一品红(EL)是一种传统的有毒草药,用于治疗水肿,腹水,闭经,无尿和便秘。降低EL毒性的处理对于其安全有效的应用至关重要。然而,关于EL处理后降低毒性的分子机制知之甚少。本研究旨在筛选EL和PEL的差异标记,探讨EL和处理后EL(PEL)引起的炎症损伤的不同机制,阐述EL处理后减轻毒性的机制。结果显示,15种潜在的生物标志物,主要属于二萜,进行筛选以区分EL和PEL。EL促进TLR4、NLRP3、NF-κBp65、IL-1β和TNF-α的表达,增加脂筏丰度并促进TLR4定位到脂筏。同时,EL降低LXRα和ABCA1表达,和减少胆固醇流出。与EL相比,PEL对这些指标的影响明显减弱。此外,大黄因子L1、L2和L3影响LXRα,ABCA1、TLR4、NLRP3、NF-κBp65、TNF-α和IL-1β表达,影响胆固醇流出和脂筏丰度,并干扰TLR4和脂筏的共定位。加工EL引起的炎症损伤明显弱于粗EL,一品红因子L1,L2和L3的减少以及炎症损伤的减轻参与了EL的基于加工的解毒。我们的研究结果为EL炮制的衰减机理提供了有价值的见解,并将指导未来有毒中药炮制机理的研究。
Euphorbia lathyris L. (EL) is a traditional poisonous herbal medicine used to treat dropsy, ascites, amenorrhea, anuria and constipation. Processing to reduce toxicity of EL is essential for its safe and effective application. However, there is little known regarding the molecular mechanism of reducing toxicity after EL processing. This research aimed to screen the differential markers for EL and PEL, explore the differential mechanisms of inflammatory injury induced by EL and processed EL (PEL) to expound the mechanism of alleviating toxicity after EL processing. The results showed that 15 potential biomarkers, mainly belonging to diterpenoids, were screened to distinguish EL from PEL. EL promoted the expressions of TLR4, NLRP3, NF-κB p65, IL-1β and TNF-α, increased lipid rafts abundance and promoted TLR4 positioning to lipid rafts. Meanwhile, EL decreased LXRα and ABCA1 expression, and reduced cholesterol efflux. In contrast to EL, the effects of PEL on these indicators were markedly weakened. In addition,
Euphorbia factors L1, L2, and L3 affected LXRα, ABCA1, TLR4, NLRP3, NF-κB p65, TNF-α and IL-1β expression, influenced cholesterol efflux and lipid rafts abundance, and interfered with the colocalization of TLR4 and lipid rafts. The inflammatory injury caused by processed EL was significantly weaker than that caused by crude EL, and reduction of
Euphorbia factors L1, L2, and L3 as well as attenuation of inflammatory injury participated in processing-based detoxification of EL. Our results provide valuable insights into the attenuated mechanism of EL processing and will guide future research on the processing mechanism of toxic traditional Chinese medicine.