Synthesis and Biological Evaluation of Steviol Derivatives with Improved Cytotoxic Activity and Selectivity.

Steviol is an ent-kaurene diterpenoid with interesting pharmacological activity. Several steviol derivatives with an exo-methylene cyclopentanone unit were discovered as potent antitumor agents. However, their poor selectivity for tumor cells relative to normal cells reduces their prospects as potential anticancer drugs. In this study, based on previous work, 32 steviol derivatives, including 28 new analogues, were synthesized. Their cytotoxicity against tumor cells and normal cells was evaluated. Several new derivatives, such as 7a, 7h, and 8f, with improved cytotoxic selectivity and antiproliferative activity were obtained, and the structure-activity relationship correlations were investigated. The new compound 8f displayed potent antiproliferative activity against Huh7 cells (IC50 = 2.6 µM) and very weak cytotoxicity against the corresponding normal cells HHL5 (IC50 = 97.0 µM). Further investigation showed that 8f arrested the cell cycle at the G0/G1 phase and caused reactive oxygen species overproduction, decreased mitochondrial membrane potential, and induced apoptosis of Huh7 cells through inhibition of the PI3K/Akt/mTOR and NF-κB pathway as well as upregulation of Bax/Bcl-2 ratio. The present study suggested that 8f is a promising lead compound for new cancer therapies, and the results presented herein may encourage the further modification of steviol for additional derivatives with enhanced efficacy and selectivity.

[Nondestructive recognization of mountain cultivated ginseng and garden cultivated ginseng by FTIR microspectroscopy].

Fourier transform infrared (FTIR) microspectroscopy technology is the combination of the FTIR spectrometer and the microscope. This technology is of simple preparation of the samples, can be used in micro-area analysis and micro-samples, and reflect the nature of the samples spectra. Panax ginseng include mountain cultivated ginseng (MCG), garden cultivated ginseng (GCG) and mountain wild ginseng (MWG), but the excavation of MWG is prohibited in China. So, only MCG and GCG were collected and recorded in Chinese pharmacopoeia. In this study, we developed a discriminant analysis (DA) method for recognition of MCG and GCG using FTIR microspectroscopy technology. Twenty MCG samples and twenty four GCG samples were obtained, and their spectra of IR microspectroscopy were collected. Then 33 samples were randomly selected into calibration set and the remaining 11 of the samples were selected into validation set. The authors optimized the pretreatment method, the principal components, the modeling region and the scanning parts when developing the models. The optimized model of discriminant analysis was developed using the pretreatment multiplicative scatter correction (MSC) + Savitzky-Golay filter (SG) smoothing, the region 3 932.14-669.18 cm(-1), 4 principal components and the rhizome part. The accuracy of the optimized model got up to 100%. The result demonstrated that infrared microspectroscopy technology combined with DA is of simple operation, rapid, nondestructive and effective, and can be applied to recognize MCG and GCG.

Efficacy and safety of intravenous stronger neo-minophagen C and S-adenosyl-L-methionine in treatment of pregnant woman with chronic hepatitis B: a pilot study.

BACKGROUND: There have been no studies evaluating the efficacy and potential risks of stronger neo-minophagen C (SNMC) in pregnant women with chronic hepatitis B CHB. MATERIAL/METHODS: A total of 36 pregnant women with CHB, but without severe complications, were randomized to intravenously receive SNMC or S-adenosyl-L-methionine (SAM) daily for 4 weeks or until birth. Normalization of serum alanine transaminase (ALT) and aspartate transaminase (AST) levels and changes in ALT and AST levels from baseline were determined. All neonates were regularly examined for up to 1 year. RESULTS: Treatment with SNMC and SAM resulted in normalization of ALT levels at 4 weeks in 64.3% and 21.4% of patients, respectively (OR=6.60, 95% CI: 1.23-35.44, P=0.0540). SNMC and SAM significantly decreased ALT (from 558.28+/-390.24 to 47.07+/-24.94 IU/L, P<0.0001 and from 525.61+/-483.87 to 117.43+/-85.44 IU/L, P=0.0041, respectively) and AST (from 419.72+/-409.49 to 38.14+/-18.87 IU/L, P=0.0016, and from 510.78+/-621.58 to 79.93+/-63.25 IU/L, P=0.0152, respectively) at 4 weeks relative to baseline values. Hypokalemia was observed in 4 SNMC-treated patients and in 2 SAM-treated patients and hypernatremia in 3 SNMC-treated and in 3 SAM-treated patients. Hypertension was observed in 1 SNMC-treated patient. There was no significant difference in the volume of amniotic fluid or meconium between SNMC-treated and SAM-treated groups. All the neonates were physically normal at birth and at the 1-year follow-up examination. CONCLUSIONS: Both SNMC and SAM improve liver function, with SNMC appearing more effective, in pregnant women with chronic hepatitis B without impact on fetal development.