School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China.
Fitoterapia. 2024 Sep;177:106111. doi: 10.1016/j.fitote.2024.106111. Epub 2024 Jul 4.
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 L, L, and L 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 L, L, and L 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.
大狼毒（Euphorbia lathyris L.，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。降低大狼毒的毒性对于其安全有效应用至关重要。然而，对于大狼毒炮制后降低毒性的分子机制知之甚少。本研究旨在筛选大狼毒和炮炙大狼毒（processed Euphorbia lathyris，PEL）的差异标志物，探索 EL 和 PEL 诱导炎症损伤的差异机制，阐明 EL 炮制减毒的机制。结果表明，筛选出 15 个潜在的生物标志物，主要属于二萜类化合物，用于区分 EL 和 PEL。EL 促进 TLR4、NLRP3、NF-κB p65、IL-1β 和 TNF-α 的表达，增加脂筏的丰度，并促进 TLR4 向脂筏定位。同时，EL 降低了 LXRα 和 ABCA1 的表达，减少了胆固醇外排。与 EL 相比，PEL 对这些指标的影响明显减弱。此外，大狼毒因子 L、L 和 L 影响 LXRα、ABCA1、TLR4、NLRP3、NF-κB p65、TNF-α 和 IL-1β 的表达，影响胆固醇外排和脂筏丰度，并干扰 TLR4 和脂筏的共定位。炮制后的大狼毒引起的炎症损伤明显弱于生品大狼毒，大狼毒因子 L、L 和 L 的减少以及炎症损伤的减弱参与了 EL 的炮制解毒。我们的研究结果为 EL 炮制解毒的减弱机制提供了有价值的见解，并将指导未来对毒性中药炮制机制的研究。
