## 4 Antimicrobial Activity of _C. japonica_ EO in Food Industry and Human Diseases  
EOs are generally accepted as natural antimicrobials and antioxidants that can be used in the food industry as bio-preservatives to increase shelf life and quality of food products [49]. In addition, infections caused by fungi and bacteria represent a key issue due to the development of resistant species to current fungicides and antibiotics. Therefore, EOs could be an ecological and effective alternative to synthetic antimicrobial agents [49]. Table 3 shows the antimicrobial activity of _C. japonica_ EO from different tissues and geographical origins, against several gram-positive and gram-negative bacterial strains, as well as against various fungal species. The minimal inhibitory concentrations (MICs) were determined by the broth dilution method. [PERSON] et al. [37] reported that EO from leaves of South Korean _C. japonica_ has excellent antimicrobial activity against several oral bacteria, except _Escherichia coli_, with MICs ranging from 0.025 to 12.8 mg/mL (Table 3). According to the authors, this activity is mainly due to the presence of \(\alpha\)-pinene, sabinene, \(\alpha\)-terpineol and 4-terpineol compounds. In fact, the major chemical group of the studied EO is the monoterpene hydrocarbons (highly lipophilic), which possibly possess cytotoxicity by the disruption of bacteria membrane integrity. On the other hand, [PERSON] et al. [50] showed that EO from needles and twigs of South Korean _C. japonica_ had weak antibacterial activity, namely against gram-negative bacteria, with MICs greater than 10 mg/mL (Table 3). Similar findings have already been reported for heartwood components of _C. japonica_[51]. The observed discrepancy between the two referred studies can be attributed to the influence of the plant organ on the EO chemical composition. However, it is known that gram-negative bacteria have an outer membrane, rich in lipopolysaccharidesaccharides, which acts as a permeability barrier against hydrophobic molecules, hence it is expected that EOs are less effective against gram-negative than gram-positive bacteria. Nevertheless, it is worth noting that EOs could also be cytotoxic to eukaryotic cell membranes [52]. Therefore, further studies are needed with respect to both target and non-target organisms. Oppositely, in the [PERSON] et al. [50] study, _C. japonica_ EO (which is ent-kaurene type) exhibited antifungal activity against fungal strains that cause foot rot and other human diseases, namely against _Cryptococcus neoformans_ (Table 3). Contrary to the leaves, twigs or heartwood are rich in sesquiterpene hydrocarbons, namely \(\delta\)-cadinene, which is associated with superior antifungal activities [10; 53]. In fact, [PERSON] et al. [10] showed that the heartwood EO of _C. japonica_ from Taiwan, which is rich in sesquiterpene hydrocarbons, has the strongest antifungal activity against wood decay and tree pathogenic fungi, followed by leaf EO. This activity was associated mainly with \(\delta\)-cadinene, the major compound in the EO. Therefore, EO from _C. japonica_ could also have applications in timber industry as natural wood preservatives. Moreover, in [PERSON] et al. [53] study, the EO from the heartwood of Japanese _C. japonica_ inhibited the growth of _Trichophyton rubrum_, while no antibacterial activity was observed with respect to _Staphylococcus epidermidis_ (Table 3), possibly due to the lack of monoterpene hydrocarbons, as the authors stated. Contrary to heartwood EO, leaf EO of _C. japonica_, which is rich in monoterpene hydrocarbons, is highly active against this gram-positive strain [37; 38] (Table 3). Furthermore, diterpenoids [54] and diterpenes in EO from _C. japonica_ leaves can also affect microbes that cause skin [38] and human diseases, such as tuberculosis [32]. However, these last authors were more restrictive as considering EOs with MIC > 0.250 mg/mL as inactive (Table 3). Yet, _C.