OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction (SBJDD), a traditional Chinese medicine (TCM) prescription clinically used for the treatment of colorectal adenoma (CRA), and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.
METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry (UPLC-Q-TOF-MS) method was established to detect the chemical components in the decoction of SBJDD and the plasma samples of rats after administration with SBJDD.Based on the network pharmacological method, SBJDD was screened for the potential active ingredients at different stages of CRA carcinogenesis, and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer (CRC) action of SBJDD.
RESULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage, the potential active ingredients in SBJDD, including epiberberine, and kushenol H, might affect target proteins such as PIK3CA, MAPK3 and PIK3CB.This, in turn, can influence signaling pathways like PI3K-AKT and Ras signaling pathways, and regulate biological processes like protein phosphorylation, and signal transduction.During the CRA stage, the potential active ingredients from SBJDD, such as 3, 7-dihydroxycoumarin, palmatine, and kushenol A, might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process, and positive regulation of cell proliferation, and modify HIF-1, and Rap1 signaling pathways.During the progression of CRA carcinogenesis, potential active ingredients such as 3, 7-dihydroxycoumarin may interact with TP53, and impact the PI3K-AKT, and Thyroid hormone signaling pathways to regulate biological processes, including positive regulation of transcription from RNA polymerase Ⅱ promoter, and negative regulation of apoptotic process.In the CRC stage, core ingredients like p-coumaric acid may bind with proteins such as PRKCB.This binding may impact the signaling pathways that negatively affect EGFR tyrosine kinase inhibitor resistance, and PI3K-AKT signaling pathways.Additionally, it may regulate biological processes, including negative regulation of apoptotic process, signal transduction, and protein phosphorylation.In vitro experiment results indicated that SBJDD inhibited the proliferation of HT29 cells and suppressed the expression of EGFR and PKC proteins.
CONCLUSION The UPLC-Q-TOF-MS method is established to effectively separate the chemical constituents in SBJDD, which are mainly composed of alkaloids, organic acids and flavonoids components.Components from SBJDD dock with different targets during the carcinogenesis process of CRA and regulate cancer-related signaling pathways to exert therapeutic effects.
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