Objective To investigate the mechanism of Qingyan Dropping Pills (清咽滴丸, QDP) in alleviating pulmonary inflammation based on NOD-like receptor pyrin domain containing 3 (NLRP3)/cystein-asparate protease-1 (Caspase-1) and p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK) signaling pathways. Methods A total of 50 male Balb/C mice were randomly divided into control group, model group, dexamethasone (5 mg/kg) group, QDP low-, high-dose (0.2, 0.8 g/kg) groups, and mice were intervened with drugs for 7 d. One hour after the last administration, except for the control group, all other mice were induced with lipopolysaccharide (5 mg/kg) to form an acute inflammatory injury model. After 4 h of modeling, serum and lung tissue were collected to calculate the wet dry weight ratio of lung tissue. Levels of interleukin-18 (IL-18), IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in serum were measured by ELISA. Histopathological changes in lung were evaluated by hematoxylin-eosin (HE) staining. Expression of p-p38 MAPK was assessed by immunohistochemistry. Western blotting was employed to analyze protein levels of p-p38 MAPK, p-JNK, Bcl-2-associated X protein (Bax), NLRP3, B-cell lymphoma-3 (Bcl-3), thioredoxin-interacting protein (TXNIP) and Caspase-1 in lung tissue. Reactive oxygen species (ROS) level was evaluated by dihydroethidium (DHE) staining. Pyroptosis level in lung tissue was detected by TUNEL staining. Results Compared with model group, QDP could significantly reduce the wet dry weight ratio of lung tissue in LPS-induced mice (P < 0.05), improve lung injury, significantly down-regulate the levels of IL-18, IL-6, TNF-α and IL-1β in serum (P < 0.05, 0.01), reduce the phosphorylation levels of p38 MAPK and JNK in lung tissue (P < 0.01, 0.001), significantly down-regulate the protein expressions of Bax, NLRP3, Bcl-3, TXNIP and Caspase-1 in lung tissue (P < 0.001), reduce the excessive accumulation of ROS (P < 0.01, 0.001), and inhibit cell apoptosis (P < 0.05, 0.01, 0.001). Conclusion QDP could significantly improve LPS-induced lung inflammation in mice, and its mechanism is related to synergistically exert anti-inflammatory effects by inhibiting NLRP3/Caspase-1 pathway mediated cell apoptosis and p38 MAPK/JNK pathway activation.

Qingyan Dropping Pills (QDP)  /  inflammatory response  /  NLRP3/caspase-1 signaling pathway  /  p38 MAPK/JNK signaling pathway  /  pyroptosis