Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction / 中国天然药物

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α

Identification of neprilysin as a potential target of arteannuin using computational drug repositioning

ABSTRACT The discovery of arteannuin (qinghaosu) in the 20th Century was a major advance for medicine. Besides functioning as a malaria therapy, arteannuin is a pharmacological agent in a range of other diseases, but its mechanism of action remains obscure. In this study, the reverse docking server PharmMapper was used to identify potential targets of arteannuin. The results were checked using the chemical-protein interactome servers DRAR-CPI and DDI-CPI, and verified by AutoDock Vina. The results showed that neprilysin (also known as CD10), a common acute lymphoblastic leukaemia antigen, was the top disease-related target of arteannuin. The chemical-protein interactome and docking results agreed with those of PharmMapper, further implicating neprilysin as a potential target. Although experimental verification is required, this study provides guidance for future pharmacological investigations into novel clinical applications for arteannuin.

Screening of constituents with antiproliferative activity in Panax notoginseng and their underlying mechanisms / 中草药

Objective: To screen the components with potent antiproliferative effects on human hypertrophic scar fibroblasts (HSF) in Panax notoginseng and to explore their mechanisms. Methods: The Soxhlet extraction method was used to obtain the different extracts from P. notoginseng by solvents with different polarities. MTS method was used to screen the ingredients with antiproliferative activity on HSF and flow cytometry was used to detect their influence on cell cycle. Then, spectrum-activity relationship of the active ingredients was analyzed by HPLC. UPLC-Q/TOF-MS was used to identify the ingredients with obvious activity. The antiproliferative mechanism was predicted by reverse docking. Results: The ethyl acetate extract of P. notoginseng showed higher antiproliferative activity (P < 0.01), significantly increased the proportion of cells in G0/G1 phase (P < 0.01), and reduced the proliferation index (PI) (P < 0.01). The main active components were saponins. The result of confirming experiment showed that ginsenosides Rh1 and Rg1 could inhibit the cell proliferation in a dose-dependent manner. Results of reverse docking indicated the antiproliferative effects might be related to the regulation of some target proteins such as MAP2K, MAPK14, and HRAS, as well as the related pathways. Conclusion: The ethyl acetate extract of P. notoginseng shows the antiproliferative activity on HSF, and the antiproliferative ingredients are saponins. The underlying mechanisms might be related with the regulation of MAPK and focal adhesion signaling pathways.