Tagitinin F has anti-inflammatory, anti-nociceptive and anti-matrix metalloproteinase properties: An in silico, in vitro and in vivo study.

Autor: Silva LP; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-001, Brazil; Center of Heath Sciences, University Jose do Rosario Vellano, Minas Gerais, Brazil., Santos EC; School of Medicine, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, Minas Gerais, 39100-000, Brazil., Borges BA; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-001, Brazil., Veloso MP; Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-001, Brazil., Chagas-Paula DA; Institute of Chemistry, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-001, Brazil., Gonçalves RV; Department of Animal Biology, Federal University of Viçosa, Viçosa, Minas Gerais, 36570-000, Brazil., Novaes RD; Institute of Biomedical Sciences, Department of Structural Biology, Federal University of Alfenas, Alfenas, Minas Gerais, 37130-001, Brazil. Electronic address: romulo.novaes@unifal-mg.edu.br.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2021 Feb; Vol. 164, pp. 105303. Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1016/j.phrs.2020.105303
Abstrakt: Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 μM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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