## 4 Discussion
The induced mice showed an up-regulation of inflammatory Th-2 mediated signal molecules in serum and nasal fluid as previously reported [4,27]. We used the Balb/C mouse to induce allergic rhinitis because, according to a previous study, inflammation reactions are better expressed in Balb/C mice than in other mice models. Moreover, [PERSON] et al. reported that the Balb/C mouse model is recommended to use to study related to Th-2 response inflammation or allergic study [28,29]. Dexamethasone, used as a positive control, showed alleviated effect against inflammation induced by OVA. According to [PERSON] et al. [4], dexamethasone suppressed the cytokine level such as IL-4 and immunocytes such as eosinophils, and we also used it as a positive agent [4]. Th-2 cytokines induce inflammatory reactions, such as immunocyte activation and production of IgE as well as epithelial-derived cytokines [30,31]. In our analysis, serum IgE, IL-4, TNF, and IL-5 were decreased significantly in CIAR administrated group. Further, TSLP, IL-24, and IL-33 levels were also reduced post-CIAR administration in OVA-induced mice. Induced allergic rhinitis with OVA is resulted in high levels of Th-2 signal expression in nasal fluid, as reported previously [32]. Similarly, CIAR administration effectively inhibited Th-2 inflammatory cytokines and related signal molecules in nasal fluid in a dose manner. But unlike serum, IL-5 cytokine level change was not observed in nasal fluid. This may be due to immunocytes change, which is observed in serum but not in nasal fluid, and according to [PERSON] et al., it has been reported that high IL-5 increases in allergic rhinitis patients with increased immune cells such as eosinophils and neutrophils [33]. Additionally, according to [PERSON] et al., immunocytes were not observed in mouse nasal fluid [4]. Therefore, IL-5 was not observed in mouse nasal fluid where immune cells were not counted. Previous studies reported increased thickness of the nasal mucosal tissue of mice induced by OVA [34,35]. Th-2 cells activated with OVA secrete IL-4 or IL-5 cytokine, which stimulates B cells, eosinophils, basophils, and mast cells. The subsequent production of IgE, IL-33, IL-25, and TSLP mediators induce degranulation of effector cells results in nasal epithelial damage and thickening [36]. As depicted in Figure 3, the thickened nasal epithelium was alleviated to a thickness of 36.78 \(\pm\) 2.25, 26.28 \(\pm\) 3.09, and 22.72 \(\pm\) 1.23 from 53.26 \(\pm\) 1.96 \(\upmu\)m when administered with CIAR at doses of 150 mg/kg, 300 mg/kg, and 450 mg/kg, respectively. In addition, we confirmed the inhibitory effects of CIAR, CI, and AR on Th-2 signaling pathways in-vitro on Raw264.7 and RBL-2H3 cells. The lRaw264.7 macrophage cells and RBL-2H3 basophil cells upregulated production of IL-4, IL-33, TNF, and TSLP on stimulation with LPS or A23187, respectively, as previously reported [16,37,38,39]. Treatment of these cells by CI and AR extracts suppressed the stimulation of these signal molecules. Moreover, the inhibitory effect of these extracts on the TH-2 signaling pathway was synergistic when used together (CIAR). To guess the reason for the synergic effect of mixed CI and AR showed, we analyzed the phytochemicals or bioactive components with HPLC or amino acids analyzer. As previously reported, organic acids, flavonoids, or amino acids have many functional effects, especially anti-inflammation [40,41]. As we tabulated in Table 2, AR contains more amino acid contents than CI, such as Ile and Leu, which have already been reported to have anti-inflammatory effects [42,43]. Interestingly, the analysis results of organic acids showed different patterns. As shown in Table 3, CI contains more organic acids contents than AR, such as succinic acid, tartaric acid, and butyric acid, which are also reported to have anti-inflammatory functions [44,45]. Therefore, we carefully considered this point as one of the reasons for synergic effects.