4.7 Article

Sesquiterpene lactones from Lychnophora species: Antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout

Journal

JOURNAL OF ETHNOPHARMACOLOGY
Volume 269, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2020.113738

Keywords

Sesquiterpene lactones; Gout; Arthritis; Neutrophil; Pain; Cytokine

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG) [APQ-01160-15, APQ-00820-19]
  2. Universidade Federal de Ouro Preto, Brazil (UFOP) [23109.003517/2018-85, 23109.004080/201988, 23109.004079/2019-53]
  3. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
  4. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil

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The study aimed to demonstrate the effects of sesquiterpene lactones isolated from Lychnophora trichocarpha and Lychnophora passerina on MSU crystal-induced arthritis in C57BL6 mice, as well as their inhibitory effects on neutrophil migration and pro-inflammatory cytokine release, and their evaluation on SOD and CAT activities in the cartilage of mice. Sesquiterpene lactones showed anti-inflammatory, antinociceptive, and antioxidant activities, suggesting potential anti-gout effects through inflammation, pain, and oxidative stress pathways.
Ethnopharmacological relevance: Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. Aim of the study: Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-alpha and IL-1 beta cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. Materials and methods: The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lac tones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1 beta and TNF-alpha concentrations, and SOD and CAT activities. Results: Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-alpha production. These compounds also demonstrated antinociceptive and antioxidant activities. Conclusion: Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro inflammatory cytokine TNF-alpha. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.

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