## 4 Discussion  
Type 1 diabetes mellitus (T1 DM) is an autoimmune disorder characterized by the immune system's attack on pancreatic beta cells, resulting in hyperglycemia in the host [29]. Currently, there is no cure for T1 DM worldwide, and insulin injection remains the only treatment to manage disease symptoms. STZ, used to induce T1 DM in this experiment, cause beta-cell apoptosis in the pancreas via GLUT2 due to its structural similarity to glucose, thereby impairing insulin production [30]. In this study, T1 DM was induced in rats via the intraperitoneal administration of 30 mg/kg STZ, resulting in hyperglycemia induction (Figure 1) and histological damage (Figure 10), confirming successful T1 DM model induction. The AGEs/ RAGE pathway, known to be crucial in the onset and progression of T1 DM, induces AGE formation in the body when hyperglycemia persists due to diabetes, serving as a major contributor to diabetic complications [15]. RAGE, a member of the immunoglobulin superfamily capable of binding to AGEs, is known to recognize a three-dimensional structure rather than specific amino acid sequences. Prolonged diabetic conditions lead to an increase in AGE levels and RAGE involvement, inducing signaling events through the interaction of AGEs/RAGE, resulting in various downstream effectors, including MAPK-mediated signal transduction [31]. Activation of the MAPK-mediated signaling pathway induces the generation of ROS and upregulates enzymes such as NADPH oxidase and nitric oxide synthase, thereby playing a significant role in the occurrence and prevention of diabetic complications [15]. Consequently, the AGEs/RAGE signaling pathway serves as a crucial mechanism in the pathogenesis and prevention of diabetes and its complication. This study explored the potential effects of CJ on the AGEs/RAGE signaling pathway in an STZ-induced diabetic animal model. In several studies on the activity of compounds in CJ, it has been reported that CJ can influence the inhibition of AGE formation [32], providing assistance in the management of diabetic complications and oxidative stress [33]. STZ-induced rats exhibit polyphagia, polydipsia, and polyuria, leading to weight loss associated with intestine dysfunction, muscle catabolism, and other factors [34; 35; 36]. In our study, the Veh group only lost weight, whereas the CJ-treated groups showed dose-dependent recovery (Table 1). In addition, diabetic rats lose weight and have increased fasting blood glucose levels. These changes contribute to the onset of diabetic complications such as hyperglycemia and lead to the formation of enzymatic immature and mature cross-links and non-enzymatic AGEs. Oxidative stress plays a crucial role in the onset of diabetic complications; therefore, it is essential to regulate intracellular ROS and manage blood glucose levels for effective control [37]. Under oxidative stress-induced diabetic conditions, endogenous antioxidant enzymes [38] and ROS concentrations are regulated by SOD, CAT, and GSH [33]. We investigated the concentration of ROS in liver and kidney tissue samples. In the CJ 100 group, both showed a significant decrease compared with the Veh group (Figures 2A and 3C). In the intricate landscape of cardiovascular physiology, the assertion that NADPH oxidase (NOX) serves as the primary source of ROS highlights the pivotal role this enzyme plays in the delicate balance of oxidative processes within cardiovascular tissues [39]. Our results showed that the expression of NOX-4 and p47 phox was reduced in the CJ100 group compared with that in the Veh group (Figures 4 and 5). In the context of diabetic nephropathy, the expression of NOX-4 within the kidney is intricately linked to the pathophysiology of the condition [40]. Our findings suggest that CJ, through its regulation of ROS induced by diabetes, may act as a key modulator in various pathological conditions associated with increased NADPH oxidase activity in the kidney and liver.