## 4 Discussion
In the present study, significant reductions in peritoneal and splenic NK cell activity were confirmed in the CPA control group compared to the normal vehicle control group. However, in the AR (100, 200, and 400 mg/kg) groups, a significant increase in peritoneal and splenic NK cell activity was observed in a dose-dependent manner compared to the CPA control group. In particular, 100 mg/kg oral dose of AR showed an inhibitory effect on the reduction in CPA-induced NK cell activity comparable to that of 200 mg/kg of EAP. These results provide clear evidence that, at least under the conditions of this experiment, oral administration of AR (100, 200, and 400 mg/kg) significantly suppresses the decrease in NK cell activity by CPA in a dose-dependent manner, which is comparable to that of EAP (200 mg/kg) in 100 mg/kg oral dose of AR. CPA causes a significant decrease in the number of T lymphocytes, which results in significant atrophy of lymph organs, such as the spleen, lymph nodes, and thymus [11, 13, 16, 30]. Because T-cells always have four types of glycoproteins collectively referred to as antigen receptors, namely CD3, which bind to the surface of cell membranes in an electron noncovalent manner, they are used as surface markers for T-cells [16, 30]. In addition, CD4 is a single-chain glycoprotein with a molecular weight of 55 kDa [60] and is mainly used as a surface marker for helper T-cells and CD8 is a heterodimer where a subunit with a molecular weight of 32-34 kDa is linked with disulfide and is mainly used as a surface marker [61]. The reduction in the spleen of these CD3+, CD8+, and CD4+ cells by CPA administration is well reported [16; 30]. iNOS is induced in various cells by pro-inflammatory substances, such as bacterial LPS, IL-18, TNF-\(\alpha\), and IFN-\(\gamma\). Nitric oxide (NO), which is formed by the oxidation of L-arginine through the action of iNOS, causes various physiological and pathological changes in the living body and induces shock and inflammatory reactions [62]. In addition, as part of immunosuppression by CPA, the reduction in iNOS expression in tissues is well known [30]. In this study, CPA administration resulted in significant atrophy of lymph organs due to a decrease in lymphocytes in the thymus cortex, white medulla of the spleen, and submandibular lymph nodes, and showed a decrease in the number of immunocompetent cells in the spleen tissue including CD3+, CD4+, CD8+, TNF-\(\alpha\)+, IL-18+ and iNOS+ cells. Meanwhile, oral doses of 100, 200, and 400 mg/kg of AR showed a dose-dependent inhibition in the atrophy of the thymus gland, spleen, and submandibular lymph nodes and an increase in the number of immune-competent cells in the spleen tissue, compared to that of the CPA control group. In particular, AR (100 mg/kg) inhibited CPA-induced atrophy in immune organs and reduction in immune-competent cells, comparable to EAP (200 mg/kg). These results provide reliable evidence that oral administration of AR (100, 200, and 400 mg/kg) significantly suppresses spleen and submandibular lymph node atrophy by CPA, at least under the histopathological examination conditions of this experiment, in a dose-dependent manner, showing a suppressing effect comparable to that of EAP (200 mg/kg) in 100 mg/kg oral dose of AR. NF-kB is a protein complex that regulates DNA transcription, cytokine production, and cell survival and is found in almost all cells. NF-kB plays an important role in the body's defense response to various stimuli, such as stress, cytokines, free radicals, heavy metals, ultraviolet rays, oxidized LDL, bacteria, and viruses [63; 64]. In particular, NF-kB plays an important role in immune regulation in the body's defense against infection and provides a component of the \(\times\) light chain of antibodies [65; 66]. NF-kB is the most important protein that regulates the transcription of various genes involved in innate and acquired immune responses [67].