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6-姜辣素通过上调miR-322-5p抑制脂多糖诱导的RAW264.7细胞炎症反应。

6-Gingerol via overexpression of miR-322-5p impede lipopolysaccharide-caused inflammatory response in RAW264.7 cells.

作者信息

Umar Talha, Yin Baoyi, He Lixin, Feng Wen, Yuan Yongjie, Umer Saqib, Feng Huili, Huang Zhi, Umar Zaima, Liu Wenjing, Ganzhen Deng

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Department of Theriogenology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, 38000, Punjab, Pakistan.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3797-3807. doi: 10.1007/s00210-023-02543-0. Epub 2023 Jun 22.

Abstract

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1β (IL-1β), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.

摘要

急性肺损伤(ALI)和脓毒症是复杂的综合征,在重症患者中常常得不到治疗。6-姜酚是一种存在于新鲜生姜中的酚类植物化学化合物,具有抗炎药理作用。本研究探讨了6-姜酚在脂多糖(LPS)诱导的急性肺损伤小鼠模型和RAW-264.7细胞炎症中的作用。对LPS诱导的动物模型进行组织病理学检查,通过细胞计数试剂盒-8(CCk-8)测定RAW-264.7细胞活力。此外,在体内和体外使用qRT-PCR、免疫荧光、蛋白质印迹和酶联免疫吸附测定法来鉴定与NF-κB和MAPK信号通路相关的炎症因子和蛋白质。在组织学检查中,6-姜酚表现出保护作用。此外,6-姜酚提高了细胞活力,并下调了LPS处理的RAW-264.7细胞中的炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。此外,6-姜酚降低了NF-κB和MAPK途径中P65、P38的磷酸化以及JNK的水平。重要的是,6-姜酚增加了被LPS抑制的miR-322-5p的转录丰度,miR-322-5p的下调抵消了6-姜酚的保护作用。6-姜酚的保护活性是由miR-322-5p的上调介导的。

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