Abstract：
Salidroside (SAL) is a natural component derived from Rhodiola rosea 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 in vitro 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)是源自红景天的天然成分,并且以其广泛的生物活性(例如其抗炎和抗氧化性质)而众所周知。然而,其与哮喘相关的作用和作用机制尚未得到很好的探索。近年来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。使用非靶向代谢组学可以更好地了解草药对哮喘的代谢调节机制。本研究旨在阐明SAL的抗哮喘作用及其代谢调控机制。在这项研究中,首先测试了SAL对哮喘小鼠的治疗作用。其次,SAL对气道炎症反应的影响，氧化应激，和气道重塑进行了调查。最后,非靶向代谢组学分析用于探讨SAL对肺代谢产物的影响。结果表明，SAL对哮喘模型小鼠有明显的治疗作用。此外，SAL治疗降低了支气管肺泡灌洗液（BALF）中白介素（IL）-4，IL-5和IL-13的水平，但升高了干扰素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，并降低了甲烷二羧酸醛（MDA）的水平。此外,SAL处理的小鼠显示平滑肌肌动蛋白（α-SMA）的表达降低，基质金属肽酶2（MMP2），基质金属肽酶9（MMP9），和肺中的转化生长因子-β1（TGF-β1）。非靶向代谢组学分析显示肺中31种代谢物受SAL影响。这些代谢产物与嘧啶代谢有关,类固醇激素生物合成，和三羧酸(TCA)循环。总之,SAL治疗可以减轻炎症反应，氧化应激，哮喘模型小鼠的气道重塑。SAL治疗哮喘的机制可能与调节嘧啶代谢有关,类固醇激素生物合成，和TCA循环。进一步的研究可以利用靶向代谢组学和体外模型来深入阐明SAL在调节代谢基础上对哮喘的抗炎和抗氧化机制。
