Li Ying-Peng, Wang Cong-Ying, Shang Hong-Tao, Hu Rui-Rui, Fu Hui, Xiao Xue-Feng
Tianjin University of Traditional Chinese Medicine Tianjin 301617 China
RSC Adv. 2020 May 1;10(29):17101-17113. doi: 10.1039/d0ra00049c. eCollection 2020 Apr 29.
High-throughput lipidomics provides the possibility for the development of new therapeutic drugs. Accordingly, herein, we reveal the protective role of salvianolic acid B (Sal B) in rats with coronary heart disease (CHD) and propose a new mechanism for its action through a high-throughput and non-targeted lipidomics strategy. A CHD animal model was induced by consecutive high-fat diet feeding with vitamin D3 injection. At the end of the 8th week, the serum sample was analyzed to explore the metabolic biomarker and pathway changes using untargeted lipidomics based on ultra-performance liquid chromatography with mass spectrometry (UPLC/MS). In addition, blood and heart tissue samples were collected and processed for the detection of biochemical indicators and liver histological observation. After salvianolic acid B treatment, the levels of LDH, CK, CK-MB, MYO, CTn1, TG, TC, LDL-c, and Apo(b) were significantly lower than that in the model group, while the levels of HDL-c and Apo(a1) were significantly higher than that in the model group. Furthermore, the histological features of fibrosis and steatosis were also evidently relieved in the model group. A total of twenty-six potential biomarkers were identified to express the lipid metabolic turbulence in the CHD animal models, of which twenty-two were regulated by salvianolic acid B trending to the normal state, including TG(20:0/20:4/o-18:0), PC(20:4/18:1(9Z)), PC(18:3/20:2), PA(18:0/18:2), LysoPE(18:2/0:0), SM(d18:0/22:1), PE(22:6/0:0), LysoPE (20:4/0:0), sphinganine, Cer(d18:0/18:0), PS(14:0/14:1), PC (18:0/16:0), LysoPC(17:0), PE(22:2/20:1), PC(20:3/20:4), PE(20:4/P-16:0), PS(20:3/18:0), cholesterol sulfate, TG(15:0/22:6/18:1), prostaglandin E2, arachidonic acid and sphingosine-1-phosphate. According to the metabolite enrichment and pathway analyses, the pharmacological activity of salvianolic acid B on CHD is mainly involved in three vital metabolic pathways including glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism. Thus, based on the lipidomics-guided biochemical analysis of the lipid biomarkers and pathways, Sal B protects against CHD with good therapeutic effect by regulating glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism, inhibiting oxidative stress damage and lipid peroxidation.
高通量脂质组学为新型治疗药物的开发提供了可能性。因此，在本文中，我们揭示了丹酚酸B（Sal B）在冠心病（CHD）大鼠中的保护作用，并通过高通量非靶向脂质组学策略提出了其作用的新机制。通过连续高脂饮食喂养并注射维生素D3诱导建立冠心病动物模型。在第8周结束时，使用基于超高效液相色谱-质谱联用（UPLC/MS）的非靶向脂质组学分析血清样本，以探索代谢生物标志物和通路变化。此外，收集血液和心脏组织样本并进行处理，以检测生化指标并进行肝脏组织学观察。丹酚酸B治疗后，LDH、CK、CK-MB、MYO、CTn1、TG、TC、LDL-c和Apo(b)的水平显著低于模型组，而HDL-c和Apo(a1)的水平显著高于模型组。此外，模型组纤维化和脂肪变性的组织学特征也明显减轻。共鉴定出26种潜在生物标志物以表达冠心病动物模型中的脂质代谢紊乱，其中22种受丹酚酸B调节并趋向于正常状态，包括TG(20:0/20:4/o-18:0)、PC(20:4/18:1(9Z))、PC(18:3/20:2)、PA(18:0/18:2)、LysoPE(18:2/0:0)、SM(d18:0/22:1)、PE(22:6/0:0)、LysoPE (20:4/0:0)、鞘氨醇、Cer(d18:0/18:0)、PS(14:0/14:1)、PC (18:0/16:0)、LysoPC(17:0)、PE(22:2/20:1)、PC(20:3/20:4)、PE(20:4/P-16:0)、PS(20:3/18:0)胆固醇硫酸酯、TG(15:0/22:6/18:1)、前列腺素E2、花生四烯酸和鞘氨醇-1-磷酸。根据代谢物富集和通路分析，丹酚酸B对冠心病的药理活性主要涉及甘油磷脂代谢、鞘脂代谢和花生四烯酸代谢这三个重要代谢途径。因此，基于脂质组学指导的脂质生物标志物和通路的生化分析，Sal B通过调节甘油磷脂代谢、鞘脂代谢和花生四烯酸代谢，抑制氧化应激损伤和脂质过氧化，对冠心病具有良好的治疗保护作用。
