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Salvinorin A protects against methicillin resistant staphylococcus aureus-induced acute lung injury via Nrf2 pathway.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2021 Jan; Vol. 90, pp. 107221. Date of Electronic Publication: 2020 Dec 03. - Publication Year :
- 2021
-
Abstract
- Salvinorin A (SA), a neoclerodane diterpene, is isolated from the dried leaves ofSalvia divinorum. SA has traditionally been used treatments for chronic pain diseases. Recent research has demonstrated that SA possesses the anti-inflammatory property. The present study aim to explore the effects and potentialmechanisms ofSA in protection against Methicillin Resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI). Here, we firstly found that verylowdosesof SA (50 μg/kg) could markedly decrease the infiltration of pulmonary neutrophils, mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and then attenuated ALI cause by MRSA infection in mice. In vitro findings revealed that SA attenuated lipoteichoicacid-induced apoptosis, inflammation and oxidative stress in RAW264.7 cells. Mechanism research revealed that SA increased both mRNA levels and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulated mRNA expression of its downstream genes (HO-1, Gclm, Trx-1, SOD1 and SOD2). Additionally, Nrf2 knockout mice abolished the inhibitory effect of SA on neutrophil accumulation and oxidative stress in MRSA-induced ALI. In conclusion, SA attenuates MRSA-induced ALI via Nrf2 signaling pathways.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Acute Lung Injury metabolism
Acute Lung Injury microbiology
Acute Lung Injury pathology
Animals
Cytokines metabolism
Disease Models, Animal
Inflammation Mediators metabolism
Lung metabolism
Lung microbiology
Lung pathology
Macrophages drug effects
Macrophages metabolism
Macrophages microbiology
Macrophages pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2-Related Factor 2 genetics
Neutrophil Infiltration drug effects
Oxidative Stress drug effects
Pneumonia, Staphylococcal metabolism
Pneumonia, Staphylococcal microbiology
Pneumonia, Staphylococcal pathology
RAW 264.7 Cells
Signal Transduction
Acute Lung Injury prevention & control
Anti-Inflammatory Agents pharmacology
Diterpenes, Clerodane pharmacology
Lung drug effects
Methicillin-Resistant Staphylococcus aureus pathogenicity
NF-E2-Related Factor 2 metabolism
Pneumonia, Staphylococcal prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 90
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33293260
- Full Text :
- https://doi.org/10.1016/j.intimp.2020.107221