Antipyretic Effects of Citral and Possible Mechanisms of Action

Emílio-Silva MT, Mota CMD, Hiruma-Lima CA, Antunes-Rodrigues J, Cárnio EC, Branco LGS
Inflammation, 2017


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.


Emílio-Silva MT, Mota CMD, Hiruma-Lima CA et al. Antipyretic Effects of Citral and Possible Mechanisms of Action. Inflammation. 2017 Jun 30. doi: 10.1007/s10753-017-0615-4.

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