Abstract
Six flavonoids were identified and isolated from the ethanolic extract of Alternanthera tenella Colla (Amaranthaceae) whole plant (EEAT) including 2″-O-β-d-glucopyranosyl-vitexin (A19). Flavonoids have anti-inflammatory activity; however, the 2″-O-β-d-glucopyranosyl-vitexin anti-inflammatory property was not totally explored. The aim of the present study was to investigate the anti-inflammatory effects of ethanolic extract from A. tenella whole plant and isolated flavone C-glycoside A19 in models of inflammation. The oral administration (p.o.) of EEAT (30, 100, and 300 mg/kg), A19 (0.1, 1, and 10 mg/kg), and prednisolone (3 mg/kg) were tested against the carrageenan-induced paw edema in Swiss mice. The EEAT (100 mg/kg, p.o.), A19 (1 mg/kg, p.o.), and prednisolone (3 mg/kg, p.o.) were tested in the zymosan-articular inflammation, carrageenan-pleurisy, and complete Freund’s adjuvant (CFA) models in Swiss mice. In silico analysis and search for structural relationships between vitexin derivatives flavones present in the EEAT and TNF-α inhibitors were performed. EEAT, A19, and prednisolone significantly inhibited (i) edema, mechanical hyperalgesia in carrageenan-induced paw inflammation; (ii) leukocyte migration and protein extravasation in carrageenan-induced pleurisy; (iii) knee edema, mechanical hyperalgesia, and leukocyte migration in articular inflammation induced by zymosan. Still the CFA induced the increase in myeloperoxidase and N-acetylglucosaminidase activities, EEAT, A19, and prednisolone significantly inhibited these enzymes. The in silico analysis showed that molecules with similar structure to apigenin and vitexin have a potential inhibition on the TNF system. This study confirms the anti-inflammatory properties of EEAT and A19. The C-glycosylated flavone A19 could be responsible for the EEAT anti-edematogenic and anti-hyperalgesic effects and a potential TNF-α inhibitor.
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Acknowledgements
The authors are grateful to CNPq for scholarships and financial support, FUNDECT (Fundação de Amparo à Pesquisa, Desenvolvimento Científico e Tecnológico do Mato Grosso do Sul), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, financial code 001), FAPESP, and FAEPEX-UNICAMP (Fundo de Apoio ao Ensino, à Pesquisa e à Extensão). We are also grateful to Prof. Dr. Josafá Carlos de Siqueira for identification of the plant.
Funding
This study was funded by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico ((CNPq): #311166/2016-4; #427859/2018-2; #304266/2017-5) and by Fundação de Amparo à Pesquisa do Estado de São Paulo ((FAPESP): 2017/09781-6; 2015/03726-8 and 2006/06079-4)).
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RMK, ES, AGJ, and CALK performed the in vivo inflammation assays. FHB, TFP, JVNV, and MJS prepared the EEAT and isolated A19. FHB and MJS performed in silico analysis. MJS, AGJ, RMK, and CALK ensured statistical analysis, and wrote and corrected the manuscript.
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Kassuya, R.M., dos Santos, E., Bosso, F.H. et al. Anti-inflammatory Properties of Ethanolic Extract and 2″-O-β-d-Glucopyranosyl-vitexin Obtained from Alternanthera tenella Colla Whole Plant. Inflammation 44, 1540–1552 (2021). https://doi.org/10.1007/s10753-021-01438-7
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DOI: https://doi.org/10.1007/s10753-021-01438-7