# Evaluation of Yukmiijihwang-Tang as a Novel Preventive Agent in Ovalbumin-Induced Murine Asthma
## 4 Discussion
Therefore, managing mucus production is a crucial step in alleviating symptoms and improving overall respiratory function in asthma. Here, we show that the administration of YJT markedly downregulated glycoprotein and MUC5 AC in lung tissues and may, therefore, effectively attenuate asthma-associated mucus production. In asthma, inflammatory cell infiltration and decreases in antioxidant defense lead to the excess generation of ROS, contributing to the onset of oxidative stress [5], which damages tissues and thereby fosters airway inflammation and hyperresponsiveness [5; 47]. The principal antioxidant mechanisms responsible for regulating intracellular ROS involve glutathione [47]. Glutathione predominantly exists in a reduced form (GSH); it provides antioxidant protection by reducing oxidative species, such as ROS, and then undergoing oxidation to SSSG via the enzymatic activity of glutathione peroxidase [5; 47]. Glutathione reductase (GR) employs NADPH to enzymatically convert GSSG back to GSH, thereby initiating a redox cycle. Accordingly, the GSH/GSSG ratio is critical for cellular homeostasis [48]. Under profound oxidative stress, the rate of GSH depletion may surpass that of GSSG generation, resulting in a decrease in the total glutathione level [48]. Under such circumstances, cells endeavor to sustain the GSH/GSSG ratio by increasing GSH synthesis or decreasing GSSG via the action of GR [49]. Here, we report that YJT treatment can reduce the oxidative stress marker MDA while upregulating total glutathione, GSH, and GR. This indicates that YJT effectively attenuates oxidative stress in the context of asthma. The activation of the NF-\(\kappa\)B pathway is very important for the pathophysiology of asthma [30; 50; 51], as this pathway orchestrates many fundamental reactions, including induction of the Th2 response, expression of MUC5 AC in goblet cells, secretion of TNF\(\kappa\) by macrophages, and release of TSLP by endothelial cells. This intricate involvement of NF-\(\kappa\)B signaling underscores its significance as a central regulatory mechanism in the development of asthma. Given a previous report that YJT inhibited the receptor activator of NF-\(\kappa\)B ligand-induced differentiation of osteoclasts [17], we assessed the phosphorylation of NF-\(\kappa\)B in our system. Indeed, our results revealed that YJT significantly reduced the phosphorylation of NF-\(\kappa\)B in the lung tissues of OVA-induced asthmatic mice. Among the component herbal plants of the YJT, geniposidic acid has been shown to reduce inflammation [52], and loganic acid and mornoniside are effective in mitigating both inflammation and oxidative stress [53; 54]. These findings suggest that the therapeutic efficacy of YJT is likely due to the synergistic effects of its individual components. However, the other components of YJT, quercetin and hyperoside, have been reported to have neurotoxicity and nephrotoxicity, respectively [55; 56]. Here, we showed that YJT had no cytotoxicity at concentrations of 0-500 \(\upmu\)g/mL. This is consistent with previous studies showing that YJT has no cytotoxicity at any concentration (-200 \(\upmu\)g/mL) in human urinary bladder cancer cell line T24 and bone marrow macrophages [15; 56]. Furthermore, we previously reported that a 13-week repeated oral administration of aqueous YJT extract in SD rats indicated no toxicity, and the no-observed-adverse-effect level (NOAEL) was found to be 2000 mg/kg/day [57]. However, further research is necessary to elucidate the specific contributions and potential toxic side effects of each component of YJT in vivo. Another limitation of our study is that although YJT significantly reduced the development of OVA-induced asthma in mice, there were no dose-dependent effects of YJT. [PERSON] et al. showed that YJT (200 or 400 mg/kg) effectively inhibited testosterone-inducedbenign prostatic hyperplasia in rats [16]. [PERSON] et al.