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Bioactive constituents of Salvia przewalskii and the molecular mechanism of its antihypoxia effects determined using quantitative proteomics
Pharmaceutical Biology ( IF 3.8 ) Pub Date : 2020-01-01 , DOI: 10.1080/13880209.2020.1762668
Yafeng Wang 1 , Delong Duo 1 , Yingjun Yan 1 , Rongyue He 1 , Shengbiao Wang 1 , Aixia Wang 1 , Xinan Wu 2
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Abstract Context: Environmental hypobaric hypoxia induces several physiological or pathological responses in individuals in high-altitude regions. Salvia przewalskii Maxim (Labiatae) (SPM) is a traditional Chinese herbal medicine and has known antibacterial, antiviral, antioxidant, anti-thrombotic, and anti-depressant activities. Objective: This study examined the antihypoxia effects of SPM in vivo. Materials and methods: The dried and pulverised of SPM was extracted from root crude drug with 70% ethanol with ultrasound. Male Sprague-Dawley rats were divided into three groups (n = 10): normal group, hypoxia group (altitude of 4260 m), and hypoxia + SPM group (altitude of 4260 m, SPM of 1.0 g/kg/day). The experiment persisted for 4 weeks. The mean pulmonary arterial pressure (mPAP), hypoxia-inducible factor-1α (HIF-1α) mRNA, and lung pathology were analysed using pulmonary artery pressure recorder, quantitative polymerase chain reaction, and histopathological analysis. Moreover, the effects of SPM on lung proteomes during hypoxia were observed by a TMT-based proteomic approach. Results: Pre-treatment with SPM decreased mPAP (24.86%) and HIF-1α (31.24%), and attenuated the pathological changes in lung tissues. In addition, a total of 28 proteins were differentially expressed in lung of hypoxia + SPM group (fold change > ± 1.2 and p < 0.05). The differentially altered proteins were primarily associated with antioxidative stress, as evidenced by the downregulated expression of Adh7, Cyp2d1, Plod2, Selenow, ND3, and Fabp1, and fructose metabolism, as evidenced by the downregulated expression of Khk and Aldob. Discussion and conclusions: These results suggested that SPM is a promising drug for antihypoxia. The mechanism of action might be related to increasing antioxidant capacity and inhibiting fructose metabolism.

中文翻译:

普氏鼠尾草的生物活性成分及其抗缺氧作用的分子机制利用定量蛋白质组学确定

摘要背景:环境低压缺氧会引起高海拔地区个体的多种生理或病理反应。Salvia przewalskii Maxim (Labiatae) (SPM) 是一种传统的中草药,具有抗菌、抗病毒、抗氧化、抗血栓形成和抗抑郁活性。目的:本研究检验了 SPM 在体内的抗缺氧作用。材料与方法:用70%乙醇超声从根生药中提取干燥粉碎的SPM。雄性Sprague-Dawley大鼠分为3组(n=10):正常组、缺氧组(海拔4260 m)、缺氧+SPM组(海拔4260 m,SPM 1.0 g/kg/day)。实验持续了4周。平均肺动脉压 (mPAP)、缺氧诱导因子-1α (HIF-1α) mRNA、使用肺动脉压力记录仪、定量聚合酶链反应和组织病理学分析对肺病理和肺病理进行分析。此外,通过基于 TMT 的蛋白质组学方法观察了 SPM 对缺氧期间肺蛋白质组的影响。结果:SPM预处理降低了mPAP(24.86%)和HIF-1α(31.24%),减轻了肺组织的病理变化。此外,共有28种蛋白质在缺氧+SPM组肺中差异表达(倍数变化> ± 1.2和p < 0.05)。差异改变的蛋白质主要与抗氧化应激相关,如 Adh7、Cyp2d1、Plod2、Selenow、ND3 和 Fabp1 的下调表达以及果糖代谢所证明,如 Khk 和 Aldob 的下调表达所证明。讨论和结论:这些结果表明 SPM 是一种有前景的抗缺氧药物。其作用机制可能与增加抗氧化能力和抑制果糖代谢有关。
更新日期:2020-01-01
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