背景:根据中医(TCM),补充生命能量的药物,齐,可以通过恢复宿主免疫力来消除肿瘤。本研究的目的是探讨与益气中药相关的抗肿瘤活性的潜在免疫机制,特别是黄芪和当归的配对使用。
方法:进行配伍规律分析以筛选补气中药的组合。使用MTT法和移植瘤小鼠模型,在体外和体内研究了组合TCM的抗肿瘤作用。然后使用高含量分析和流式细胞术评估细胞免疫,其次是网络药理学和分子对接,以剖析重要的活性化合物和潜在的机制。最后,通过分子实验验证了活性成分的抗肿瘤活性和作用机制。
结果:黄芪和当归有一个最优组合,作为水提取物施用,可以激活免疫力来抑制肿瘤,并且在体外和体内比每种药物本身更有效。基于网络药理学分析,PIK3R1是黄芪和当归联合抗肿瘤免疫活性的核心靶点。分子对接分析表明当归和黄芪提取物的6个成分(槲皮素,jaranol,异鼠李素,山奈酚,calycosin,和suchilactone)与PIK3R1结合。Jaranol是对抗乳腺癌最重要的成分。Suchilactone/jaranol组合和,尤其是,舒拉内酯/山奈酚组合是增强免疫力和提取物抗肿瘤作用的关键。
结论:黄芪和当归合用可以激活免疫抑制乳腺癌,比单用单用药物更有效。
BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui.
METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.
RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.
CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.