## 4 Discussion
This implies a potential regulatory role for CJ in diverse pathologies related to diabetic complications, hinting at its significance as a major regulator in conditions characterized by heightened oxidative stress in renal and hepatic tissues. We evaluated serum creatinine and BUN levels (Table 2). Creatinine, a major product of muscle metabolism, is excreted by the kidney and serves as an important indicator of renal function [41]. Elevated creatinine levels are often associated with renal failure. Ourresults showed that the administration of CJ restored the levels of creatinine and BUN, indicating that CJ may help manage renal failure. According to various studies, the binding of AGEs and RAGE induces the activation of the p38 MAPK pathway [7]. This activation is implicated in processes such as cell death and is particularly activated in the renal cortex. MAPK is a member of the protein kinase family, composed of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38, which collectively regulate extracellular signaling [42; 43]. In the results of this study, the injection of STZ was found to impact the phosphorylation of MAPK markers in the liver and kidney of rats, confirming the induction of MAPK pathway activation. This indicates that STZ injection induces the activation of MAPK pathway, which in turn can influence the secretion of inflammatory mediators such as proinflammatory cytokines. In our study, the administration of CJ was observed to inhibit the activation of p38, ERK1/2 and JNK in the liver. Furthermore, it was found to be effective in regulating p38 and ERK1/2 levels in the kidney. Notably, the CJ 100 group exhibited a significant decrease compared with the Veh group. These results suggest that CJ can control MAPK activation under STZ-induced diabetic condition. AGE accumulation can lead to vascular damage and RAGE overexpression in smooth muscle and endothelial cells [44]. In this study, we observed a significant increase in RAGE expression in the liver and kidneys of rats injected with STZ alone compared with the Normal group rats. RAGE expression appeared to be regulated by various factors, with one of the most significant being the accumulation of AGEs. Therefore, the reduced RAGE expression in STZ-induced rats treated with CJ may be attributed, as suggested by other studies, to a probable decrease in AGEs accumulation. The interaction between AGEs and cell receptor is known to play a crucial role in the development of complications associated with diabetes [45; 46]. AGEs accumulate in various diabetic complication-prone areas such as the kidney and retina [46; 47]. They act as stimuli, activating intracellular signaling pathway and modifying the function of intracellular proteins. In particular, among various complications induced by diabetes, AGEs in hyperglycemia elevate intracellular oxidative stress, contributing to the initiation of other complications [48]. This ultimately contributes to inflammatory mechanisms such as MAPK and NF-\(\kappa\)B activation [7]. The interaction between AGEs and RAGE in macrophage cells induces the activation of the MAPK pathway [49]. This activation subsequently triggers NF-\(\kappa\)B, leading to the modulation of the production of inflammatory cytokines such as tumor necrosis factor (TNF)-\(\alpha\), interleukin(IL)-1\(\alpha\), and IL-6 [50]. In addition, it contributes to the enhancement of ROS generation [46]. Therefore, inhibiting the formation of AGEs could contribute to the regulation of various oxidative stress and inflammatory mediators, suggesting a novel approach to diabetes treatment beyond glucose control alone. In summary, we have shown that CJ extracts in STZ-induced diabetic rats can inhibit AGEs/ RAGE levels, followed by oxidative stress and MAPK pathway activation. Taken together, our results suggest that under STZ-induced diabetic conditions, administration of CJ may reduce the expression of AGEs factors and RAGE in liver and kidney tissues, thereby potentially controlling the AGEs/ RAGE pathway.