Costic acid, a sesquiterpene from Nectandra barbellata (Lauraceae), attenuates sponge implant-induced inflammation, angiogenesis and collagen deposition in vivo

Author(s)

Ferreira, Bruno Antonio ; Moura, Francyelle Borges Rosa de ; Cassimiro, Isabella Silva ; Londero, Vinicius Silva ; Gonsalves, Marina de Monroe ; Lago, Joao Henrique Ghilardi ; Araujo, Fernanda de Assis

• Document type: Journal article
• Source: Fitoterapia; v. 175, p. 9-pg., 2024-04-04.

Abstract

Sesquiterpenes are a class of metabolites derived from plant species with immunomodulatory activity. In this study, we evaluated the effects of treatment with costic acid on inflammation, angiogenesis, and fibrosis induced by subcutaneous sponge implants in mice. One sponge disc per animal was aseptically implanted in the dorsal region of the mice and treated daily with costic acid (at concentrations of 0.1, 1, and 10 mu g diluted in 10 mu L of 0.5% DMSO) or 0.5% DMSO (control group). After 9 days of treatment, the animals were euthanized, and the implants collected for further analysis. Treatment with costic acid resulted in the reduction of the inflammatory parameters evaluated compared to the control group, with a decrease in the levels of inflammatory cytokines and chemokines (TNF, CXCL-1, and CCL2) and in the activity of MPO and NAG enzymes. Costic acid administration altered the process of mast cell degranulation. We also observed a reduction in angiogenic parameters, such as a decrease in the number of blood vessels, the hemoglobin content, and the levels of VEGF and FGF cytokines. Finally, when assessing implant-induced fibrogenesis, we observed a reduction in the levels of the pro-fibrogenic cytokine TGF-beta 1, and lower collagen deposition. The results of this study demonstrate, for the first time, the antiinflammatory, anti-angiogenic, and anti-fibrotic effects of costic acid in an in vivo model of chronic inflammation and reinforce the therapeutic potential of costic acid. (AU)

• FAPESP's process: 23/12447-1 - Searching for specialized metabolites from Brazilian floristic biodiversity as drug candidates for neglected tropical diseases
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants