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

Abstract

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.

• Authors: Laíla Pereira Silva, Eliziária Cardoso Santos, Bruno Arantes Borges, Marcia Paranho Veloso, Daniela Aparecida Chagas-Paula, Reggiani Vilela Gonçalves, Rômulo Dias Novaes
• Journal: Pharmacological research (Pharmacol Res) Vol. 164 Pg. 105303 (02 2021) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 33212290 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• Lipopolysaccharides
• Membrane Proteins
• Sesquiterpenes
• Tnf protein, mouse
• Tumor Necrosis Factor-alpha
• Leukotriene B4
• tagitinin
• Carrageenan
• Collagen
• Arachidonate 5-Lipoxygenase
• Ptgs2 protein, mouse
• Cyclooxygenase 1
• Cyclooxygenase 2
• Ptgs1 protein, mouse
• Matrix Metalloproteinase 13
• Mmp13 protein, mouse
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Dinoprostone

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Arachidonate 5-Lipoxygenase (metabolism)
• Carrageenan
• Cicatrix (drug therapy, metabolism)
• Collagen (metabolism)
• Cyclooxygenase 1 (metabolism)
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Edema (chemically induced, drug therapy)
• Hyperalgesia (drug therapy)
• Leukotriene B4 (metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Matrix Metalloproteinase 13 (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred BALB C
• RAW 264.7 Cells
• Sesquiterpenes (pharmacology, therapeutic use)
• Touch
• Tumor Necrosis Factor-alpha (metabolism)