Guorao Wu1,2, Ting Yuan1,3, He Zhu1, Huilan Zhang1,2, Jiakun Su4, Lei Guo4, Qing Zhou1, Fei Xiong1, Qilin Yu1, Ping Yang1, Shu Zhang1, Biwen Mo3, Jianping Zhao2, Jibao Cai4, Cong-Yi Wang1. 1. The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China. 2. Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology 1095 Jiefang Ave, Wuhan 430030, China. 3. Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guilin Medical University 15 Lequn Road, Guilin, Guangxi, China. 4. China Tobacco Jiangxi Industrial Co., Ltd. Nanchang High Technology Development Valley, Nanchang 330096, China.
Abstract
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by the persistent airflow obstruction. Chrysophanol, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, has been reported to be protective for some inflammatory diseases. The present report aimed to dissect its effect on cigarette smoke extract (CSE)-induced apoptosis in 16HBECs, a human bronchial epithelial cell line. METHODS: CCK8 cell viability assay was conducted to evaluate the protective effect of chrysophanol on 16HBECs after CSE induction. Western blot analysis, Annexin V/PI staining and TUNEL assay were conducted to test the effect of chrysophanol on 16HBECs apoptosis induced by CSE. Then the western blot assay measured associated molecular pathways to dissect the mechanisms underlying protective effect of chrysophanol on 16HBECs. RESULTS: Chrysophanol protects 16HBECs against CSE-induced apoptosis in a dose dependent manner. Specifically, pre-treatment of 16HBECs with 20 mmol/l of chrysophanol, reduced CSE-induced apoptosis by almost 10%. Mechanistically, chrysophanol manifested high potency to attenuate CSE-induced expression of apoptotic markers, Bax and cleaved caspase 3. In particular, chrysophanol not only represses CSE-induced oxidative stress by inhibiting CYP1A1 expression, but also suppresses CSE-induced ER stress by inhibiting pPERK, ATF4 and ATF6 expression. CONCLUSION: Chrysophanol showed protective effect on CSE-induced epithelial injuries in cell line 16HBECs. And our data support that chrysophanol could be employed to reduce the toxicity of cigarette smoke in bronchial epithelial cells, which may have the potential to decrease the risk for developing COPD in smoking subjects. IJMEG
OBJECTIVE:Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by the persistent airflow obstruction. Chrysophanol, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, has been reported to be protective for some inflammatory diseases. The present report aimed to dissect its effect on cigarette smoke extract (CSE)-induced apoptosis in 16HBECs, a human bronchial epithelial cell line. METHODS: CCK8 cell viability assay was conducted to evaluate the protective effect of chrysophanol on 16HBECs after CSE induction. Western blot analysis, Annexin V/PI staining and TUNEL assay were conducted to test the effect of chrysophanol on 16HBECs apoptosis induced by CSE. Then the western blot assay measured associated molecular pathways to dissect the mechanisms underlying protective effect of chrysophanol on 16HBECs. RESULTS:Chrysophanol protects 16HBECs against CSE-induced apoptosis in a dose dependent manner. Specifically, pre-treatment of 16HBECs with 20 mmol/l of chrysophanol, reduced CSE-induced apoptosis by almost 10%. Mechanistically, chrysophanol manifested high potency to attenuate CSE-induced expression of apoptotic markers, Bax and cleaved caspase 3. In particular, chrysophanol not only represses CSE-induced oxidative stress by inhibiting CYP1A1 expression, but also suppresses CSE-induced ER stress by inhibiting pPERK, ATF4 and ATF6 expression. CONCLUSION:Chrysophanol showed protective effect on CSE-induced epithelial injuries in cell line 16HBECs. And our data support that chrysophanol could be employed to reduce the toxicity of cigarette smoke in bronchial epithelial cells, which may have the potential to decrease the risk for developing COPD in smoking subjects. IJMEG
Authors: Li Tao; Jianmei Xie; Yuting Wang; Shi Wang; Shuangchan Wu; Qiman Wang; Hong Ding Journal: Bioorg Med Chem Lett Date: 2014-12-01 Impact factor: 2.823