Ethnopharmacological relevance: Colorectal cancer is a common digestive tract malignant tumor that its morbidity and mortality seriously affect human health. At present, Da Cheng Qi Tang, a traditional Chinese medicine formula, has been clinically used as an adjuvant therapy for colorectal cancer. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear.
Aim of the study: The main constituents absorbed in the blood and possible active targets after Da Cheng Qi Tang administration were explored based on the analysis method of “into serum components, action target and key pathway”, which may provide reference for the study of the pharmacodynamic material basis and action mechanism of Dachengqi Decoction in the treatment of colorectal cancer.
Material and methods: Based on the serum pharmacochemistry of traditional Chinese medicine (TCM), the prescription prototype ingredients of Da Cheng Qi Tang in mice serum samples were identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology (UPLC-Q-TOF-MSE). Taking the prototype ingredients absorbed into serum as the research object, the possible targets and key pathways of Da Cheng Qi Tang in vivo were demonstrated by network pharmacology. Finally, using molecular docking verified the binding activity of prototype components and potential action targets.
Results: A total of 46 prototype components of Da Cheng Qi Tang were identified in mice serum, most of which were derived from flavonoids and anthraquinones in Citrus aurantium L. and Rheum palmatum L. Network pharmacology prediction results indicated that the drug prototype components entering the serum may mainly regulate targets including mitogen-activated protein kinase (MAPK), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. and main pathways such as (phosphatidylinositol 3-kinase/protein kinase B) PI3K-AKT signaling pathway, advanced glycation end products-receptor for AGE (AGE-RAGE) signaling pathway and IL-17 signaling pathway, etc. Molecular docking showed that the prototype active components had strong binding activity to VEGF, Harvey rat sarcoma viral oncogene homolog (HRAS) and MAPK1.
Conclusions: This study elucidated that most of the direct acting substances of Da Cheng Qi Tang in vivo were flavonoids and anthraquinones, which may play a role in regulating cell reproduction and apoptosis and inhibiting inflammation, providing a reference for the research of pharmacodynamic material basis and mechanism of Da Cheng Qi Tang in the treatment of colorectal cancer.