Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Mol Sci. 2023 Mar 10;24(6):5313. doi: 10.3390/ijms24065313.
Safflower (. L) possesses anti-tumor, anti-thrombotic, anti-oxidative, immunoregulatory, and cardio-cerebral protective effects. It is used clinically for the treatment of cardio-cerebrovascular disease in China. This study aimed to investigate the effects and mechanisms of action of safflower extract on myocardial ischemia-reperfusion (MIR) injury in a left anterior descending (LAD)-ligated model based on integrative pharmacology study and ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometer (UPLC-QTOF-MS/MS). Safflower (62.5, 125, 250 mg/kg) was administered immediately before reperfusion. Triphenyl tetrazolium chloride (TTC)/Evans blue, echocardiography, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, lactate dehydrogenase (LDH) ability, and superoxide dismutase (SOD) levels were determined after 24 h of reperfusion. Chemical components were obtained using UPLC-QTOF-MS/MS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze mRNA and protein levels, respectively. Safflower dose-dependently reduced myocardial infarct size, improved cardiac function, decreased LDH levels, and increased SOD levels in C57/BL6 mice. A total of 11 key components and 31 hub targets were filtered based on the network analysis. Comprehensive analysis indicated that safflower alleviated inflammatory effects by downregulating the expression of NFκB1, IL-6, IL-1β, IL-18, TNFα, and MCP-1 and upregulating NFκBia, and markedly increased the expression of phosphorylated PI3K, AKT, PKC, and ERK/2, HIF1α, VEGFA, and BCL2, and decreased the level of BAX and phosphorylated p65. Safflower shows a significant cardioprotective effect by activating multiple inflammation-related signaling pathways, including the NFκB, HIF-1α, MAPK, TNF, and PI3K/AKT signaling pathways. These findings provide valuable insights into the clinical applications of safflower.
红花（. L）具有抗肿瘤、抗血栓、抗氧化、免疫调节和心脑保护作用。临床上用于治疗中国的心脑血管疾病。本研究旨在通过整合药理学研究和超高效液相色谱-四极杆飞行时间串联质谱（UPLC-QTOF-MS/MS），探讨红花提取物对左前降支（LAD）结扎模型心肌缺血再灌注（MIR）损伤的作用及作用机制。红花（62.5、125、250 mg/kg）在再灌注前立即给药。再灌注 24 h 后测定三苯基四氮唑氯（TTC）/伊文思蓝、超声心动图、末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）检测、乳酸脱氢酶（LDH）能力和超氧化物歧化酶（SOD）水平。使用 UPLC-QTOF-MS/MS 获得化学组分。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。采用定量实时聚合酶链反应（qRT-PCR）和 Western blot 分别分析 mRNA 和蛋白水平。红花可剂量依赖性地减少心肌梗死面积，改善心功能，降低 C57/BL6 小鼠 LDH 水平，提高 SOD 水平。基于网络分析共筛选出 11 个关键成分和 31 个枢纽靶点。综合分析表明，红花通过下调 NFκB1、IL-6、IL-1β、IL-18、TNFα和 MCP-1 的表达，上调 NFκBia的表达，显著减轻炎症作用，并显著增加磷酸化 PI3K、AKT、PKC 和 ERK/2、HIF1α、VEGFA 和 BCL2 的表达，降低 BAX 和磷酸化 p65的水平。红花通过激活多个与炎症相关的信号通路，包括 NFκB、HIF-1α、MAPK、TNF 和 PI3K/AKT 信号通路，显示出显著的心脏保护作用。这些发现为红花的临床应用提供了有价值的见解。
