Abstract：
Lamiophlomis Herba (LH) is a traditional Chinese and Tibetan dual-use herb with hemostatic and analgesic effects, and is widely used in the clinical treatment of traumatic bleeding and pain. In recent years, LH has been proven to treat liver fibrosis (LF), but the chemical components related to the pharmacological properties of LH in the treatment of LF are still unclear. Based on the theory of plasma pharmachemistry, the characteristic components in water extract and drug-containing plasma samples of LH were qualitatively analyzed by UPLC-Q-TOF-MS. The chemical components in plasma were screened and the targets were predicted by network pharmacology. Then, the predicted components and targets were verified in vitro by Elisa and qRT-PCR technology. Finally, the pharmacological effects of LH and its monomeric components were determined by hematoxylin-eosin staining of rat liver. A total of 50 chemical constituents were identified in LH, of which 12 were blood prototypes and 9 were metabolites. In vitro experiments showed that LH and its monomeric components luteolin, shanzhiside methyl ester, loganic acid, loganin, 8-O-acetyl shanzhiside methyl ester could increase the expression of antioxidant genes (NQO-1, HO-1) and decrease the expression of inflammatory genes (IL-6, IL-18), thereby reducing the expression of extracellular matrix-related genes and proteins (COL1A1, COL3A1, LN, α-sma, PC-III, Col-IV). In vivo experiments showed that LH could reduce the area of LF in rats in a dose-dependent manner, and shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester may be the main components in pharmacodynamics. These effects may be mediated by LH-mediated Nrf2/NF-κB pathway. This study explored the potential pharmacodynamic components of LH in the treatment of LF, and confirmed that shanzhiside methyl ester and 8-O-acetyl shanzhiside methyl ester play a key role in the treatment of LF with LH.
摘要：
LamiophlomisHerba（LH）是一种传统的中藏两用草药，具有止血和镇痛作用，并广泛应用于临床治疗创伤性出血和疼痛。近年来,LH已被证明可以治疗肝纤维化（LF），但与LH治疗LF的药理特性相关的化学成分仍不清楚。基于等离子体药理学理论，用UPLC-Q-TOF-MS定性分析了LH的水提取物和含药血浆样品中的特征成分。采用网络药理学方法对血浆中的化学成分进行筛选,并对靶点进行预测。然后，通过Elisa和qRT-PCR技术对预测的成分和靶标进行了体外验证。最后,通过大鼠肝脏的苏木精-伊红染色确定LH及其单体成分的药理作用。在LH中总共鉴定出50种化学成分，其中12是血液原型，9是代谢物。体外实验表明，LH及其单体成分木犀草素，山芝苷甲酯,loganicacid,loganin,8-O-乙酰山己苷甲酯可增加抗氧化基因(NQO-1,HO-1)的表达,降低炎症基因(IL-6,IL-18)的表达,从而降低细胞外基质相关基因和蛋白质的表达（COL1A1，COL3A1，LN，α-SMA,PC-III,Col-IV).体内实验表明，LH可以剂量依赖性地减少大鼠的LF面积，山芝苷甲酯和8-O-乙酰基山芝苷甲酯可能是药效学的主要成分。这些作用可能由LH介导的Nrf2/NF-κB途径介导。本研究探讨了LH治疗LF的潜在药效学成分，并证实山芝苷甲酯和8-O-乙酰基山芝苷甲酯在LH治疗LF中起关键作用。
