Yang Ke, Luo Yun, Lu Shan, Hu Ruifeng, Du Yuyang, Liao Ping, Sun Guibo, Sun Xiaobo
Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing, China.
Front Pharmacol. 2018 Jun 20;9:662. doi: 10.3389/fphar.2018.00662. eCollection 2018.
Salvianolic acid B (SalB) and ginsenoside Re (Re) protect endotheliocytes against apoptosis through different mechanisms. However, whether both compounds could synergistically protect endothelial cells against oxidized low-density lipoprotein (Ox-LDL)-induced apoptosis is unclear. This study aimed to assess the protective effect of combined SalB and Re (SR) treatment on Ox-LDL-induced endothelial apoptosis and to explore the mechanism underlying this effect. Results showed that SalB, Re, or SR could protect against Ox-LDL-induced endothelial apoptosis. Furthermore, the composition of SR was optimized through central composite design with response surface methodology. SR with a composition of 60 μg/mL of SalB and 120 μg/mL of Re exerted the optimal protective effect. Network pharmacology research revealed that SalB and Re in SR synergistically protect against Ox-LDL-induced endothelial apoptosis by regulating oxidative stress and phlogistic pathways. experiments confirmed these results. Compared with the same dose of SalB or Re alone, SR significantly decreased the contents of inflammatory mediators and increased the activities of antioxidant enzymes. SR could synergistically restore the balanced redox state of the cells and inhibit the activation of nuclear transcription factor kappa B and the caspase cascade by activating the phosphatidylinositol 3 kinase/protein kinase B pathway and inhibiting the phosphorylation of p38 mitogen-activated protein kinase. These pathways are regulated by down-regulating the expression of lectin-like Ox-LDL receptor-1 and NADPH oxidase and up-regulating the expression of estrogen receptor alpha. Therefore, SR effectively prevents Ox-LDL-induced endothelial apoptosis through antioxidative and antiinflammatory mechanisms.
丹酚酸B(SalB)和人参皂苷Re(Re)通过不同机制保护内皮细胞免受凋亡。然而,这两种化合物是否能协同保护内皮细胞免受氧化型低密度脂蛋白(Ox-LDL)诱导的凋亡尚不清楚。本研究旨在评估SalB和Re联合(SR)处理对Ox-LDL诱导的内皮细胞凋亡的保护作用,并探讨其作用机制。结果表明,SalB、Re或SR均可保护细胞免受Ox-LDL诱导的内皮细胞凋亡。此外,采用中心复合设计和响应面法对SR的组成进行了优化。SalB浓度为60μg/mL、Re浓度为120μg/mL的SR具有最佳保护效果。网络药理学研究表明,SR中的SalB和Re通过调节氧化应激和炎症途径协同保护细胞免受Ox-LDL诱导的内皮细胞凋亡。实验证实了这些结果。与相同剂量的SalB或Re单独使用相比,SR显著降低了炎症介质的含量,增加了抗氧化酶的活性。SR可协同恢复细胞的氧化还原平衡状态,通过激活磷脂酰肌醇3激酶/蛋白激酶B途径并抑制p38丝裂原活化蛋白激酶的磷酸化,抑制核转录因子κB的激活和半胱天冬酶级联反应。这些途径通过下调凝集素样Ox-LDL受体-1和NADPH氧化酶的表达以及上调雌激素受体α的表达来调节。因此,SR通过抗氧化和抗炎机制有效预防Ox-LDL诱导的内皮细胞凋亡。
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