## 4 Discussion  
Due to the increase in the incidence of PM-induced respiratory diseases, an alternative method for treating or preventing respiratory damage caused by PM has become necessary. In this context, the PM\({}_{2.5}\)-induced lung injury model using BALB/c mouse has shown pathologies similar to human PM-induced respiratory diseases [1; 2; 3; 16]. Therefore, in the present study, the dose-dependent lung damage improvement effects of IAP extract were evaluated using a PM\({}_{2.5}\)-induced mouse lung injury model to find new candidates for natural drugs and functional foods that can improve lung health [1; 2; 3; 16]. Significant weight loss is a well-known side effect of DEXA [16; 34; 48; 49]. In this study, significant weight loss in the DEXA-supplied group at 7 and 8 days was noticed in  
Figure 7: Representative and general histopathological profiles of the lung tissues taken from vehicle or PM\({}_{2.5}\)-treated pulmonary-injured mice. ASA = Alveolar surface area; PAS = Periodic acid Schiff. sB = Secondary bronchus; pB = Primary bronchiole; TA = Terminal respiratory bronchiole-alveoli. (**A**) = vehicle control (DW PO (per oral) with saline). (**B**) = PM\({}_{2.5}\) control (DW PO with PM\({}_{2.5}\)). (**C**) = DEXA (0.75 mg/kg of DEXA PO with PM\({}_{2.5}\)). (**D**) = IAP400 (400 mg/kg of IAP PO mice with PM\({}_{2.5}\)). (**E**) = IAP200 (200 mg/kg of IAP PO with PM\({}_{2.5}\)). (**F**) = IAP100 (100 mg/kg of IAP PO with PM\({}_{2.5}\)). Scale bars = 200 \(\upmu\)m; arrows indicated PAS-positive mucus-producing cells. comparison with the normal vehicle and PM\({}_{2.5}\) control groups, respectively. Furthermore, compared to the normal vehicle and PM\({}_{2.5}\) control groups during the 10-day administration period, there was a significant decrease in B.W. and weight gain. On the other hand, in comparison with the PM\({}_{2.5}\) and vehicle control groups, the weight gain and B.W. were not significantly changed in any of the three IAP-extract-administered groups, and the animal weight was similar to that of BALB/c mice of the identical age [50; 51]. AST and ALT have been used as representative blood biochemical indicators to determine liver damage [52]. No significant difference in the amount of serum AST and ALT levels was noticed between the vehicle control group and the PM\({}_{2.5}\)-induced lung injury experimental groups. Moreover, no significant differences in serum AST and ALT levels were noticed in DEXA, IAP400, IAP200, and IAP100 groups. All experimental mice, including the PM\({}_{2.5}\) control group, showed changes in serum AST and ALT levels within the normal range for male BALB/c mice of the same age [50; 51; 52]. Hence, the current findings indicate that two intranasal injections of PM\({}_{2.5}\) (1 mg/kg) 48 h apart or repeated oral administration of DEXA (0.75 mg/kg) or IAP (400, 200, or 100 mg/kg) one time each day during 10 days does not cause serious liver toxicity in mice. Lung weight is commonly used as an indicator for observing pulmonary edema as a result of vascular leakage [16; 34; 53]. Similar to the ovalbumin-induced asthma model [54; 55] in PM\({}_{2.5}\)-induced mice, as part of the inflammatory response, the vascular endothelial cells' binding force can weaken, resulting in pulmonary edema as an effect of vascular leakage increase [2; 3; 16]. Following intranasal injection of PM\({}_{2.5}\), lung enlargement with pronounced local congestion, indicating pulmonary edema, was noted, and significant increases in gross congestion and absolute and relative lung weights were observed compared to the normal vehicle control group. Nevertheless, in all IAP-extract-administered groups, significant reductions in pulmonary congestion (visibly observed) and lung weights (relative and absolute) were observed in a dose-dependent manner. Particularly, PM\({}_{2.5}\)-induced lung blockage, weight gain (relative and absolute), and lung enlargement were comparable between the IAP400 and DEXA groups.