## 4 Discussion  
_C. albicans_ colonizes mucous membranes and can act as an etiological factor in opportunistic infection, which can lead to life-threatening mucosal infections in immunosuppressed patients [32]. The local factors of oral candidiasis include oral cancer, dentures, decreased salivary gland function, and the use of steroids. The systemic factors include age, smoking, diabetes, Cushing syndrome, decreased immunity, malignant tumors, malnutrition, and antibiotics [19]. Topical local antifungal treatments, such as clotrimazole and nystatin, are used to treat _C. albicans_. However, clotrimazole has a risk of causing dental caries with its high sugar content, and in many cases with nystatin, the treatment is unsuccessful due to limitations such as oral structure (tongue, palate, gingva, and teeth) and saliva dilution [33]. Among other things, the most important drawbacks of these antifungal agents are suboptimal selectivity, increased toxicity, and increased likelihood of developing resistance. In particular, although amphoteric B is considered the \"standard\" for antifungal therapy, it is intrinsically toxic because it lacks selectivity, given that fungi and mammalian cells are eukaryotic and share many similar biological processes [34]. The newest class of antifungals and the first fungi-specific antifungals are represented by echinocandins (caspofungins), which target key components of the fungal cell wall that are not present in mammalian cells. Unfortunately, the clinical use of echinocandins is limited to the treatment of systemic candidiasis, and the emergence of resistance in _C. glabrata_ is of particular concern [35]. Therefore, natural mouthwash ingredients are actively researched to treat _C. albicans_. _C. obtusa_ belongs to the Cupressaceae family and is native to Japan. It was introduced to South Korea in the early 20 th century and is now naturalized in the central and southern regions of the country [36]. Antioxidant materials are extensively researched in various ways due to their safe and natural active-oxygen scavenging activity [37]. This study investigated the antioxidant activity of _C. obtusa_. As a result, the MIC value of COE preventing the visible growth of _C. albicans_ was 10 mg/mL, while the MBC value was 30 mg/mL for _C. albicans_. According to [PERSON]'s report, when 0.2% chlorhexidine mouthwash was used against _C. albicans_, the MIC was 12.5%, confirming that _C. obtusa_ was more effective against _C. albicans_ than chlorhexidine, which is widely used worldwide. Also, Arrowash liquid mouthrinse containing three herbs (Cadila Pharmaceuticals, Cadila Pharmaceutical Ltd. Ahmedabad, Gujarat, India) also reported MBC at 50%, suggesting the possibility of using the COE-containing mouthwash used in this study [38]. Polyphenolic compounds are the secondary metabolites that are widely distributed in plants and contain two or more phenolic hydroxyl (-OH) groups in one molecule, which easily combine with various compounds. It has been reported that polyphenic compounds have various physiological activities, including antioxidant, antimicrobial, anticancer, anti-inflammatory, and antidiabetic [39]. Furthermore, flavonoids are known to assist in antioxidant activity, platelet aggregation inhibition, and anti-inflammatory and  
Figure 4: Survival rate of HaCaT cell growth treated with COE. anticancer activities [40]. The higher the total amounts of polyphenols and flavonoids, the higher the antioxidant activity, indicating a positive correlation. In this study, the polyphenol and flavonoid contents in COE were measured as 424.150 mg GAE/g and 127.566 mg CE/g, respectively. Compared to the polyphenol contained in the ethanol-extracted sea buckthorn leaf, which is reported to be 285.64 mg GAE/g [41], the total polyphenol amount from COE measured in this study was 1.49 times higher. Furthermore, the total flavonoid amount in this study was 2.13 times higher than the other research result, which reported 58.84 \(\pm\) 0.47 mg CE/g in ethanol-extracted artichoke extract [42].