## 3 Biological Activities
### Anti-Inflammatory  
The anti-inflammatory potential showed by citral has been previously reported (Table 7). [PERSON], [PERSON] [10] evaluated the anti-inflammatory activity of citral in male mice infected with _S. aureus. This bacterium_ is one of the most pathogenic species of the staphylococci group and causes several diseases, such as skin diseases, bacteremia, septic arthritis, and respiratory infections. _S. aureus_ triggers inflammation and recruitment of neutrophils, critical responses for pathogen clearance but associated with substantial tissue damage. Results indicated that citral inhibited the expression of NO synthase and some features of acute inflammation, such as monocyte numbers and the gene transcription of the pro-inflammatory cytokine TNF-\(\alpha\). The anti-inflammatory activity of citral in RAW 264.7 cells (mouse macrophages, Abelson murine leukemia virus-induced tumor) in the presence and absence of lipopolysaccharide-ascacharide (LPS) was evaluated by [PERSON], [PERSON] [98]. Citral inhibited NO production in 84 and 99% at the lowest (5 ug/mL) and highest tested concentrations (20 ug/mL). \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Citral/EO Citral** & **Concentration** & **Animal/Cell Line Tested** & **Results** & **Ref.** \\ \hline \hline \multirow{4}{*}{Citral} & \multirow{4}{*}{5–100 ug/well} & \multirow{4}{*}{Peritoneal macrophage male BALB/c mice} & 50 and 100 ug of citral significantly inhibited IL-1\(\upbeta\) and IL-10 release and LPS activation. & \multirow{4}{*}{[99]} \\  & & & & IL-6 production by macrophages significantly \\  & & & & decreased at citral concentrations of 5, 10, 25, 50, \\  & & & & and 100 ug/well). & \\ \multirow{4}{*}{Citral} & \multirow{4}{*}{0.36, 0.15, and 0.06 g/kg} & \multirow{4}{*}{MRSA-infected mice} & \multirow{4}{*}{Increased superoxide dismutase and glutathione enzyme levels.} & \multirow{4}{*}{[100]} \\  & & & & IL-6 production by macrophages significantly \\  & & & & and 100 ug/well). & \\ \multirow{4}{*}{Citral} & \multirow{4}{*}{300 mg/kg} & \multirow{4}{*}{Diabetes-induced rats} & \multirow{4}{*}{Gene expression of IL-6 and TNF-\(\alpha\) in the liver were significantly downregulated.} & \multirow{4}{*}{[101]} \\  & & & & Reversed paw edema formation in mice induced by LPS and zymosan, inducers of TLR4 and TLR2 signaling. & \multirow{4}{*}{[42]} \\  & & & & Citral reduced TNF-\(\alpha\) and serum leptin concentration after the LPS challenge. & \multirow{4}{*}{[102]} \\  & & & & IL6 levels in the hypothalamus of obese mice were reduced. & \\ \multirow{4}{*}{Citral} & \multirow{4}{*}{125, 250, and 500 mg/kg} & \multirow{4}{*}{Male Swiss mice} & \multirow{4}{*}{Citral reduced NO production and inhibited neutrophil migration in liver.} & \multirow{4}{*}{[103]} \\  & & & & On in vivo LPS-induced acute lung injury, citral reduced TNF-\(\alpha\), IL-6, and IL-1\(\upbeta\) production. & \\ \multirow{4}{*}{Citral} & \multirow{4}{*}{3, 6, and 12 ug/mL} & \multirow{4}{*}{Mice with LPS-induced acute lung injury} & \multirow{4}{*}{In vitro, citral inhibited the production of TNF-\(\alpha\), IL-6, and IL-1\(\upbeta\) in alveolar macrophages. The mechanism was associated with PPAR-\(\upgamma\) activation.} & \multirow{4}{*}{Citral inhibited TNF-\(\alpha\) and IL-6.} \\  & & & & Pure neral inhibited TNF-\(\alpha\) secretion by 60-80\%, whereas germinal 57–75\%. & \\ \multirow{4}{*}{Citral, neral, and geraial} & \multirow{4}{*}{66 \(\upmu\)M} & \multirow{4}{*}{Murine J774A.1 macrophages} & \multirow{4}{*}{Both metal and geraial reduced IL-6 secretion of LPS-stimulated macrophages and the expression of inflammatory mediators IL-1\(\upbeta\), iNOS, COX-2, and NLRP-3.} & \multirow{4}{*}{[105]} \\  & & & & Reduced the expression of the pro-inflammatory cytokines TNF-\(\upalpha\), IL-1\(\upbeta\), and IL-6 in LPS-induced macrophages. & \\ \hline \hline \end{tabular}
\end{table} 
Table 7: Anti-inflammatory activity of citral, its isomers, and citral-rich EOs.