# Forest Volatile Organic Compounds and Their Effects on Human Health: A State-of-the-Art Review
## 4 Discussion
### Implications for Individual Health
\begin{table}
\begin{tabular}{c c c} \hline \hline
**Molecule** & **Effects** & **Mechanisms** & **References** \\ \hline \multirow{8}{*}{**D-Limonene**} & \multirow{8}{*}{Anti-inflammatory} & It inhibits the synthesis or release of \\  & & pro-inflammatory mediators (TNF-\(\alpha\), NO, \\  & & IL-1, IL-6, IL-5, IL-13, TGF-\(\beta\)), enzymes \\  & & (5-LOX, COX-2, NOG), transcription factors \\  & & (NF-\(\kappa\)B), and mitogen-activated protein (MAP) \\  & & kinase family members (p38, JNK, ERK). \\ \hline \multirow{8}{*}{**D-Limonene**} & \multirow{8}{*}{Antioxidant} & It inhibits caspase-3/caspase-9 activation, \\  & & increases the activities of cell antioxidant enzymes (catalase, peroxidase) and the \\ \cline{1-1}  & & Bcl-2/Bax ratio. \\ \cline{1-1} \cline{2-4}  & & It induces phase II carcinogen-metabolizing \\ \cline{1-1}  & & enzymes, inhibits phenyl-transferase activity, \\ \cline{1-1}  & & increases cell autophagy (via MAP11C3B, \\ \cline{1-1}  & & mitochondrial death pathway, the PI3K/Akt \\ \cline{1-1}  & & pathway, and caspase-3 and 9 activity) and \\ \cline{1-1}  & & differentiation, reduces cyclin-DI and increases \\ \cline{1-1}  & & TGF-\(\beta\) signaling, decreases tumor-induced \\ \cline{1-1}  & & immunosuppressivepression, reduces circulating \\ \cline{1-1}  & & Vascular Endothelial Growth Factor (VEGF) \\ \cline{1-1}  & & and blocks the receptor VEGF-RI, increases \\ \cline{1-1}  & & DNA damage repair and PARP cleavage. \\ \cline{1-1}  & & It modulates the expression of the chemotactic \\ \cline{1-1}  & & protein MCP-1 and of the proteolytic enzymes \\ \cline{1-1}  & & MMP-2, MMP-9. \\ \hline \hline \end{tabular}
\end{table} 
Table 9: Summary of preclinical evidence relative to biological activities of the five most common forest VOCs [3, 30, 34, 35, 36, 37]. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Molecule** & **Effects** & **Mechanisms** & **References** \\ \hline \multirow{8}{*}{Antinociceptive} & Bimodal activity: topically applied, it seems capable of eliciting pain, via interaction with TRPA1 ion channels, while in other modes of administration, it has shown antinociceptive effects in different experimental models. & [24, 90, 116, 137] \\ \cline{2-3}  & & It shows some degree of efficacy in mice and rat models. & [90, 127, 135] \\ \cline{2-3}  & Antidepressant & It shows some degree of efficacy in mice and rat models. & [132, 133, 134] \\ \hline \multirow{8}{*}{**a-Pinene**} & Anxiolytic, sedative & In several animal models, it enhances sleep by eating as a positive modulator for GABAA-A-BZD receptors, prolonging GABAergic inhibitory signaling. & [155, 157, 158, 159, 160, 161] \\ \cline{2-3}  & Antiinflammatory & It modulates NF-\(\pi\)B and IsRa, ERK, JNK, IL-1B, IL-6, INOS (and NO secretions), MMP-1, MMP-1, MMP-1, ISOX-2. & [146, 152, 153, 155, 156] \\ \cline{2-3}  & Antioxidant & It reduces ROS production, caspase-3 activity, modulates superoxide dismutase, catalase, peroxidase activity, NO and IL-6 secretions. & [146, 155, 168] \\ \cline{2-3}  & Antiproliferative & It acts on efflux pumps responsible for multidrug-resistant tumors and on cell cycle arrest via the cyclin-B protein. & [147, 148] \\ \cline{2-3}  & Analgesic & It shows some degree of efficacy in animal models. & [156, 162, 163] \\ \hline \multirow{8}{*}{\(\beta\)-Pinene} & Anxiolytic, antidepressant & It binds to the GABA-A receptor, prolonging GABAergic inhibitory signaling. It showed efficacy in animal models. & [91, 94, 95, 96, 97] \\ \cline{2-3}  & Anti-inflammatory & It modulates NF-\(\pi\)B and IsRa. & [146] \\ \cline{2-3}  & Antioxidant & It reduces ROS production, caspase-3 activity, MMP and NO activities. & [77, 78, 79, 80, 146] \\ \cline{2-3}  & Antiproliferative & It acts on efflux pumps responsible for multidrug-resistant tumors and on cell cycle arrest via the cyclin-B protein. & [147, 148] \\ \hline \multirow{8}{*}{\(\beta\)-Myvrene} & Anxiolytic, antidepressant & It modulates MAP kinases such as JNK, p38, and it inhibits the synthesis and release of PGE-2.