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Inflammation

, Volume 40, Issue 5, pp 1735–1741 | Cite as

Antipyretic Effects of Citral and Possible Mechanisms of Action

  • Maycon T. Emílio-Silva
  • Clarissa M. D. Mota
  • Clélia A. Hiruma-Lima
  • José Antunes-Rodrigues
  • Evelin C. Cárnio
  • Luiz G. S. Branco
ORIGINAL ARTICLE

Abstract

Citral is a mixture of the two monoterpenoid isomers (neral and geranial) widely used as a health-promoting food additive safe for human and animal (approved by the US Food and Drug Administration). In vitro studies have reported on the capability of citral to reduce inflammation. Here, we report antipyretic effects of citral in vivo using the most well-accepted model of sickness syndrome, i.e., systemic administration of lipopolysaccharide (LPS) to rats. Citral given by gavage caused no change in control euthermic rats (treated with saline) but blunted most of the assessed parameters related to the sickness syndrome [fever (hallmark of infection), plasma cytokines (IL-1β, IL-6, and TNF-α) release, and prostaglandin E2 (PGE2) synthesis (both peripherally and hypothalamic)]. Moreover, LPS caused a sharp increase in plasma corticosterone levels that was unaltered by citral. These data are consistent with the notion that citral has a corticosterone-independent potent antipyretic effect, acting on the peripheral febrigenic signaling (plasma levels of IL-1β, IL-6, TNF-α, and PGE2), eventually down-modulating hypothalamic PGE2 production.

KEY WORDS

endotoxin fever LPS IL-1β IL-6 TNF-α corticosterone systemic inflammation sickness syndrome 

Notes

Compliance with Ethical Standards

Funding Sources

This study was funded by Grant No. 2016/17681–9 São Paulo Research Foundation (FAPESP) and National Council for Scientific and Technological Development (CNPq), Brazil.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Maycon T. Emílio-Silva
    • 1
  • Clarissa M. D. Mota
    • 1
  • Clélia A. Hiruma-Lima
    • 2
  • José Antunes-Rodrigues
    • 1
  • Evelin C. Cárnio
    • 3
  • Luiz G. S. Branco
    • 4
  1. 1.Medical School of Ribeirão PretoUniversity of São PauloSão PauloBrazil
  2. 2.Natural Products Laboratory, Department of Physiology, Bioscience InstituteUniversidade Estadual Paulista ‘Júlio de Mesquita Filho’São PauloBrazil
  3. 3.Nursing School of Ribeirão PretoUniversity of São PauloSão PauloBrazil
  4. 4.Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil

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