:
-
2,2′-Azinobis-3-ethylbenzothiazoline-6-sulfonic acid
- NO:
-
Nitric oxide
- IL-1β:
-
Interleukin-1β
- IFN-γ:
-
Interferon-gamma
- LPS:
-
Lipopolysaccharide
- PBMC:
-
Peripheral blood mononuclear cell
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Acknowledgements
The authors like to thank the Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) for financial support (Universal 871/17 grant process) and for the PhD scholarship given to Cleydlenne Vasconcelos and the Federal University of Ceará (UFC) National High-Performance Processing Center (Centro Nacional de Processamento de Alto Desempenho/CENAPAD-UFC) for providing the computational resources used in this study.
Funding
This research was funded by the Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) Process Universal 871/17.
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Vasconcelos, C.C., Lopes, A.J.O., de Jesus Garcia Ataide, E. et al. Arrabidaea chica Verlot fractions reduce MIA-induced osteoarthritis progression in rat knees. Inflammopharmacol 29, 735–752 (2021). https://doi.org/10.1007/s10787-021-00803-0
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DOI: https://doi.org/10.1007/s10787-021-00803-0