The ethanolic extract of Terminalia argentea Mart. & Zucc. bark reduces the inflammation through the modulation of cytokines and nitric oxide mediated by the downregulation of NF-kappa B

Author(s)

de Araujo Moreira, Mirella dos Reis ^[1] ; Sales-Campos, Helioswilton ^{[2, 3]} ; Fontanari, Caroline ^[1] ; Galvao Meireles, Alyne Favero ^[1] ; Borges Prado, Morgana Kelly ^[1] ; Zoccal, Karina Furlani ^{[4, 1]} ; Sorgi, Carlos Arterio ^[1] ; da Silva, Cristiane Tefe ^[4] ; Groppo, Milton ^[5] ; Faccioli, Lucia Helena ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[3] Univ Fed Goias, Inst Patol Trop & Saude Publ, Goiania, Go - Brazil

^[4] Ctr Univ Barao Maua, Ribeirao Preto, SP - Brazil

^[5] Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Ethnopharmacology; v. 261, OCT 28 2020.
• Web of Science Citations: 0

Abstract

Ethnopharmacological relevance: Terminalia argentea Mart. \& Zucc. (Combretaceae), popularly known as ``capitao do campo{''}, is native from the Brazilian cerrado, which is used in folk medicine to treat inflammatory diseases. Aim of the study: We aimed to investigate the anti-inflammatory effects, toxicity and mechanisms of action regarding the use of the hydmalcoholic extract of T. argentea bark. Materials and methods: Toxicity was determinate in vitro using the macrophage lineage J774.1 without LPS. Cells were treated with 0.5; 2; 8; 32 and 125 mu g/mL of the plant extract. Cell viability was assessed by MTT colorimetric assay. The production of nitrite and cytokines was also determined in the supernatants. A NF-kappa B reporter assay using RAW macrophages was employed to elucidate the impact of the plant extract on the expression of such molecule. In mice, toxicity was assessed by orally given an intermediate to high concentration of the plant extract on a single dose (1000 or 5000 mg/kg) or low and intermediate doses (300 or 1000 mg/kg) twice daily for 14 days. Blood samples were collected for biochemical analysis. The anti-inflammatory activity was assessed using the air-pouch model with or without pre-inoculation with the inflammatory stimuli LPS (0.5 mu g/mL), followed by treatment with plant extract at 5, 60 or 300 mg/kg administered in the air pouch (subcutaneous injection). After 4 h, mice were euthanized and the air pouches washed with 2 mL heparinized PBS (10 IU/mL). Then, the local production in the air pouch wash of cytokines, total proteins and leukocytes was assessed. Results: No signals of toxicity were observed either in cells or mice. Regardless the concentration used in vitro, the extract exhibited a significant anti-inflammatory activity, as perceived by the reduction of the inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 and nitrites on cell supernatants. This was concomitant with a downregulation in NF-kappa B and elevated levels of IL-10. In mice, similar effects were observed, especially when the plant extract was given at 300 mg/kg, inhibiting the release of IL-1 beta, TNF-alpha, IL-6 and proteins, as well as increasing the release of IL-10. Conclusions: Altogether, our results demonstrated that the hydroalcoholic extract of T. argentea bark has anti-inflammatory activity without inducing toxicity in cells or living animals. This activity seems to be chiefly influenced by a downregulation in NF-kappa B, inflammatory cytokines and production of nitrite along with augmented concentration of IL-10. (AU)

• FAPESP's process: 14/03332-7 - Study of the relationship between inflammasome activation and lipid mediators production with pulmonary inflammation induced by scorpion venom with and without hyaluronidase
• Grantee: Karina Furlani Zoccal
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants