在体内和体外模型中,二萜冠蛋白可减轻脂多糖引起的急性肺损伤。
Diterpene Coronarin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Both In Vivo and In Vitro Models.
发表日期:2023 Oct 31
作者:
Ya Mao, Abdullah A Alarfaj, Samer Hasan Hussein-Al-Ali, Hongxia Ma
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
急性肺损伤(ALI)是由于肺炎、败血症、创伤、误吸、吸入有毒气体和胰腺炎等临床刺激而导致严重的全身炎症反应而发生的临床病症。肺泡屏障的破坏、巨噬细胞的激活、中性粒细胞的浸润和促炎细胞因子是ALI期间发生的重要事件。抑制这些炎症反应的药物可以保护肺部免受炎症损伤。在这项研究中,我们检查了植物化学冠蛋白(一种二萜)的功效,已被证明具有抗炎、抗氧化、抗血管生成和抗肿瘤活性。通过气管内给予LPS诱导健康BALB/c小鼠发生急性肺损伤,然后用5和10mg/kg浓度的冠蛋白处理。估计小鼠的湿/干肺重量以评估肺水肿的诱导。分析 BALF 液的蛋白质浓度和免疫细胞计数。对髓过氧化物酶活性以及趋化因子 MCP-2 和 MIP-2、iNOS、COX-2 和 PGE-2 的水平进行定量,以评估冠蛋白对 LPS 诱导的 ALI 的免疫调节作用。通过测量促炎细胞因子的水平来检查冠蛋白的抗炎特性,并通过肺组织的组织病理学分析得到证实。小鼠 RAW 264.7 细胞用于体外分析。在 LPS 处理的小鼠 RAW 264.7 中使用 MTT 测定评估 Coronarin 的细胞毒性和细胞保护特性。通过评估冠状素处理和未处理的 LPS 诱导细胞中促炎细胞因子的水平,在体外条件下进一步证实了冠状素的抗炎特性。总体而言,我们的体内和体外结果证实冠蛋白显着抑制中性粒细胞的浸润,阻止免疫调节活性和促炎细胞因子的合成,并减轻LPS引起的急性肺损伤。 Coronarin 是一种强效抗炎药,可以进行进一步研究,作为治疗 ALI 的药物。© 2023。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下公司)的独家许可。
Acute lung injury (ALI) is a clinical condition occurs due to severe systemic inflammatory response for clinical stimulus like pneumonia, sepsis, trauma, aspiration, inhalation of toxic gases, and pancreatitis. Disruption of alveolar barriers, activation of macrophages, infiltration of neutrophils, and proinflammatory cytokines are the vital events occurs during ALI. The drugs which inhibit these inflammatory response can protect lungs from inflammatory insults. In this study, we examined the potency of phytochemical coronarin, a diterpene which have been proven to possess anti-inflammatory, antioxidant, antiangiogenic, and antitumor activities. Healthy BALB/c mice were induced to acute lung injury with intra-tracheal administration of LPS and then treated with 5 and 10 mg/kg concentration of coronarin. The wet/dry lung weight of mice were estimated to assess the induction of pulmonary edema. BALF fluid was analyzed for protein concentrations and immune cells count. Myeloperoxidase activity and levels of chemokines MCP-2 and MIP-2, iNOS, COX-2, and PGE-2 were quantified to assess the immunomodulatory effect of coronarin against LPS-induced ALI. The levels of proinflammatory cytokines was measured to examine the anti-inflammatory property of coronarin, and it was confirmed with histopathological analysis of the lung tissue. Murine RAW 264.7 cells were utilized for the in vitro analysis. Cell cytoxicity and cytoprotective property of coronarin was assessed with MTT assay in LPS-treated Murine RAW 264.7. The anti-inflammatory property of coronarin was further confirmed in in vitro condition by estimating the levels of pro-inflammatory cytokines in coronarin-treated and untreated LPS-induced cells. Overall, our in vivo and in vitro results confirm coronarin significantly inhibited the infiltration of neutrophils prevented immunodulatory activity and synthesis of proinflammatory cytokines and alleviated the acute lung injury induced by LPS. Coronarin is a potent anti-inflammatory drug which can be subjected to further research to be prescribed as drug for ALI.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.