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

ABSTRACT

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.