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 |
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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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