The process of ALI is associated with excessive pulmonary inflammation as undue activation of immune cells including macrophages and neutrophile granulocytes and subsequently increased cytokines such as interleukin 6 (IL-6) contribute to severe tissue damage and irreversible pulmonary pathological changes. NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome is a cytosolic receptor consisting of upstream sensor protein NLRP3, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and the effector protein caspase-1. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that neutralizes oxidative stress via initiating antioxidant response element-driven gene transcription. Nrf2 is suppressed by kelch-like ECH-associated protein 1 (Keap1) under physiological conditions, while Nrf2 dissociates from Keap1, stabilizes and accumulates in the nucleus with stimulation of oxidative stress. Thereafter, heme oxygenase 1 (HO-1) a downstream target gene of Nrf2 is activated to catalyze various detoxification reactions and exert anti-oxidative capacity.
ISO significantly promoted the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and down-regulated kelch-like ECH-associated protein 1 (Keap1). Simultaneously, it suppressed the over-expression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin IL-1β (pro-IL-1β), and inhibited the expression of apoptotic related proteins induced by LPS challenge. Meanwhile, the results of molecular docking indicated the potential ability of ISO as a ligand binding with proteins Keap1, NLRP3 and cleaved-caspase-3 as well.

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) usually result in significant mortality and are featured by pulmonary edema, dysregulated inflammation, and alveolar/capillary barrier destruction. ALI is derived from various lung injuries such as severe pulmonary infection, near drowning, lung contusion, and pulmonary embolism. Methods: This research work was supported by the National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province. LPS (from Escherichia coli O55:B5) was purchased from Sigma (St. Louis, MO, USA). Dexamethasone (DEX) was supplied by Shenyang Guangda Pharmaceutical Co., Ltd. The SOD, NO, MPO, and IL-6 assay kits were obtained from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). The identification was performed by Professor Tserendulam Luvsandorj at the Mongolian University of Pharmaceutical Science and specimens were preserved in the School of Traditional Chinese Pharmacy, China Pharmaceutical University. TML was soaked with water for 30 min and decoction three times was conducted with the solid-liquid ratio of 1:10, 1:8, and 1:6, respectively. ICR male mice (8 weeks old, 22–25 g) were purchased from Henan Sikes’s Biotechnology Co., Ltd (Henan, China). Statistical tests were performed using IBM SPSS Statistics version 26.0 Software (SPSS, Inc., Chicago, IL, USA) and presented as mean ± standard deviation for continuous variables. Conclusion In summary, the effect of TML on acute lung injury has been studied with Isoorientin, one of its biologically active compounds. Studies have demonstrated that Isoorientin has been shown to protect against pulmonary edema, inflammatory cells, and inflammatory cytokine mediator expression in acute lung injury caused by LPS. Therefore, we have a certain need to study the mechanisms by which this protective effect takes place further.