2. Academic Validation
  3. The diterpene from Sphagneticola trilobata (L.) Pruski, kaurenoic acid, reduces lipopolysaccharide-induced peritonitis and pain in mice

The diterpene from Sphagneticola trilobata (L.) Pruski, kaurenoic acid, reduces lipopolysaccharide-induced peritonitis and pain in mice

  • J Ethnopharmacol. 2021 Jun 12:273:113980. doi: 10.1016/j.jep.2021.113980.
Sergio M Borghi 1,  Sandra S Mizokami 2,  Thacyana T Carvalho 3,  Fernanda S Rasquel-Oliveira 4,  Camila R Ferraz 5,  Victor Fattori 6,  Thiago H Hayashida 7,  Jean P S Peron 8,  Doumit Camilios-Neto 9,  Sergio R Ambrosio 10,  Nilton S Arakawa 11,  Rubia Casagrande 12,  Waldiceu A Verri Jr 13
Affiliations

Affiliations

  • 1 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil; Centro de Pesquisa Em Ciências da Saúde, Universidade Norte Do Paraná, 86041-140, Londrina, Paraná, Brazil. Electronic address: sergio_borghi@yahoo.com.br.
  • 2 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: sandramizokami@hotmail.com.
  • 3 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: thacy_thacy@yahoo.com.br.
  • 4 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: fernandarasquel@gmail.com.
  • 5 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: camila_ferraz96@hotmail.com.
  • 6 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: vfattori@outlook.com.
  • 7 Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350, Londrina, Paraná, Brazil. Electronic address: thiago_hhayashida@hotmail.com.
  • 8 Department of Immunology, Institute of Biomedical Sciences, Ed. Biomédicas IV, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 1730, 05508-900, São Paulo, Brazil. Electronic address: jeanpierre@usp.br.
  • 9 Department of Biochemistry and Biotechnology, Exact Sciences Center, Londrina State University, Londrina, 86057-970, Brazil. Electronic address: camiliosneto@uel.br.
  • 10 Núcleo de Pesquisa Em Ciências Exatas e Tecnológicas, Universidade de Franca, 14404-600, Franca, São Paulo, Brazil. Electronic address: sergio.ambrosio@unifran.edu.br.
  • 11 Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350, Londrina, Paraná, Brazil. Electronic address: arakawans@uel.br.
  • 12 Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350, Londrina, Paraná, Brazil. Electronic address: rubiacasa@uel.br.
  • 13 Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: waldiceujr@yahoo.com.br.
PMID: 33652112 DOI: 10.1016/j.jep.2021.113980
Abstract

Ethnopharmacological relevance: Sphagneticola trilobata (L.) Pruski is a plant species belonging to the Asteraceae family. Kaurenoid acid (KA) is a diterpene metabolite and one of the active ingredients of Sphagneticola trilobata (L.) Pruski. Extracts containing KA are used in traditional medicine to treat pain, inflammation, and Infection.

Aim: The goal of the present study was to investigate the in vivo effects of KA (1-10 mg/kg, per oral gavage) upon LPS inoculation in mice by intraperitoneal (i.p.) or intraplantar (i.pl.; subcutaneous plantar injection) routes at the dose of 200 ng (200 μL or 25 μL, respectively).

Methods: In LPS paw inflammation, mechanical and thermal hyperalgesia MPO activity and oxidative imbalance (TBARS, GSH, ABTS and FRAP assays) were evaluated. In LPS peritonitis we evaluated leukocyte migration, cytokine production, oxidative stress, and NF-κB activation.

Results: KA inhibited LPS-induced mechanical and thermal hyperalgesia, MPO activity and modulated redox status in the mice paw. Pre- and post-treatment with KA inhibited migration of neutrophils and monocytes in LPS peritonitis. KA inhibited the pro-inflammatory/hyperalgesic cytokine (e.g., TNF-α, IL-1β and IL-33) production while enhanced anti-inflammatory/analgesic cytokine IL-10 in peritoneal cavity. In agreement with the effect of KA over pro-inflammatory cytokines it inhibited oxidative stress (total ROS, superoxide production and superoxide positive cells) and NF-κB activation during peritonitis.

Conclusion: KA efficiently dampens LPS-induced peritonitis and hyperalgesia in vivo, suggesting it as a suitable candidate to control excessive inflammation and pain during gram-negative Bacterial infections and bringing mechanistic explanation to the ethnopharmacological application of Sphagneticola trilobata (L.) Pruski in inflammation and Infection.

Keywords

Cytokines; Kaurenoic acid; LPS-Induced inflammation and pain; Leukocytes; Oxidative stress.

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