RESUMEN
BACKGROUND: Yujin powder (YJP) is a classic prescription for treating dampness-heat diarrhea (DHD) in Traditional Chinese Medicine (TCM), but the main functional active ingredients and the exact mechanisms have not been systematically studied. OBJECTIVES: This study aimed to preliminarily explore the potential mechanisms of YJP for treating DHD by integrating UPLC-MS/MS and network pharmacology methods. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the ingredients of YJP. And then, the targets of these components were predicted and screened from TCMSP, SwissTargetPrediction databases. The disease targets related to DHD were obtained by using the databases of GeneCards, OMIM, DisGeNET, TTD, and DrugBank. The protein-protein interaction networks (PPI) of YJP-DHD were constructed using the STRING database and Origin 2022 software to identify the cross-targets by screening the core-acting targets and a network diagram by Cytoscape 3.8.2 software was also constructed. Metascape database was used for performing GO and KEGG enrichment anlysis on the core genes. Finally, molecular docking was used to verify the results with AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL 2.4.0, and Open Babel 2.3.2 software. RESULTS: 597 components in YJP were detected, and 153 active components were obtained through database screening, among them the key active ingredients include coptisine, berberine, baicalein, etc. There were 362 targets treating DHD, among them the core targets included TNF, IL-6, ALB, etc. The enriched KEGG pathways mainly involve PI3K-Akt, TNF, MAPK, etc. Molecular docking results showed that coptisine, berberine, baicalein, etc., had a strong affinity with TNF, IL-6, and MAPK14. Therefore, TNF, IL-6, MAPK14, ALB, etc., are the key targets of the active ingredients of YJP coptisine, baicalein, and berberine, etc. They have the potential to regulate PI3K-Akt, MAPK, and TNF signalling pathways. The component-target-disease network diagram revealed that YJP treated DHD through the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury. CONCLUSION: It is demonstrated that YJP treats DHD mainly through the main active ingredients coptisine, berberine, baicalein, etc. comprehensively exerting the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury, which will provide evidence for further in-depth studying the mechanism of YJP treating DHD.
RESUMEN
AIM: Our previous works have demonstrated that Chinese herb medicine yanhusuo (Corydalis yanhusuo W. T. Wang) has strong anti-cancer proliferation effect in MDA-MB-231 cells. The goal of this study was to find out the synergic cytotoxicity effect of three natural compounds, tetrahydropalmatine (THP), berberine (Ber), and dehydrocorydaline (DHC), isolated from C. yanhusuo W. T. Wang. MATERIALS AND METHODS: The IC50 of THP Ber and DHC in single use, as well as in combination use at fixed ratios and doses was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Isobologram, combination index and modified coefficient of drug interaction (CDI) methods were used for evaluation the combination effects of THF! Ber, and DHC in different ratio and concentration. RESULTS: The results indicated that the combination of THP and Ber shown the strongest anti-cancer cell proliferation effect at the ratio of 2:3 (Ber: THF the average CDI value was 0.5795). DHC and THP have additive cytotoxicity in MDA-MB-231 cells. However, there wasn't any synergistic effect between Ber and DHC, and it even exhibited antagonistic effect when the percentage of DHC was >50%. CONCLUSION: Our findings suggested that the combination of THP and Ber might be beneficial for anti-proliferation of MDA-MB-231 breast cancer cells through a significant synergy effect.
