Table 7.

Anti-inflammatory activity of citral, its isomers, and citral-rich EOs.

Citral/EO Citral Rich/Constituent	Concentration	Animal/Cell Line Tested	Results	Ref.
Citral	5–100 μg/well	Peritoneal macrophage of male BALB/c mice	50 and 100 μg of citral significantly inhibited IL-1β and IL-10 release and LPS activation. IL-6 production by macrophages significantly decreased at citral concentrations of 5, 10, 25, 50, and 100 μg/well).	[99]
Citral	0.36, 0.15, and 0.06 g/kg	MRSA-infected mice	Citral significantly reduced the levels of TNF-α, IL-6, IL-1β, malondialdehyde, and hydroxyl radicals. Increased superoxide dismutase and glutathione enzyme levels. Reduced the lung inflammatory infiltrates infected by MRSA.	[100]
Citral	300 mg/kg	Diabetes-induced rats	Gene expression of IL-6 and TNF-α in the liver were significantly downregulated.	[101]
Citral	50–300 mg/kg	Paw edema-induced mice	Reversed paw edema formation in mice induced by LPS and zymosan, inducers of TLR4 and TLR2 signaling.	[42]
Citral	300 mg/kg	Eutrophic and obese mice	Citral reduced TNF-α and serum leptin concentration after the LPS challenge. IL6 levels in the hypothalamus of obese mice were reduced.	[102]
Citral	125, 250, and 500 mg/kg	Male Swiss mice	Citral reduced NO production and inhibited neutrophil migration in liver.	[103]
Citral	10, 20, and 40 mg/kg 3, 6, and 12 µg/mL	Mice with LPS-induced acute lung injury Alveolar macrophages	On in vivo LPS-induced acute lung injury, citral reduced TNF-α, IL-6, and IL-1β production. In vitro, citral inhibited the production of TNF-α, IL-6, and IL-1β in alveolar macrophages. The mechanism was associated with PPAR-γ activation.	[104]
Citral, neral, and geranial	66 µM	Murine J774A.1 macrophages	Citral inhibited TNF-α and IL-6. Pure neral inhibited TNF-α secretion by 60–80%, whereas geranial 57–75%. Both neral and geranial reduced IL-6 secretion of LPS-stimulated macrophages and the expression of inflammatory mediators IL-1β, iNOS, COX-2, and NLRP-3.	[105]
Citral-rich fractions of Citrus lemon EO	0.005, 0.01, and 0.02%	Murine macrophage RAW264.7 cell line	Reduced the expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced macrophages.	[106]
Cymbopogon citratus EO	0.1%	Pre-inflamed human dermal fibroblasts	Significantly inhibited the production of the inflammatory biomarkers: vascular cell adhesion molecule 1 (VCAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG).	[107]
Myrcia ovata EO	200 and 300 mg/kg	Male Swiss mice with induced acute inflammation	Reduced leukocyte extravasation and inhibited TNF-α production by 50% and 69% at both concentrations, as well as IL-1β production by 47%.	[108]