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

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• 作者：Xiang-Jun Chen ; Bo Zhang ; Shao-Jie Hou ; Yun Shi ; Dun-Quan Xu ; Yan-Xia Wang ; Man-Ling Liu ; Hai-Ying Dong ; Ri-He Sun ; Nan-Di Bao ; Fa-Guang Jin ; Zhi-Chao Li
• 关键词：Acute lung injury ; Osthole ; Nrf2 ; Thioredoxin-1 ; Reactive oxygen species
• 刊名：Respiratory Physiology & Neurobiology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：188
• 期：2
• 页码：214-222
• 全文大小：2247 K

文摘

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.