Multi-target drug design strategy and its research progress / 药学学报

Currently, single-target drugs are often difficult to achieve the desired results in the treatment of multifactorial diseases such as tumors, cardiovascular and endocrine diseases, and may also cause toxicity. Multi-target drugs can improve the efficacy, reduce side effect and drug resistance by regulating multiple links of the disease, showing good prospects for the application. The main aim of this article is to review the strategies of designing multi-target directed ligands (MTDLs) (including conjugated-pharmacophore, fused-pharmacophore and merged-pharmacophore) and the research progress in recent years. The existing problems and challenges of multi-target drugs are also discussed, to provide new ideas for the study of multi-target drugs.

Anticancer property of berberine in human colorectal adenocarcinoma / 中草药

Objective: To illustrate the anticancer property induced by berberine, which is extracted from Chinese medicine Coptidis Rhizoma. Methods: Human colorectal adenocarcinoma cells, HCT-15, were treated with different concentration of berberine. Cells were then observed under the optical microscope to analyze the morphological changes; CCK-8 assay was used to detect the inhibition of cell proliferation of HCT-15; Immunoblotting was used to detect the changes of autophagy and apoptosis related markers. Athymic mice injected with HCT-15 cells were used to detect the pharmacological activity of berberine in vivo. Results: After berberine treatment, with the increased dose of berberine, the cell number reduced, cell spacing increased, and cell shape shrunk. The IC50 for berberine treatment in HCT-15 cell was 50 μmol/L. Autophagy and apoptosis markers were enhanced after treatment of 0, 50, and 100 μmol/L of berberine. The data further showed that enhanced autophagy and apoptosis were the main contributors for inhibiting cell proliferation. Immunoblotting analysis showed that berberine induced HCT-15 cells to autophagy and apoptosis mainly through p38 pathway. Athymic mice study showed that berberine treatment could decrease the volume of tumor in vivo, and the tumor inhibitory rates by berberine at 0, 50, and 100 mg/kg were 0, 32% and 74%, respectively. Conclusion: Berberine inhibits the HCT-15 cell proliferation, mainly by p38 pathway and enhances autophagy and apoptosis. Berberine can effectively inhibit tumor growth in vivo.