紫草防治血热证的活性成分挖掘与机制探讨

Study on active components and mechanism of shikonin in prevention and treatment of blood heat syndrome

目的在血热证小鼠模型上评价紫草清热机理。方法综合网络药理学方法筛选成药性分子,构建2,4-二硝基苯酚(2,4-Dinitrophenol,DNP)诱导的血热证小鼠模型及高温联合脂多糖(lipopolysaccharide,LPS)诱导的血热证小鼠模型,评价药效并分析关联靶标和相关因子。结果收集紫草素相关靶标277个,主要涉及炎症反应、氧化反应和凝血反应等生物过程。代表化合物紫草素显著改善血热证小鼠的主要证候,降低两种模型炎症因子IL-1β、IL-6和TNF-α水平,减少氧化损伤指标LPO、MDA含量;抑制NF-κB p65的表达,上调Nrf2蛋白是主要作用机制。结论紫草素通过抑制炎症和提高抗氧化能力发挥防治血热证的药理作用,提供了紫草防治血热症的理论依据。

Aim To systematically evaluate the heat-clearing mechanism of Arnebiae Radix on two mouse models of blood heat syndrome.Methods The drug-forming molecules were screened by comprehensive network pharmacology methods,and the correlation between drug efficacy and related factors and targets was evaluated on the mouse model of short effect blood heat syndrome constructed by 2,4-dinitrophenol(DNP)and the mouse model of severe blood heat syndrome(heat stroke)constructed by high temperature combined with lipopolysaccharide(LPS).Results A total of 277 shikonin related targets were collected,mainly involving biological processes such as inflammatory reaction,oxidation reaction and coagulation reaction.Shikonin,a representative compound,significantly improved the main syndromes of mice with blood heat syndrome,reduced the levels of inflammatory factors IL-1β,IL-6 and TNF-α in the two models,and reduced the contents of oxidative damage indexes LPO and MDA,and the two showed correlation.The main mechanism was to inhibit the expression of NF-κB p65 and up-regulate the expression of Nrf2.Conclusions Shikonin plays a pharmacological role in the prevention and treatment of blood heat syndrome by inhibiting inflammation and improving antioxidant capacity,which provides a pharmacological basis for shikonin in the prevention and treatment of blood heat syndrome.