ABSTRACT
Objective:To investigate the effects of arsenic trioxide combined with dihydroartemisinin on proliferation, cell cycle, and apoptosis of THP-1 cells, and explore the mechanism. Method:The thiazolyl blue （MTT） method was applied to detect the effect of different concentrations of arsenic trioxide, dihydroartemisinin and arsenic trioxide combined with dihydroartemisinin on the proliferation of THP-1 cells. Annexin V/propidium iodide（PI）assay was used to detect the change of THP-1 cell cycle and apoptosis．Western blot was performed to assess the expression of cysteine protease-3（Caspase-3）, cleaved Caspase-3, B-lymphocytoma-2（Bcl-2） and Bcl-2 associated X protein （Bax）. The changes of cell morphology were observed under high intension microscope. Result:Compared with blank group, arsenic trioxide and dihydroartemisinin both exhibited obvious antiproliferative effect on the human acute monocytic leukemia cell line THP-1 in time-dose dependence （P<0.01）. After 48 h, compared with the same dose of arsenic trioxide or that of dihydroartemisinin alone, the inhibition effect of 1 µmol·L-1 arsenic trioxide combined with 2 µmol·L-1 dihydroartemisinin on proliferation of THP-1 cells was significantly stronger （P<0.01）. Compared with the control group, arsenic trioxide combined with dihydroartemisinin significantly arrested the cells in G1 phase （P<0.01）, induced the downregulation of Caspase-3 and Bcl-2 （P<0.01） and upregulation of cleaved Caspase-3 significantly（P<0.05）. Conclusion:Arsenic trioxide combined with dihydroartemisinin can significantly inhibit the proliferation and induce apoptosis of THP-1 cells. The possible mechanism may be related to arrest the cells in G1 phase, reduce the expression of Caspase-3 and Bcl-2, increase the expression of cleaved Caspase-3.
ABSTRACT
Imperatorin, which is extracted from umbelliferous plants such as Radix Angelicae Dahuricae, Radix Saposhnikoviae and Fructus Cnidii, belongs to furanocoumarins and is especially rich in Radix Angelicae Dahuricae. Research has shown that imperatorin possesses functions of anti-inflammatory, analgesic, antibactrial, antiviral, antiallergic, anti-tumor, reverse drug resistance in tumor cells, interaction with drug metabolizing enzymes, affecting cardiovascular and nervous system effect. It is also one of the standard components in quality control of various analgesics. In recent years, research findings related to imperatorin is increasing fast. A number of patent applications have been approved for the application of imperatorin in the treatment of anti-tumor and cardiovascular diseases. In addition, since the water insolubility of imperatorin affects its bioavailability, most researchers have gradually attached importance to this aspect of research, such as modifying its structure or synthesizing its derivatives. The literatures on the pharmacological effects and mechanisms of imperatorin at home and abroad in recent years were consulted and summarized in this paper. Imperatorin was found not only to display other pharmacological effects like furanocoumarins but also could cure osteoporosis, skin diseases and show photosensitization. Moreover, the mechanism of its action has the effect of multi-pathway and multi-target, but most of the studies have not identified its targets, which still needs further study. Extensive and significant pharmacological effect make imperatorin show a great potential for development of new drugs. This paper reviews the basic properties, the progress on pharmacological effects and mechanisms of imperatorin, proposes the research status and direction of future reseach. Hopes to provide ideas for researchers and beneficial references for the future development and utilization of imperatorin.
ABSTRACT
<p><b>AIM</b>To establish a new amino acid structure descriptor that can be applied to polypeptide QSAR studies.</p><p><b>METHODS</b>The new amino acid structure descriptor c-scales were derived from a principal components analysis of 167 amino acid structure descriptor indexes by theoretic calculation. The c1,c2,c3-scales were related to 3D structural features of amino acid such as steric, electronic and conformation properties etc. G/PLS regression method was used to find out the relationship between the c-scales and the biological activity and developed QSAR models of the polypeptides.</p><p><b>RESULTS</b>Using the established method, we developed accordingly QSAR models of Bitter tasting dipeptide, ACE inhibitors and bradykinin-potentiating pentapeptides and their r2 and XV-r2 were more than 0.70.</p><p><b>CONCLUSION</b>The c-scales can quantitatively describe the 3D structural features of any coded and non-coded amino acid and can be used to establish a QSAR model of good predictability.</p>