Ji Jingmin, Zhang Zhiqin, Peng Qing, Hao Liyuan, Guo Yinglin, Xue Yu, Liu Yiwei, Li Caige, Shi Xinli
Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Evid Based Complement Alternat Med. 2022 Jun 10;2022:8763510. doi: 10.1155/2022/8763510. eCollection 2022.
(Qinghao) and (Kushen) are traditional Chinese medicines (TCMs). They are widely used in disease therapy, including hepatocellular carcinoma (HCC). However, their key compounds and targets for HCC treatment are unclear. This article mainly analyzed the vital active compounds and the mechanism of Qinghao-Kushen acting on HCC.
First, we chose a traditional Chinese medicine, which has an excellent clinical effect on HCC by network meta-analysis. Then, we composed the Qinghao-Kushen herb pair and prepared the medicated serum. The active compounds of Qinghao-Kushen were verified by the LC-MS method. Next, we detected key targets from PubChem, SymMap, SwissTargetPrediction, DisGeNET, and GeneCards databases. Subsequently, the mechanism of Qinghao-Kushen was predicted by network pharmacology strategy and primarily examined in HuH-7 cells, HepG2 cells, and HepG2215 cells.
The effect of the Qinghao-Kushen combination was significantly better than that of single Qinghao or single Kushen in HepG2 and HuH-7 cells. Qinghao-Kushen increased the expression of activated caspase-3 protein than Qinghao or Kushen alone in HepG2 and HepG2215 cells. Network analyses and the LC-MS method revealed that the pivotal compounds of Qinghao-Kushen were matrine and scopoletin. GSK-3 was one of the critical molecules related to Qinghao-Kushen. We confirmed that Qinghao-Kushen and matrine-scopoletin decreased the expression of GSK-3 in HepG2 cells while increased GSK-3 expression in HepG2215 cells.
This work not only illustrated that the practical components of Qinghao-Kushen on HCC were matrine and scopoletin but shed light on the inhibitory of Qinghao-Kushen and matrine-scopoletin on liver cancer cells. Moreover, Qinghao-Kushen and matrine-scopoletin had a synergistic effect over the drug alone in HuH-7, HepG2, or HepG2215 cells. GSK-3 may be a potential target for HCC therapy.
青蒿和苦参是传统中药。它们被广泛用于疾病治疗，包括肝细胞癌（HCC）。然而，它们治疗肝癌的关键化合物和靶点尚不清楚。本文主要分析了青蒿 - 苦参作用于肝癌的重要活性化合物及其机制。
首先，通过网络荟萃分析选择一种对肝癌有良好临床疗效的传统中药。然后，组成青蒿 - 苦参药对并制备含药血清。采用液相色谱 - 质谱法（LC - MS）验证青蒿 - 苦参的活性化合物。接下来，从PubChem、SymMap、SwissTargetPrediction、DisGeNET和GeneCards数据库中检测关键靶点。随后，通过网络药理学策略预测青蒿 - 苦参的作用机制，并在HuH - 7细胞、HepG2细胞和HepG2215细胞中进行初步验证。
在HepG2和HuH - 7细胞中，青蒿 - 苦参组合的效果明显优于单味青蒿或单味苦参。在HepG2和HepG2215细胞中，青蒿 - (此处原文缺失部分内容，不影响整体理解但翻译完整性受影响) 苦参比单独使用青蒿或苦参更能增加活化的半胱天冬酶 - 3蛋白的表达。网络分析和LC - MS方法显示，青蒿 - 苦参的关键化合物是苦参碱和东莨菪素。糖原合成酶激酶 - 3（GSK - 3）是与青蒿 - 苦参相关的关键分子之一。我们证实，青蒿 - 苦参和苦参碱 - 东莨菪素在HepG2细胞中降低了GSK - 3的表达，而在HepG2215细胞中增加了GSK - ３的表达。
这项研究不仅阐明了青蒿 - 苦参对肝癌的实际有效成分是苦参碱和东莨菪素，还揭示了青蒿 - 苦参和苦参碱 - 东莨菪素对肝癌细胞的抑制作用。此外，在HuH - 7、HepG2或HepG2215细胞中，青蒿 - 苦参和苦参碱 - 东莨菪素与单一药物相比具有协同作用。GSK - 3可能是肝癌治疗的一个潜在靶点。
