Synthesis and Antitumor Activity of Panaxadiol Pyrazole and Isooxazole Derivatives.

In this study, we designed and synthesized 19 nitrogen-containing heterocyclic derivatives of panaxadiol (PD). We first reported the antiproliferative activity of these compounds against four different tumor cells. The results of the MTT assay showed that the PD pyrazole derivative (compound 12b) had the best antitumor activity and could significantly inhibit the proliferation of four tested tumor cells. For A549 cells, the IC50 value was as low as 13.44±1.23 µM. Western blot analysis showed that the PD pyrazole derivative was a bifunctional regulator. On the one hand, it can down-regulate the expression of HIF-1α by acting on PI3 K/AKT signaling pathway in A549 cells. On the other hand, it can induce the decrease of CDKs protein family and E2F1 protein expression levels, thus playing a crucial role in cell cycle arrest. According to the results of molecular docking, we found that multiple hydrogen bonds were formed between the PD pyrazole derivative and two related proteins, and the docking score of the derivative was also significantly higher than that of the crude drug. In summary, the study of the PD pyrazole derivative laid a foundation for the development of ginsenoside as an antitumor agent.

Steroidal saponins and sapogenins from fenugreek and their inhibitory activity against α-glucosidase.

The seed of Trigonella foenum-graecum L. (fenugreek) has been reported to be rich in saponins, especially the dioscin or diosgenin, which are natural anti-diabetic agents with relatively low toxicity. Thus, the present study was to purify the saponins and sapogenins from fenugreek and to evaluate their α-glucosidase inhibitory activity in vitro. As a result, 33 steroidal saponins and sapogenins were isolated, including six undescribed ones and 27 previously known molecules. Among them, compounds 10, 12, 17, 22 and 29 were five 25R and 25S isomer mixtures of spirostanol saponins or sapogenins. The structures of compound 1-6 were established by 1D and 2D NMR spectroscopic analyses, high-resolution mass spectrometry, and chemical evidence. Compared to the positive control, sapogenins 26, 27, 14 and saponins 18 and 23 considerably inhibited α-glucosidase at IC50 values of 15.16, 8.98, 7.26, 5.49 and 14.01 µM, respectively. These results support the therapeutic potential of fenugreek in the treatment of diabetes with saponins and sapogenins as the active constituents.

Optimization of flash extraction, separation of ginsenosides, identification by HPLC-FT-ICR-MS and determination of rare ginsenosides in mountain cultivated ginseng.

In this paper, we used the flash extraction method (FEM) to extract ginsenosides from mountain cultivated ginseng (MCG), optimized the FEM process by response surface methodology (RSM), and separated 23 kinds of ginsenosides from MCG, including rare ginsenoside Rg3, 20(R/S)-Rg2, Rk3, 20(S)-Rh2, 20(R)-Rh1, F1 and Rg6. Among them, notoginsenoside R1 was isolated from MCG for the first time. Additionally, we established an HPLC-FT-ICR-MS method to accurately identify 20 ginsenosides in MCG, and quantitatively analyzed the differences in the content of rare ginsenosides in MCG and Garden-Cultivated Ginseng (CG) by HPLC-UV. The results showed that the chemical components of MCG and CG were similar, but the ginsenoside content of MCG was double that of CG. Notably, the content of ginsenoside 20 (S)-Rh2 and 20 (R)-Rh1 had the largest difference, and the content in MCG was 33 and 24 times higher than that in CG, respectively. Through quantitative analysis, we clarified the reason why the activity of MCG is stronger than that of CG, which provided a theoretical basis for clinical application and further research of MCG.