State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
Biomed Pharmacother. 2020 Oct;130:110574. doi: 10.1016/j.biopha.2020.110574. Epub 2020 Jul 30.
The Notoginseng-Safflower pair composed of Panax notoginseng (Burk.) F. H. Chen and Carthamus tinctorius L. has remarkable clinical efficacy for preventing and treating cardiovascular diseases in China. Notoginseng total saponins (NS) and Safflower total flavonoids (SF) are the major effective ingredients in Notoginseng and Safflower, respectively. Though our previous study showed that the combination of NS and SF (NS-SF) exhibits significant cardioprotective effects for myocardial ischemia (MI), there might be difference in their action mechanisms. However, the anti-MI characteristics of individual NS and SF remains unclear. Herein, an integrated metabolomics strategy coupled with multiple biological methods were employed to investigate the cardioprotective effects of NS and SF alone or in combination against isoproterenol (ISO)-induced MI and to further explore the synergistic relationship between NS and SF. Our results demonstrated that pretreatments with NS, SF, and NS-SF all showed cardioprotective effects against MI injury and NS-SF exhibited to be the best. Interestingly, the results demonstrated that NS and SF exhibited differentiated metabolic targets and mediators in the glycerophospholipid metabolism. Furthermore, administration of NS alone exhibited greater effects on reversing the elevated the proinflammatory metabolites and mediators in MI rats compared to SF alone. However, individual SF showed greater amelioration of MI-disturbed antioxidant and prooxidative metabolites and better inhibition of the oxidative stress than NS alone. Collectively, our study demonstrated that the capability of NS-SF to regulate both metabolic targets of NS and SF might be the basis of NS-SF to produce a cooperative effect greater than their individual effects that enhance the anti-MI efficacy and provided valuable information for the clinical application of Notoginseng-Safflower pair.
由三七（Panax notoginseng (Burk.) F. H. Chen）和红花（Carthamus tinctorius L.）组成的三七-红花对在中国预防和治疗心血管疾病具有显著的临床疗效。三七总皂苷（NS）和红花总黄酮（SF）分别是三七和红花的主要有效成分。虽然我们之前的研究表明 NS 和 SF 的组合（NS-SF）对心肌缺血（MI）具有显著的心脏保护作用，但它们的作用机制可能存在差异。然而，单独的 NS 和 SF 的抗 MI 特征尚不清楚。在此，我们采用了一种综合的代谢组学策略，并结合多种生物学方法，研究了 NS 和 SF 单独或联合应用对异丙肾上腺素（ISO）诱导的 MI 的心脏保护作用，并进一步探讨了 NS 和 SF 之间的协同关系。我们的研究结果表明，NS、SF 和 NS-SF 预处理均对 MI 损伤具有心脏保护作用，其中 NS-SF 效果最好。有趣的是，结果表明 NS 和 SF 在甘油磷脂代谢中表现出不同的代谢靶点和介质。此外，与 SF 单独给药相比，NS 单独给药对逆转 MI 大鼠中升高的促炎代谢物和介质表现出更大的效果。然而，与 NS 单独给药相比，SF 单独给药对 MI 紊乱的抗氧化和促氧化代谢物具有更好的改善作用，并且对氧化应激的抑制作用更强。综上所述，我们的研究表明，NS-SF 调节 NS 和 SF 的代谢靶点的能力可能是 NS-SF 产生协同作用的基础，这种协同作用大于它们各自的作用，从而增强抗 MI 疗效，并为三七-红花对的临床应用提供了有价值的信息。
