## 3 Biological Activities
### Anti-Inflammatory
In another study, the potential of citral to reduce LPS-induced inflammation was evaluated in a rat model of peritonitis and human umbilical vein endothelial cells (HUVECs). Citral (40 mg/kg) was injected intraperitoneally in rats, whereas the cell line was incubated with 3, 6, and 12 uM of citral for 12 h. Citral treatment reduced the counts of white blood cells and inflammatory cytokines IL-6 and TNF-\(\alpha\) in rats. Furthermore, TNF-\(\alpha\) and IL-8 expression and NF-\(\kappa\)B activation induced by LPS were significantly reduced by citral in HUVECs. Results conclude that the anti-inflammatory activity of citral was attributed to the activation of the PPAR-\(\gamma\) receptor, which attenuates NF-\(\kappa\)B activation and inflammatory mediator production [109]. Several other studies demonstrated the anti-inflammatory potential of citral, as shown in Figure 4[10, 110, 111, 104]. It is well known that citral, like other EOs, shows high volatility, low solubility, and bioavailability that limits its use. Therefore, several studies evaluated the effect of the encapsulation process on their anti-inflammatory potential. [PERSON], Lima [111] encapsulated citral on \(\beta\)-cyclodextrintrin (\(\beta\)-CD) and hydroxypropyl-\(\beta\)-cyclodextrintrin (HP-\(\beta\)-CD) and evaluated their potential to reduce the inflammatory process in mice. For the assay, carrageenan was administrated into the pleural space of mice to induce inflammation, increase leukocyte count, and upregulate the TNF-\(\alpha\) production in pleural fluid. It was \begin{table}
\begin{tabular}{c c c c c} \hline
**Citral/EO Citral** & **Concentration** & **Animal/Cell Line Tested** & **Results** & **Ref.** \\
**Rich/Constituent** & & & & 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 monkoline induced by gamma interferon (MIG). & [107] \\ \multirow{4}{*}{_Myrcia oenta_ EO} & \multirow{2}{*}{200 and 300 mg/kg} & Male Swiss mice with induced acute inflammation & Reduced leukocyte extravasation and inhibited TNF-\(\alpha\) production by 50\% and 69\% at both concentrations, as well as IL-1\(\beta\) production by 47\%. & [108] \\  & & & & \\ \hline \end{tabular}
\end{table} 
Table 7: _Cont._  
Figure 4: The anti-inflammatory mechanism of citral is attributed to the inhibition of NF-\(\kappa\beta\) signaling. Citral activates peroxisome proliferatorator-activated receptor (PPAR-\(\gamma\)) and inhibits lkB phosphorylation, which independently blocks NF-\(\kappa\beta\) activity with the consequent inhibition of gene expression of the inflammatory mediator [109, 110, 111, 112, 113]. observed that mice treated with non-encapsulated and encapsulated citral into \(\beta\)-CD and HP-\(\beta\)-CD (0.1 mg/g) significantly reduced total leukocyte counts and TNF-\(\alpha\) levels. Citral showed a potent anti-inflammatory activity, evaluated in many animal and cell models, highlighting those diseases induced by PAMPs, such as LPS of bacteria. Figure 4 resumes some reported mechanisms by which citral exerted anti-inflammatory activity. In general, these include the blockage of NF-\(\kappa\beta\) signaling, which activates gene expression of inflammatory mediators [109; 112].