Bioactive constituents of Salvia przewalskii and the molecular mechanism of its antihypoxia effects determined using quantitative proteomics
Bioactive constituents of Salvia przewalskii and the molecular mechanism of its antihypoxia effects determined using quantitative proteomics
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DOI：
10.1080/13880209.2020.1762668
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Wu, Xinan
中科院分区：
文献类型：
--
作者：
Wang, Yafeng;Duo, Delong;Wu, Xinan
研究背景：高海拔地区的环境低压缺氧可诱导机体产生多种生理或病理反应。甘西鼠尾草（Salvia przewalskii Maxim（Labibii））是一种传统的中草药，具有抗菌、抗病毒、抗氧化、抗血栓形成和抗血栓形成等活性。目的：研究SPM在体内的抗缺氧作用。材料与方法：采用70%乙醇超声提取法，对丹参药材进行干燥、粉碎。雄性Sprague-Dawley大鼠分为3组（n = 10）：正常组、低氧组（海拔4260 m）和低氧+ SPM组（海拔4260 m，SPM 1.0 g/kg/d）。实验持续4周。采用肺动脉压记录仪、定量聚合酶链反应和组织病理学分析平均肺动脉压（mPAP）、缺氧诱导因子-1 α（HIF-1 α）mRNA和肺病理学。此外，利用基于TMT的蛋白质组学方法观察了SPM对缺氧时肺蛋白质组的影响。结果：SPM预处理可降低mPAP（24.86%）和HIF-1 α（31.24%），减轻肺组织病理改变。另外，缺氧+ SPM组中共有28个蛋白质在肺中差异表达（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有关，如Adh 7，Cyp 2d 1，Plod 2，Selenow，ND 3和Fabp 1的表达下调所证明的，以及果糖代谢，如Khk和Aldob的表达下调所证明的。讨论与结论：这些结果表明，SPM是一种很有前途的抗缺氧药物。其作用机制可能与提高抗氧化能力和抑制果糖代谢有关。
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-1 alpha (HIF-1 alpha) 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-1 alpha (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.