Luteolin attenuates lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome by activating alveolar epithelial sodium channels via cGMP/PI3K pathway
Copyright © 2021 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:282 |
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| Enthalten in: |
Journal of ethnopharmacology - 282(2022) vom: 10. Jan., Seite 114654 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hou, Yapeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.02.2022 Date Revised 07.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jep.2021.114654 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330792067 |
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| 245 | 1 | 0 | |a Luteolin attenuates lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome by activating alveolar epithelial sodium channels via cGMP/PI3K pathway |
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| 500 | |a Date Completed 07.02.2022 | ||
| 500 | |a Date Revised 07.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute lung injury | |
| 650 | 4 | |a Alveolar fluid clearance | |
| 650 | 4 | |a Epithelial sodium channel | |
| 650 | 4 | |a Luteolin | |
| 650 | 4 | |a cGMP | |
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| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Morpholines |2 NLM | |
| 650 | 7 | |a Sodium Channels |2 NLM | |
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| 700 | 1 | |a Ding, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Hongguang |e verfasserin |4 aut | |
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