Anti-inflammatory activity of neral and geranial isolated from fruits of Litsea cubeba Lour

• The first study on the anti-inflammatory cellular molecular mechanisms of the two isomers of citral, neral and geranial.
• Neral and geranial were also found to have the ability to inhibit inflammasomes.
• Neral and geranial induced different intracellular molecular responses and expression of ROS in macrophages.

Fruits of Litsea cubeba are a spicy condiment, frequently used in the aboriginal cuisine of Taiwan. Earlier studies found that the fruit contains a high amount of citral, which is also a commonly used food additive ingredient. In this study, we separated citral into neral and geranial in pure forms. At 66 µM dose, neral showed greater inhibition of TNF-α and IL-6 secretion of macrophages after stimulation by LPS than did geranial; with 81.4 and 58.2% vs. 63.6 and 46.8%, respectively. Furthermore, compared with geranial, neral demonstrated better efficacy in inhibiting expression of the inflammatory mediators pro-IL-1β, iNOS, COX-2 and NLRP-3. Both neral and geranial exhibited significant and similar inhibition of NLRP-3 inflammasome-mediated IL-1β secretion; however, the two compounds had different inhibitory effects on the phosphorylation of ERK1/2, JNK1/3, p38 and IκB. This is the first study reporting the differences between the anti-inflammatory cellular molecular mechanisms of the two isomers of citral, neral and geranial, which may be regarded as components of functional food ingredients.