1. Luteolin attenuates lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome by activating alveolar epithelial sodium channels via cGMP/PI3K pathway.
- Author
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Hou Y, Li J, Ding Y, Cui Y, and Nie H
- Subjects
- Animals, Chromones pharmacology, Cyclic GMP antagonists & inhibitors, Cyclic GMP genetics, Cyclic GMP metabolism, Gene Expression Regulation drug effects, Lung Injury chemically induced, Male, Mice, Mice, Inbred BALB C, Morpholines pharmacology, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Random Allocation, Respiratory Distress Syndrome chemically induced, Up-Regulation drug effects, Alveolar Epithelial Cells drug effects, Lipopolysaccharides toxicity, Lung Injury drug therapy, Luteolin therapeutic use, Respiratory Distress Syndrome drug therapy, Sodium Channels metabolism
- Abstract
Ethnopharmacological Relevance: Luteolin (Lut) was recently identified as the major active ingredient of Mosla scabra, which was a typical representative traditional Chinese medicine and had been used to treat pulmonary diseases for thousands of years., Aim of the Study: This study was to explore the effects and relative mechanisms of Lut in LPS-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The main characteristic of ALI/ARDS is pulmonary edema, and epithelial sodium channel (ENaC) is a key factor in effective removal of excessive alveolar edematous fluid, which is essential for repairing gas exchange and minimizing damage to the peripheral tissues. However, whether the therapeutic effects of Lut on respiratory diseases are relative with ENaC is still unknown., Materials and Methods: Alveolar fluid clearance was calculated in BALB/c mice and ENaC function was measured in H441 cells. Moreover, ENaC membrane protein and mRNA were detected by Western blot and real-time PCR, respectively. We also studied the involvement of cGMP/PI3K pathway during the regulation of Lut on ENaC during LPS-induced ALI/ARDS by ELISA method and applying cGMP/PI3K inhibitors/siRNA., Results: The beneficial effects of Lut in ALI/ARDS were evidenced by the alleviation of pulmonary edema, and enhancement of both amiloride-sensitive alveolar fluid clearance and short-circuit currents. Lut could alleviate the LPS decreased expression levels of ENaC mRNA and membrane protein in H441 cells and mouse lung. In addition, cGMP concentration was increased after the administration of Lut in ALI/ARDS mice, while the inhibition of cGMP/PI3K pathway could abrogate the enhanced AFC and ENaC protein expression of Lut., Conclusion: These results implied that Lut could attenuate pulmonary edema via enhancing the abundance of membrane ENaC at least partially through the cGMP/PI3K pathway, which could provide a promising therapeutic strategy for treating ALI/ARDS., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2022
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