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基于非靶向代谢组学分析的红景天苷对卵清蛋白诱导的哮喘模型小鼠的作用机制研究

Mechanistic study of salidroside on ovalbumin-induced asthmatic model mice based on untargeted metabolomics analysis.

作者信息

Wang Kun, Wang Li, Zhao Guojing, Liu Yong, Wang Fengchan, Song Huan, Sun Yin, Zhou Zhaoshan, Lu Xuechao, Hu Haibo, Cui Huantian

机构信息

Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital), Qingdao University, China.

Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Shandong, China.

出版信息

Food Funct. 2023 Jan 3;14(1):413-426. doi: 10.1039/d2fo02225g.

DOI:10.1039/d2fo02225g
PMID:36515134
Abstract

Salidroside (SAL) is a natural component derived from and is well known for its wide range of biological activities such as its anti-inflammatory and anti-oxidative properties. However, its effects and mechanisms of action related to asthma have not been well explored yet. Recent studies have found that changes in host metabolism are closely related to the progression of asthma. Many natural components can ameliorate asthma by affecting host metabolism. The use of untargeted metabolomics can allow for a better understanding of the metabolic regulatory mechanisms of herbs on asthma. This study aimed to demonstrate the anti-asthmatic effects and metabolic regulatory mechanisms of SAL. In this study, the therapeutic effects of SAL on asthmatic mice were tested at first. Secondly, the effects of SAL on the airway inflammatory reaction, oxidative stress, and airway remodeling were investigated. Finally, untargeted metabolomics analysis was used to explore the influence of SAL on lung metabolites. The results showed that SAL had a significant therapeutic effect on asthmatic model mice. Moreover, SAL treatment lowered interleukin (IL)-4, IL-5, and IL-13 levels but elevated interferon gamma (IFN-γ) and IL-10 levels in bronchoalveolar lavage fluid (BALF). Additionally, it also increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) levels in the lungs. Besides, SAL-treated mice showed decreased expression of smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), and transforming growth factor-beta 1 (TGF-β1) in the lung. Untargeted metabolomics analysis showed 31 metabolites in the lungs that were influenced by SAL. These metabolites were related to pyrimidine metabolism, steroid hormone biosynthesis, and tricarboxylic acid (TCA) cycle. In conclusion, SAL treatment can reduce the inflammatory response, oxidative stress, and airway remodeling in asthmatic model mice. The mechanism of SAL in the treatment of asthma may be related to the regulation of pyrimidine metabolism, steroid hormone biosynthesis, and the TCA cycle. Further studies can be carried out using targeted metabolomics and models to deeply elucidate the anti-inflammatory and anti-oxidative mechanisms of SAL on asthma based on regulating metabolism.

摘要

红景天苷(SAL)是一种天然成分,具有广泛的生物活性,如抗炎和抗氧化特性。然而,其与哮喘相关的作用和作用机制尚未得到充分研究。最近的研究发现,宿主代谢的变化与哮喘的进展密切相关。许多天然成分可以通过影响宿主代谢来改善哮喘。非靶向代谢组学的应用可以更好地理解草药对哮喘的代谢调节机制。本研究旨在证明SAL的抗哮喘作用和代谢调节机制。在本研究中,首先测试了SAL对哮喘小鼠的治疗效果。其次,研究了SAL对气道炎症反应、氧化应激和气道重塑的影响。最后,采用非靶向代谢组学分析来探讨SAL对肺代谢物的影响。结果表明,SAL对哮喘模型小鼠具有显著的治疗作用。此外,SAL治疗降低了支气管肺泡灌洗液(BALF)中白细胞介素(IL)-4、IL-5和IL-13的水平,但提高了干扰素γ(IFN-γ)和IL-10的水平。此外,它还增加了肺中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性,并降低了丙二醛(MDA)的水平。此外,SAL处理的小鼠肺中平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)和转化生长因子-β1(TGF-β1)的表达降低。非靶向代谢组学分析显示,肺中有31种代谢物受到SAL的影响。这些代谢物与嘧啶代谢、类固醇激素生物合成和三羧酸(TCA)循环有关。总之,SAL治疗可以减轻哮喘模型小鼠的炎症反应、氧化应激和气道重塑。SAL治疗哮喘的机制可能与嘧啶代谢、类固醇激素生物合成和TCA循环的调节有关。可以使用靶向代谢组学和模型进行进一步研究,以基于调节代谢深入阐明SAL对哮喘的抗炎和抗氧化机制。

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