In vitro effects of citral on the human myometrium: Potential adjunct therapy to prevent preterm births

Background: Premature infants contribute to infant morbidity and mortality especially in low resource settings. Information on tocolytic and/or anti-inflammatory effects of several plant extracts, such as citral, could help prevent preterm birth cases and reduce the number of preterm infants. The aim of this study was to evaluate the in vitro tocolytic and anti-inflammatory effect of citral on myometrial tissues of the human uterus. Methods: Myometrial samples from uteri obtained after hysterectomy were used in functional tests to evaluate the inhibitory effect of citral on PGF-2α induced contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to citral in human myometrial homogenates were measured by ELISAs. Forskolin was used as a positive control. The anti-inflammatory effect of citral was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, and the anti-inflammatory cytokine IL-10, in human myometrial explants stimulated with lipopolysaccharide (LPS). Results: Citral was able to induce a significant inhibition of PGF-2α induced contractions at the highest concentration level (p <.05). Citral caused a concentration-dependent increase in myometrial cAMP levels (p <.05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1β production, while IL-10 production increased significantly (p <.05). The anti-inflammatory and tocolytic effects induced by citral could be associated with an increase in cAMP levels in human myometrial samples. Conclusion: These properties place citral as a potentially safe and effective adjuvant agent in preterm birth cases, an obstetric and gynecological problem that requires urgent attention.