## 4 Discussion
The results of this study indicate that the IAP extract administration dose-dependently inhibits the PM\({}_{2.5}\)-induced oxidative stress and inflammatory lung damage via antioxidant and anti-inflammatory activities by the reduction of p38 MAPK, NF-\(\kappa\)B, and PI3K/Akt expression. MMPs are a group of structurally similar endopeptidases [93]. MMPs play an important role in tumor invasion, tissue morphogenesis, skin aging, angiogenesis, arthritis, and tissue repair, as they cause the degradation of various extracellular matrices [94; 95]. MMPs can be subdivided into collagen-degrading enzymes, gelatinases, matrix-lysine enzymes, membranous MMPs, and various other types according to their structural characteristics and substrates [96; 97]. PM\({}_{2.5}\) increases the expression of various MMPs, especially MMP-9 and MMP-12, as part of an inflammatory response, destroying the parenchyma of the surrounding respiratory system and causing respiratory distress through airway damage [16; 93; 98; 99]. In this experiment, there were significant increases in MMP-9 and -12 levels in the lung tissue of the PM\({}_{2.5}\) control group compared to the normal vehicle control group. However, in contrast, the levels of MMP-9 and -12 in the lung tissue of all IAP-extract-administered groups were significantly reduced in a dose-dependent manner. Notably, the IAP400 group exhibited similar levels of MMP-9 and MMP-12 in PM\({}_{2.5}\)-induced lung tissue compared to the DEXA group. These findings indicate that oral administration of IAP extract can effectively mitigate PM\({}_{2.5}\)-induced airway damage in a dose-dependent manner by reducing MMP-9 and MMP-12 expression. Indeed, excessive ROS imposes oxidative stress on proteins and lipids within the mitochondrial membrane, leading to severe damage. This damage may include loss of membrane potential, increased membrane permeability, and release of cytochrome c [100], activating caspase-3 and mitochondria-dependent apoptosis [101]. Oxidative stress caused by PM\({}_{2.5}\) induces mitochondria-dependent apoptosis [102]. Exactly, in the context of mitochondria-dependent apoptosis, Bax and Bcl-2 serve as representative pro-apoptotic and anti-apoptotic proteins, respectively. Bax plays a critical role in this process by inducing the loss of mitochondrial membrane potential, leading to the activation of caspase-3 and the release of cytochrome c, ultimately triggering apoptosis [103]. Exposure to PM\({}_{2.5}\) affects a rise in Bax expression and a decrease in Bcl-2 expression [16; 100; 101]. In this experiment, the expression of apoptosis-related Bcl-2 mRNA was significantly decreased, and the expression of Bax mRNA was significantly increased in the lung tissue of the PM\({}_{2.5}\) control group compared to the normal vehicle control group. On the other hand, the expression of Bcl-2 mRNA was increased, and the expression of Bax mRNA was decreased in the lung tissue of all three IAP-extract-administered mice, in a dose-dependent manner. In particular, Bcl-2 and Bax mRNA expression in PM\({}_{2.5}\)-induced lung tissue was comparable between the IAP400 and DEXA groups. These results show that the oral administration of IAP extract can dose-dependently suppress lung damage caused by PM\({}_{2.5}\)-induced apoptosis by regulating Bax and Bcl-2 mRNA expression. The air space area (ASA; %/mm\({}^{2}\)) could act as an indirect indicator to measure the gas exchange capacity histomorphometrically. A reduction in gas exchange surface area decreases ASA, indicating a decrease in lung function. In several lung diseases, a decrease in ASA has been noticed histopathologicalally [16; 34; 49; 104]. PAS staining is a classic histochemical technique utilized to selectively stain mucus-secreting cells. An increase in PASstaining indicates heightened activity of mucus-producing cells [16; 105; 106].