# Protective Effect of Oyaksoongi-San against Asthma Induced by Ovalbumin in a Mouse Model
## 4 Discussion
Inflammation further amplifies the production of ROS, which alters transcription factor profiles to initiate cellular stress responses [61]. Thus, it is crucial to effectively manage oxidative stress when seeking to improve asthma. In this report, we reveal that OYSGS treatment significantly attenuated oxidative stress in lung tissues, as shown by improvement in the levels of MDA and total glutathione. Regarding potential underlying mechanisms of such effects, a previous study showed that OYSGS inhibits colon cancer cell proliferation by regulating the MAPK pathway [11]. Since the p38 MAPK pathway is known to play a significant role in asthma [43], we hypothesized that OYSGS might influence p38 MAPK. Indeed, we found that mice exposed to ovalbumin exhibited increased p38 MAPK phosphorylation, which has been linked to the elevation of inflammatory factors, such as IL-5 and IL-13, as well as recruitment of neutrophils and lymphocytes. We found that OYSGS appears to mitigate asthma-related inflammatory processes by inhibiting p38 MAPK phosphorylation to downregulate its downstream signaling pathways and thereby decrease pro-inflammatory cytokine levels and inflammatory cell recruitment. Downregulation of IL-5 and IL-13 also contributes to reducing mucus production, as evident from the differences observed in the lung tissue levels of glycoprotein and MUC5 AC. OYSGS is also effective in attenuating oxidative stress, as indicated by improvements in the levels of MDA and total glutathione. One limitation of this study is that we did not address the side effects of the substances comprising OYSGS. For instance, ephedrine, which makes up the second largest portion, has bronchodilator effects but also causes cardiovascular side effects [62; 63]. Narirutin, the third largest component, has anti-inflammatory properties but is known to cause headaches and liver failure [64; 65]. Therefore, further research is needed to understand the comprehensive impact of these side effects. In summary, we have revealed that OYSGS has a protective effect against OVA-induced asthma in mice by reducing inflammation, oxidative stress, and mucus production. These improvements could be related to the inhibition of the p38 MAPK pathway. Although further research is needed to explore the side effects, these findings suggest that OYSGS can be considered a promising candidate for asthma treatment. The following supporting information can be downloaded at [[https://www.mdpi.com/article/10.3390/app14125280/s1](https://www.mdpi.com/article/10.3390/app14125280/s1)]([https://www.mdpi.com/article/10.3390/app14125280/s1](https://www.mdpi.com/article/10.3390/app14125280/s1)), Table S1: Compounds identified in OYSGS by UPLC-DAD-MS/MS. Conceptualization, H.-J.K.; Methodology, E.-J.H., P.K., Y.-J.K. and M.-Y.L. ; Formal Analysis, E.-B.B. and E.-J.H. ; Investigation, J.-Y.S. and E.-B.B. ; Writing and Original Draft, J.-Y.S. and H.-J.K.; Writing, Review, and Editing, H.-J.K. and E.-B.B. ; Supervision, H.-J.K.; Project Administration, H.-J.K.; Funding Acquisition, H.-J.K. All authors have read and agreed to the published version of the manuscript. **Funding:** This research was supported by grants from the Korea Institute of Oriental Medicine (grant number KSN1823221) and Chungnam National University. **Institutional Review Board Statement:** The animal study protocol was approved by the Animal Experimental Ethics Committee of Chungnam National University, 2019012A-CNU-185. **Informed Consent Statement:** Not applicable. **Data Availability Statement:** The data that support the findings of this study are available from the corresponding author upon reasonable request. **Conflicts of Interest:** The authors declare that they have no conflicts of interest.