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提取物对卵清蛋白诱导的哮喘大鼠炎症和肺氧化损伤的减轻作用:抗氧化潜力、信号转导和转录激活因子6(STAT6)及肿瘤坏死因子(TNF)通路的计算机模拟和体内联合研究

Attenuation of ovalbumin-induced inflammation and lung oxidative injury in asthmatic rats by extract: combined in silico and in vivo study on antioxidant potential, STAT6 and TNF- pathways.

作者信息

Jedli Olfa, Ben-Nasr Hmed, Zammel Nourhène, Rebai Tarek, Saoudi Mongi, Elkahoui Salem, Jamal Arshad, Siddiqui Arif J, Sulieman Abdelmoneim E, Alreshidi Mousa M, Naïli Houcine, Badraoui Riadh

机构信息

Laboratory of Histo-Embryology & Cytogenetics, Medicine Faculty of Sfax, University of Sfax, Magida Boulila Street, 3029 Sfax, Tunisia.

Laboratory of Pharmacology, Medicine Faculty of Sfax, University of Sfax, Majida Boulila Street, 3029 Sfax, Tunisia.

出版信息

3 Biotech. 2022 Sep;12(9):191. doi: 10.1007/s13205-022-03249-5. Epub 2022 Jul 26.

Abstract

In the present study we focused on the anti-asthmatic and antioxidant effects of L. (ZO) aqueous extract. This study includes 20 adult male rats, which were grouped into four; Group I: control group; Group II: asthmatic group (Ovalbumin sensitized/challenge model, Oval group); Group III: received ovalbumin sensitized/challenge associated a dose of 207 mg/kg body weight (BW) of ZO (Oval + D1 group); Group IV: received ovalbumin sensitized/challenge associated a dose of 414 mg/k BW of ZO (Oval + D2 group). After 21 days, blood and lung samples were collected for biochemical, hematological, and histopathological analyses. The ameliorative effect of ZO phytochemical compounds was also assessed by in silico approach on transducer and activator of transcription 6 (STAT6) and tumor necrosis factor- (TNF-) receptors. The oxidative/antioxidative status was evaluated in the lung tissues. Our results show that ZO extract alleviated the ovalbumin-induced hematological and biochemical disruptions associated oxidative injury. In fact, white and red blood cells (WBC and RBC, respectively), aspartate aminotransaminase (ASAT), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) were significantly disrupted ( < 0.05) in Oval group and alleviated following ZO treatment. Besides, several histopathological features were outlined in lung tissues of Oval group. Interestingly, ZO was found to exert ameliorative effects on tissue level. In silico analyses, particularly the binding affinities, the number of H-bonds, the embedding distance and the molecular interactions of ZO phytochemical compounds with either STAT6 or TNF- supported the in vivo results. These findings confirm the potential ethno-pharmacological effects of ZO against asthma and its associated complications.

摘要

在本研究中,我们聚焦于L. (ZO)水提取物的抗哮喘和抗氧化作用。本研究包括20只成年雄性大鼠,将其分为四组;第一组:对照组;第二组:哮喘组(卵清蛋白致敏/激发模型,卵清蛋白组);第三组:接受卵清蛋白致敏/激发并给予207毫克/千克体重的ZO剂量(卵清蛋白+ D1组);第四组:接受卵清蛋白致敏/激发并给予414毫克/千克体重的ZO剂量(卵清蛋白+ D2组)。21天后,采集血液和肺组织样本进行生化、血液学和组织病理学分析。还通过计算机模拟方法评估了ZO植物化学化合物对转录信号调节因子6 (STAT6)和肿瘤坏死因子- (TNF-)受体的改善作用。在肺组织中评估氧化/抗氧化状态。我们的结果表明,ZO提取物减轻了卵清蛋白诱导的与氧化损伤相关的血液学和生化紊乱。事实上,卵清蛋白组中白细胞和红细胞(分别为WBC和RBC)、天冬氨酸转氨酶(ASAT)、丙二醛(MDA)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GPx)显著紊乱(P < 0.05),而ZO治疗后有所缓解。此外,卵清蛋白组的肺组织呈现出几种组织病理学特征。有趣的是,发现ZO在组织水平上发挥了改善作用。计算机模拟分析,特别是ZO植物化学化合物与STAT6或TNF-的结合亲和力、氢键数量、嵌入距离和分子相互作用,支持了体内实验结果。这些发现证实了ZO对哮喘及其相关并发症潜在的民族药理学作用。

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