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表没食子儿茶素没食子酸酯通过调控 Keap1/Nrf2 信号通路改善卵清蛋白诱导的哮喘小鼠的生理、免疫和组织病理学改变。

Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway.

机构信息

Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt.

Zoology Department, Faculty of Science, Sirte University, Sirte 128123, Libya.

出版信息

Mar Drugs. 2023 Aug 18;21(8):455. doi: 10.3390/md21080455.

DOI:10.3390/md21080455
PMID:37623736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10455754/
Abstract

Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups ( = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1β (IL-1β). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome's therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway.

摘要

哮喘是一种以氧化应激、气道重塑和炎症为特征的慢性支气管炎症性疾病。Echinochrome(Ech)是一种具有抗氧化和抗炎活性的深紫红色色素。在这项研究中,我们旨在研究 Ech 对哮喘小鼠炎症、氧化应激和脾、肝、肾组织病理学改变的影响。将小鼠分为四组(每组 8 只):对照组、哮喘组和腹腔注射 0.1 和 1mg/kg Ech 的哮喘组。体外研究结果证实了 Ech 的抗氧化和抗炎活性。Ech 通过降低血清免疫球蛋白 E(IgE)、白细胞介素 4(IL-4)和白细胞介素 1β(IL-1β)水平发挥抗哮喘作用。它通过降低肝脏、脾脏和肾脏中丙二醛(MDA)和一氧化氮(NO)含量,增加还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、谷胱甘肽-S-转移酶(GST)和过氧化氢酶(CAT)来减轻氧化应激。此外,它通过增加总蛋白和白蛋白并降低天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、肌酐、尿素和尿酸水平来保护哮喘引起的肝肾功能障碍。此外,它还改善了肺、肝、脾和肾的组织病理学异常。此外,还进行了分子对接研究,以检查 Ech 和 Kelch-like ECH-associated protein 1(Keap1)之间的相互作用。PCR 和 Western blot 分析证实了 Ech 与 Keap1 的结合,以及 Ech 在肝脏、脾脏和肾脏中 Keap1-(核因子红细胞 2 相关因子 2)Nrf2 信号通路中的调节作用。根据我们的研究结果,Ech 可预防脾、肝、肾的哮喘及其并发症。抑制炎症和氧化应激是 Ech 通过调节 Keap1/Nrf2 信号通路来治疗哮喘的两种作用机制。

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