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山奈酚通过抑制MAPKs和IL-6/STAT3信号通路改善脂多糖诱导的急性肺损伤。

Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways.

作者信息

Chen I-Chen, Wang Shu-Chi, Chen Yi-Ting, Tseng Hsin-Han, Liu Po-Len, Lin Tzu-Chieh, Wu Hsin-En, Chen Yuan-Ru, Tseng Yu-Hsin, Hsu Jong-Hau, Dai Zen-Kong, Suen Jau-Ling, Li Chia-Yang

机构信息

Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.

Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

出版信息

Pharmaceuticals (Basel). 2021 Oct 14;14(10):1046. doi: 10.3390/ph14101046.

Abstract

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of L. and has been reported to have anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.

摘要

急性肺损伤(ALI)是一种伴有急性炎症的高致死率疾病。紫铆因是从豆科植物中分离得到的一种化合物,据报道具有抗炎活性。在此,我们研究了紫铆因在体外和体内对脂多糖(LPS)诱导的ALI的治疗潜力。通过酶联免疫吸附测定(ELISA)分析促炎细胞因子分泌水平;使用蛋白质免疫印迹法检测炎症相关蛋白的表达;分别通过多色流式细胞术检测支气管肺泡灌洗液(BALF)中的免疫细胞浸润数量,并通过苏木精-伊红(HE)染色检测肺组织中的免疫细胞浸润数量。实验结果表明,紫铆因可减轻LPS诱导的人支气管上皮细胞(HBEC3-KT细胞)中白细胞介素-6(IL-6)的产生。在气管内注射LPS诱导的ALI小鼠中,紫铆因减轻了组织损伤,抑制了炎症细胞浸润,并降低了BALF和血清中IL-6和肿瘤坏死因子-α(TNF-α)的分泌。此外,它还进一步抑制了丝裂原活化蛋白激酶(MAPK)的磷酸化,包括磷酸化c-Jun氨基末端激酶(p-JNK)、磷酸化细胞外信号调节激酶(p-ERK)、磷酸化p38(p-p38),并抑制了肺中信号转导和转录激活因子3(STAT3)的激活。总的来说,我们的结果首次证明了紫铆因对LPS诱导的ALI具有抗炎作用,并表明紫铆因作为一种新型ALI治疗药物具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64fe/8537250/e9fa988e8701/pharmaceuticals-14-01046-g001.jpg

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