Bioactive constituents of Salvia przewalskii and the molecular mechanism of its antihypoxia effects determined using quantitative proteomics

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. This study examined the antihypoxia effects of SPM in vivo. 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. 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 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.高原低压低氧环境可诱导高海拔居住个体产生多种生理及病理应答反应。甘西鼠尾草（Salvia przewalskii Maxim，唇形科，以下简称SPM）是一味传统中药，已知其具备抗菌、抗病毒、抗氧化、抗血栓及抗抑郁等药理活性。本研究旨在体内考察SPM的抗缺氧活性：以SPM干燥粉碎后的根原药材为原料，采用70%乙醇超声提取法制备其提取物；将雄性Sprague-Dawley大鼠随机分为3组，每组10只，分别为正常对照组、低压低氧模型组（模拟海拔4260m）以及低压低氧+SPM给药组（模拟海拔4260m，SPM给药剂量为1.0 g/kg/天），造模与给药周期共计4周。采用肺动脉压记录仪、定量聚合酶链反应及组织病理学分析，分别检测各组大鼠的平均肺动脉压（mean pulmonary arterial pressure, mPAP）、缺氧诱导因子-1α（hypoxia-inducible factor-1α, HIF-1α）mRNA表达水平与肺部组织病理形态；此外，本研究采用基于串联质量标签（tandem mass tag, TMT）的蛋白质组学方法，分析SPM对低压低氧环境下大鼠肺组织蛋白质组的调控作用。实验结果显示，SPM预处理可使大鼠mPAP降低24.86%、HIF-1α mRNA表达水平下调31.24%，并可减轻肺部组织的病理损伤。此外，低氧+SPM给药组大鼠肺组织中共筛选出28个差异表达蛋白（差异倍数>±1.2，p值具有统计学意义）。上述结果表明，SPM是一种极具开发潜力的抗缺氧候选药物，其作用机制可能与增强机体抗氧化能力、抑制果糖代谢通路相关。