Key Lab of New Animal Drug Project of Gansu Province, Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, China.
Front Immunol. 2022 Jul 29;13:939106. doi: 10.3389/fimmu.2022.939106. eCollection 2022.
Aspirin eugenol ester (AEE) was a novel drug compound with aspirin and eugenol esterified. AEE had various pharmacological activities, such as anti-inflammatory, antipyretic, analgesic, anti-oxidative stress and so on. In this study, it was aimed to investigate the effect of AEE on the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. experiments evaluated the protective effect of AEE on the LPS-induced A549 cells. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured in the cell supernatant. The Wistar rats were randomly divided into five groups (= 8): control group, model group (LPS group), LPS + AEE group (AEE, 54 mg·kg), LPS + AEE group (AEE, 108 mg·kg), LPS + AEE group (AEE, 216 mg·kg). The lung wet-to-dry weight (W/D) ratio and immune organ index were calculated. WBCs were counted in bronchoalveolar lavage fluid (BALF) and total protein concentration was measured. Hematoxylin-Eosin (HE) staining of lung tissue was performed. Glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), antioxidant superoxide dismutase (SOD), total antioxidant capacity (T-AOC), lactate dehydrogenase (LDH), C-reactive protein (CRP), myeloperoxidase (MPO), malondialdehyde (MDA), macrophage mobility inhibitory factor (MIF), TNF-α, IL-6, and IL-1β activity were measured. The metabolomic analysis of rat serum was performed by UPLC-QTOF-MS/MS. From the results, compared with LPS group, AEE improved histopathological changes, reduced MDA, CRP, MPO, MDA, and MIF production, decreased WBC count and total protein content in BALF, pro-inflammatory cytokine levels, immune organ index and lung wet-dry weight (W/D), increased antioxidant enzyme activity, in a dose-dependent manner. The results of serum metabolomic analysis showed that the LPS-induced ALI caused metabolic disorders and oxidative stress in rats, while AEE could ameliorate it to some extent. Therefore, AEE could alleviate LPS-induced ALI in rats by regulating abnormal inflammatory responses, slowing down oxidative stress, and modulating energy metabolism.
阿司匹林丁香酚酯（AEE）是一种新型药物化合物，由阿司匹林和丁香酚酯化而成。AEE 具有多种药理活性，如抗炎、解热、镇痛、抗氧化应激等。本研究旨在探讨 AEE 对脂多糖（LPS）诱导的大鼠急性肺损伤（ALI）的影响。实验评估了 AEE 对 LPS 诱导的 A549 细胞的保护作用。测定细胞上清液中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的含量。将 Wistar 大鼠随机分为五组（每组 n=8）：对照组、模型组（LPS 组）、LPS+AEE 组（AEE，54mg·kg）、LPS+AEE 组（AEE，108mg·kg）、LPS+AEE 组（AEE，216mg·kg）。计算肺湿重/干重（W/D）比和免疫器官指数。计数支气管肺泡灌洗液（BALF）中的白细胞数并测定总蛋白浓度。进行肺组织苏木精-伊红（HE）染色。测定谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）、抗氧化超氧化物歧化酶（SOD）、总抗氧化能力（T-AOC）、乳酸脱氢酶（LDH）、C 反应蛋白（CRP）、髓过氧化物酶（MPO）、丙二醛（MDA）、巨噬细胞移动抑制因子（MIF）、TNF-α、IL-6 和 IL-1β 活性。采用 UPLC-QTOF-MS/MS 进行大鼠血清代谢组学分析。结果显示，与 LPS 组相比，AEE 改善了组织病理学变化，降低了 MDA、CRP、MPO、MDA 和 MIF 的产生，降低了 BALF 中白细胞计数和总蛋白含量，降低了促炎细胞因子水平、免疫器官指数和肺湿重/干重（W/D），并呈剂量依赖性增加了抗氧化酶活性。血清代谢组学分析结果表明，LPS 诱导的 ALI 导致大鼠代谢紊乱和氧化应激，而 AEE 可在一定程度上改善这种情况。因此，AEE 可通过调节异常炎症反应、减缓氧化应激和调节能量代谢来减轻 LPS 诱导的大鼠 ALI。
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