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

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.

• Authors: Sergio M Borghi, Sandra S Mizokami, Thacyana T Carvalho, Fernanda S Rasquel-Oliveira, Camila R Ferraz, Victor Fattori, Thiago H Hayashida, Jean P S Peron, Doumit Camilios-Neto, Sergio R Ambrosio, Nilton S Arakawa, Rubia Casagrande, Waldiceu A Verri Jr
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 273 Pg. 113980 (Jun 12 2021) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 33652112 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Analgesics
• Diterpenes
• Lipopolysaccharides
• NF-kappa B
• kaurenoic acid
• Peroxidase

Topics

• Analgesics (chemistry, therapeutic use)
• Animals
• Asteraceae (chemistry)
• Diterpenes (chemistry, therapeutic use)
• Gene Expression Regulation (drug effects)
• Hyperalgesia (drug therapy)
• Lipid Peroxidation
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Molecular Structure
• NF-kappa B (genetics, metabolism)
• Pain (drug therapy)
• Peritonitis (chemically induced, drug therapy)
• Peroxidase (metabolism)