Chang Nianwei, Wang Yu, Jiang Min, Bai Gang
Tianjin University of Traditional Chinese Medicine, Tianjin, China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Evid Based Complement Alternat Med. 2022 Apr 14;2022:2868767. doi: 10.1155/2022/2868767. eCollection 2022.
Chronic cerebral ischemia (CCI) is a pathological condition associated with a variety of cerebrovascular diseases. Shunaoxin pills (SNX) are a traditional Chinese medicine (TCM) used to improve blood circulation. However, its multicomponent and multitarget features make it difficult to decipher the molecular mechanisms.
Thus, in this study, we aimed to identify the key anti-inflammatory components of SNX as markers for standardization and quality control and the potential pharmacological mechanisms of SNX in the treatment of CCI by network pharmacology to provide scientific evidence of its clinical efficacy.
We evaluated the anti-inflammatory effect of SNX using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) combined with a dual-luciferase reporter assay for nuclear factor kappa B (NF-B) inhibition to identify the active components in SNX. In addition, key pathways involved in the anti-inflammatory effect of SNX were predicted using a network pharmacology approach, and some crucial proteins and pathways were further validated by Western blotting.
Shunaoxin pills inhibited NF-B through tumor necrosis factor- (TNF-) stimulation in 293T cells. The therapeutic effect may be related to 10 pathways regulated by ligustilide, ferulic acid, ligustrazine, and senkyunolide I. It was further confirmed that ligustilide could reduce the inflammatory response by inhibiting the phosphorylation of p38 and 3-phosphoinositide-dependent kinase 1 (PDK1).
Ligustilide, senkyunolide I, ferulic acid, and ligustrazine could be used as anti-inflammatory Q-markers to control the quality of SNX, and p38 and PDK1 might be potential targets of SNX in the treatment of CCI.
慢性脑缺血（CCI）是一种与多种脑血管疾病相关的病理状态。舒脑欣滴丸（SNX）是一种用于改善血液循环的中药。然而，其多成分和多靶点的特性使得难以阐明其分子机制。
因此，在本研究中，我们旨在通过网络药理学确定舒脑欣滴丸的关键抗炎成分作为标准化和质量控制的标志物，以及舒脑欣滴丸治疗慢性脑缺血的潜在药理机制，为其临床疗效提供科学依据。
我们使用超高效液相色谱-四极杆飞行时间质谱（UPLC/Q-TOF-MS）结合用于抑制核因子κB（NF-κB）的双荧光素酶报告基因测定来评估舒脑欣滴丸的抗炎作用，以鉴定舒脑欣滴丸中的活性成分。此外，使用网络药理学方法预测舒脑欣滴丸抗炎作用涉及的关键途径，并通过蛋白质免疫印迹进一步验证一些关键蛋白质和途径。
舒脑欣滴丸在293T细胞中通过肿瘤坏死因子-α（TNF-α）刺激抑制NF-κB。治疗效果可能与藁本内酯、阿魏酸、川芎嗪和升麻素苷I调节的10条途径有关。进一步证实，藁本内酯可通过抑制p38和3-磷酸肌醇依赖性蛋白激酶1（PDK1）的磷酸化来减轻炎症反应。
藁本内酯、升麻素苷I、阿魏酸和川芎嗪可作为抗炎Q标志物来控制舒脑欣滴丸的质量，p38和PDK1可能是舒脑欣滴丸治疗慢性脑缺血的潜在靶点。
