Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Chin J Nat Med. 2022 Aug;20(8):601-613. doi: 10.1016/S1875-5364(22)60186-9.
Vascular endothelial cells and oxidation reduction system play an important role in the pathogenesis of atherosclerosis (AS). If these conditions are disordered, it will inevitably lead to plaque formation and even rupture. Astragaloside IV (AsIV) and salvianolic acid B (Sal B) are the main active ingredients of Astragalus membranaceus and Salvia miltiorrhiza, respectively, and found to ameliorate vascular endothelial dysfunction and protect against oxidative stress in recent studies. However, it is still unknown if the combination of AsIV and Sal B (AsIV + Sal B) can inhibit the development of plaque through amplifying the protective effect of vascular endothelial cells and anti-oxidative stress effect. To clarify the role of AsIV + Sal B in AS, we observed the efficacy of each group (Control, Model, AsIV, Sal B, and AsIV + Sal B) by biomolecular assays, such as observing the pathological morphology of the aorta by oil red O staining, evaluating the level of oxidative stress and endothelial cells in the serum by the Elisa test, and analyzing the changes of all small molecule metabolites in liver tissue by UPLC-QTOF-MS. Results showed that AsIV, Sal B and AsIV + Sal B decreased the deposition of lipid in the arterial wall, so as to exert the effect of anti-oxidant stress and vascular endothelial protection, where the inhibitory effect of AsIV + Sal B was the most obvious. Metabonomics analysis showed that Sal B regulated the metabolic pathways of arginine and proline. AsIV regulated glycerol metabolism and saturated fatty acid biosynthesis metabolism. AsIV + Sal B is mainly related to the regulation of the citrate cycle (TCA cycle), alanine, aspartic acid, and glutamate metabolism, cysteine, and methionine metabolism. Succinic acid and methionine are synergistic metabolites that exert an enhancing effect when AsIV and Sal B were used in combination. In conclusion, we demonstrated that AsIV acompanied with Sal B can be successfully used for anti-oxidative stress and vascular endothelial protection of AS, and succinic acid and methionine are the synergistic metabolites.
血管内皮细胞和氧化还原系统在动脉粥样硬化（AS）的发病机制中起着重要作用。如果这些情况发生紊乱，将不可避免地导致斑块形成甚至破裂。黄芪甲苷（AsIV）和丹参素 B（Sal B）分别是黄芪和丹参的主要活性成分，最近的研究发现它们可以改善血管内皮功能障碍并抵抗氧化应激。然而，目前尚不清楚 AsIV 和 Sal B 的联合应用（AsIV+Sal B）是否可以通过放大血管内皮细胞的保护作用和抗氧化应激作用来抑制斑块的发展。为了阐明 AsIV+Sal B 在 AS 中的作用，我们通过生物分子检测等方法观察了各组（对照组、模型组、AsIV 组、Sal B 组和 AsIV+Sal B 组）的疗效，如油红 O 染色观察主动脉的病理形态，Elisa 试验评估血清中的氧化应激和内皮细胞水平，以及 UPLC-QTOF-MS 分析肝组织中小分子代谢物的变化。结果表明，AsIV、Sal B 和 AsIV+Sal B 减少了动脉壁中脂质的沉积，从而发挥抗氧化应激和血管内皮保护作用，其中 AsIV+Sal B 的抑制作用最为明显。代谢组学分析表明，Sal B 调节了精氨酸和脯氨酸的代谢途径。AsIV 调节甘油代谢和饱和脂肪酸生物合成代谢。AsIV+Sal B 主要与柠檬酸循环（TCA 循环）、丙氨酸、天冬氨酸和谷氨酸代谢、半胱氨酸和蛋氨酸代谢的调节有关。琥珀酸和蛋氨酸是协同代谢物，当 AsIV 和 Sal B 联合使用时会发挥增强作用。综上所述，我们证明了 AsIV 联合 Sal B 可成功用于 AS 的抗氧化应激和血管内皮保护，琥珀酸和蛋氨酸是协同代谢物。
