Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1

Autor: Xiangjun Chen, Yanxia Wang, Dun-Quan Xu, Faguang Jin, Zhichao Li, Hai-Ying Dong, Shao-Jie Hou, Ri-He Sun, Nan-Di Bao, Bo Zhang, Yun Shi, Man-Ling Liu
Rok vydání: 2013
Předmět:
Lipopolysaccharides
Male
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
Time Factors
Lipopolysaccharide
Cell Survival
NF-E2-Related Factor 2
Physiology
Acute Lung Injury
Pharmacology
Lung injury
Transfection
Statistics
Nonparametric
Flow cytometry
Mice
chemistry.chemical_compound
Thioredoxins
Western blot
Coumarins
In vivo
medicine
Animals
RNA
Messenger
RNA
Small Interfering
Cell Line
Transformed
chemistry.chemical_classification
Mice
Inbred BALB C
Reactive oxygen species
Dose-Response Relationship
Drug
medicine.diagnostic_test
business.industry
General Neuroscience
Organ Size
respiratory system
Calcium Channel Blockers
Survival Analysis
Up-Regulation
respiratory tract diseases
Reverse transcription polymerase chain reaction
Disease Models
Animal
Oxidative Stress
Bronchoalveolar lavage
chemistry
Reactive Oxygen Species
business
Bronchoalveolar Lavage Fluid
Zdroj: Respiratory Physiology & Neurobiology. 188:214-222
ISSN: 1569-9048
Popis: Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.
Databáze: OpenAIRE
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