# Forest Volatile Organic Compounds and Their Effects on Human Health: A State-of-the-Art Review
## 4 Discussion  
### Implications for Individual Health  
Inhaling forest VOCs can result in useful antioxidant and anti-inflammatory effects on the airways, and the pharmacological activity of some terpen absorbed through inhalation may be also beneficial to promote brain function by decreasing mental fatigue, inducing relaxation, and improving cognitive performance and mood [164; 165]. The effect of these volatile compounds found in forest air is not limited to an action on the respiratory system, but, after absorption through inhalation, they are supposed to exert systemic effects, such as those on the nervous system (relaxing, anxiolytic, and antidepressant action). Evidence from laboratory studies seems to confirm these effects, thus underscoring that, in particular, limonene and pinene can modulate the release of various cytokines (for example, TNF-\(\alpha\), IL-1, IL-6), inflammatory mediators (for example, NF-kB signal transduction pathway, MAPK, COX-2 \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **Model** & **Target** & **Reference** \\ \hline \multirow{8}{*}{**Anti-inflammatory Antioxidant**} & \multirow{2}{*}{\begin{tabular}{c} Murine macrophages \\ ERK, JNK \\ \end{tabular} } & NF-kB, & [152] \\ \cline{2-3}  & & Human U373-MG cells & ROS, peroxidase & [80] \\ \cline{2-3}  & & \begin{tabular}{c} NF-kB, \\ IL-1\(\beta\), JNK, iNOS, MMP-1, \\ MMP-13 \\ \end{tabular} & [153] \\ \cline{2-3}  & & Human lymphocytes & Total antioxidant capacity & [154] \\ \cline{2-3}  & & Mouse & Ig-E, IL-4 & [149] \\ \cline{2-3}  & & \begin{tabular}{c} Wistar rats \\ IL-6 \\ CD4, CD8 and NK cells \\ \end{tabular} & \begin{tabular}{c} Superoxide dismutase, \\ [155] \\ [102] \\ \end{tabular} \\ \cline{2-3}  & & \begin{tabular}{c} Wistar rats \\ \end{tabular} & COX2 & [156] \\ \hline \multirow{8}{*}{**Anxolytic Antidepressant**} & \multirow{2}{*}{\begin{tabular}{c} Sprague–Dawley rats \\ \end{tabular} } & Sleep rhythm & [157] \\ \cline{2-3}  & & Mice & BDNF, TH, EPM test & [158] \\ \cline{2-3}  & & \begin{tabular}{c} ICR and C57 BL/6N mice \\ \end{tabular} & \begin{tabular}{c} GABA BZD receptor, \\ sleep behavior \\ Forced swim test, oxidative \\ phosphorylation expression \\ \end{tabular} & [159] \\ \cline{2-3}  & & \begin{tabular}{c} Wistar rats \\ \end{tabular} & \
\begin{tabular}{c} Sensorimotor severity score \\ \end{tabular} & [160] \\ \cline{2-3}  & & C57 BL/6 mice & Schizophrenia-like behavior & [161] \\ \hline \multirow{8}{*}{**Analgesic**} & \multirow{2}{*}{
\begin{tabular}{c} BALB/c mice \\ \end{tabular} } & Tail-flick test & [162] \\ \cline{2-3}  & & Mice & Neuropathic pain & [163] \\ \cline{2-3}  & & Wistar rats & Nociception & [156] \\ \hline \hline \end{tabular}  
* Abbreviations: BDNF, brain-derived neurotrophic factor; BZD, benzodiazep; EPM, elevated plus maze; ERK, extracellular signal-regulated kinase; GABA, \(\gamma\)-aminobutyric acid; Ig-E, immunoglobulin E; JNK, c-jun N-terminal kinase; MMP-1, metalloproteinase 1; MMP-13, metalloproteinase 13; NF-kB, nuclear factor-B; ROS, reactive oxygen species; TH, tyrosine hydroxylase.  
\end{table} 
Table 8: Preclinical evidence of \(\alpha\)-pinene biological activity. activity), and neurotransmitters (for example, dopamine levels, action on GABA receptors) in such a way as to reduce inflammation and pain and to improve anxiety, mood, and sleep quality (Table 5, Table 8, and Table 9). Although the magnitude of some of these pharmacological effects may be limited when inhaling such compounds during a short forest trip due to their relative atmospheric concentration (generally lower than that one prepared in experimental settings) and pharmacokinetics, even a mild action associated with psychophysical relaxation may be already beneficial for individual wellbeing. In fact, large studies aimed at thoroughly assessing pharmacokinetic and pharmacodynamic characteristics of forest VOCs in real-life situations are, to date, actually lacking, and it is only possible to formulate some plausible hypotheses.