# \(\beta\)-Caryophyllene: A Sesquiterpene with Countless Biological Properties
## 2 Biological properties of \(\beta\)-caryophyllene
### \(\beta\)-Caryophyllene and Nervous System
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Experimental** & **Effects** & **Possible Mechanisms** & **References** \\ \hline
215 and 430 mg/kg/die (p.o.) in rats (model of rheumatoid arthritis) & Reduction of oxidative stress, inflammation and edema & Radical scavenging; Nrf2 induction; Increased glutathione levels; Reduction of the expression of COX-2, cytokines and NF-\(\kappa\)B & [PERSON] et al. (2018) [56] \\ \hline
30 and 300 mg/kg (p.o.) & Reduction of liver & Reduction of cytokineslevels & [PERSON] et al. (2017) [58] \\ in C5/BL/6] mice fed with methionine- and choline-deficient diet (model of non-alcoholic steatohepatitis, NASH) & steatosis, inflammation & Transforming growth factor beta (TGF-\(\beta\)), \\ \hline
30 and 300 mg/kg (p.o.) & Reduction of liver & Reduction of cytokineslevels & [PERSON] et al. (2017) [58] \\ in C5/BL/6] mice fed with methionine- and choline-deficient diet (model of non-alcoholic steatohepatitis, NASH) & & Nox2 and collagen; Increased levels of SOD2 and GPx1 & \\ \hline In the oral cavity for about 10 min & Bactericidal against Streptococcus mutans (tooth decay) & GlucosyltransferaseenseB (GtfB), GtfC and GtfD Inhibition & [PERSON] et al. (2018) [59] \\ \hline
0.1–100 \(\upmu\)M in culture of mouse bone marrow cells & Stimulates osteoblast mineralization and inhibits adipogenesisosis & PPAR-\(\gamma\) activation in pluripotent stem cells; Inhibits TNF-\(\alpha\) and NF-\(\kappa\)B in osteoclasts & [PERSON] et al. (2016) [61] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Cont. (BBB), particularly during mitosis, in which it modulates the filament network, and in the repair following brain injuries [9; 28]. It has been demonstrated that BCP administered intraperitoneally at the dosage of 50 mg/kg, reduces the activation of astrocytes and microglia, by decreasing Iba-1 and GFAP expression, thus avoiding the death of dopaminergic neurons [22]. Amyloid plaques, formed by \(\beta\)-amyloid peptides, composed in turn by 36-43 amino acids and derived from amyloid precursor protein (APP), characterize [PERSON]'s disease. These peptides are responsible for direct toxicity (death of neurons) and indirect toxicity (production of molecules stimulating inflammation). A considerable decrease of the \(\beta\)-amyloid peptide-induced overexpression of TLR4 (Toll-like receptor 4), which determines the activation of monocytes and microglia, has been noted in BV2 microglia cells treated with BCP, and, consequently, the sesquiterpene leads to a clear reduction of the biosynthesis of IL-6, IL-1\(\beta\), PGE2, TNF-\(\alpha\), NF-\(\kappa\)B and nitric oxide. In addition, also a reduced expression of COX-2 and iNOS has been observed [26]. Another common condition affecting central nervous system is Parkinson's disease, a neurodegenerative pathology characterized by neuroinflammation, oxidative stress, mitochondrial dysfunction and cell death, particularly in dopaminergic neurons. An in vitro study on SH-SYSY cells showed that the treatment with BCP inhibits reactive oxygen species (ROS) production, restoring mitochondrial functionality and the levels of the antioxidant glutathione. BCP prevents apoptosis, by inhibiting the expression of Bax and caspase-3 and increasing Bcl-2 one. It reduces the phosphorylation of JNK (c-Jun N-terminal Kinase), which determines the increase of HO-1 (heme oxygenase-1) expression in this pathological condition. All these effects are related to CB2/Nrf2 pathway [29]. Research on a mouse model of [PERSON]'s disease conducted by [PERSON] revealed that the treatment with BCP, at the dose of 10 mg/kg, enhances motor coordination in mice and protects the dopaminergic neurons from degeneration, reducing the production of inflammatory cytokines, in particular IL-1\(\beta\), IL-6, and TNF-\(\alpha\)[30]. BCP is also cytoprotective towards the central nervous system due to its modulation of the redox state and inflammation, useful during chemotherapy.