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The root of Tripterygium wilfordii has the effect in dispelling wind and eliminating dampness. Now it is mostly used in the treatment of systemic lupus erythematosus and other diseases. Triptonide is a diterpene small molecule compound extracted from T. wilfordii. In the early years， it was studied as a potential drug with anti-inflammatory and anti-reproductive effects. Recently， researchers found that its anti-tumor effect was particularly prominent because triptonide could inhibit the growth of a variety of tumors with different mechanisms at the nanomole dose， with a potential to be used as a broad-spectrum anti-cancer drug. In addition， due to the low yield from T. wilfordii， low bioavailability due to poor water solubility and anti-reproductive side effect as an antitumor drug， it will become study hotspots to exploring its synthesis and preparation and modifying its structure to reduce cost， improve bioavailability and reduce side effect， while maintaining its pharmacological activity. The authors reviewed domestic and foreign studies and patents on triptonide， and summarized its pharmacological activity and mechanism. It is found that although current studies on triptonide are still in the preliminary stage， there have been increasingly more studies on its anti-tumor mechanism year by year since 2014. This paper mainly introduces the antitumor pharmacological activity and mechanism of triptonide. In addition， it reviews anti-inflammatory， immunosuppression and anti-reproductive pharmacological effect of triptonide， as well as the existing studies on its toxicity， synthesis and structural modification. The authors put forward some personal ideas on its future study direction， in the hope to provide thinking and inspirations for other researchers and provide references for further development and research.
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Objective:This study aims to investigate the effect of triptonide （TN） on proliferation， cell cycle， apoptosis and expressions of apoptosis-related proteins of human acute monocytic leukemia（AML） cell line SHI-1， and to explore its possible mechanism of action. Method:The thiazolyl blue （MTT） colorimetric assay was applied to detect the inhibitory effect of 20，40，80，160，320 nmol·L<sup>-1</sup> triptonide on the proliferation of SHI-1 cells for 48， 72 h. Changes in SHI-1 cell cycle before and after triptonide treatment were detected by flow cytometry propidium iodide （PI） simple staining， and changes in SHI-1 cell apoptosis before and after triptonide treatment were detected by flow cytometry with AnnexinV/PI double staining. Western blot was applied to detect the protein expression of cysteine protease （Caspase）-3， Caspase-8 and nuclear transcription factor kappaB（NF-<italic>κ</italic>B） in SHI-1 cells before and after treatment with 80， 160 nmol·L<sup>-1 </sup>triptonide. Result:Compared with the blank group， 40，80，160，320 nmol·L<sup>-1</sup> triptonide significantly inhibited the proliferation of SHI-1 cells（<italic>P</italic><0.01） in a dose-dependent manner for 48， 72 h， while 160， 320 nmol·L<sup>-1 </sup> triptonide induced apoptosis of SHI-1 cells（<italic>P</italic><0.01） for 48， 72 h， and 160 nmol·L<sup>-1</sup> triptonide could decrease the S phase ratio of SHI-1 cells（<italic>P</italic><0.01）. In addition， compared with the blank group， 80，160 nmol·L<sup>-1</sup> triptonide induced the downregulation of NF-<italic>κ</italic>B significantly（<italic>P</italic><0.01）， 160 nmol·L<sup>-1</sup> triptonide induced the downregulation of Caspase-3， Caspase-8 significantly（<italic>P</italic><0.01）. Conclusion:Triptonide can inhibit the proliferation and induce apoptosis <italic>in vitro</italic> of SHI-1 cells， which may be related to the reduction of the cells in S phase proportion by triptonide， and the downregulation of the expression levels of Caspase-3， Caspase-8 and NF-<italic>κ</italic>B proteins.
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Objective::To observe the effect of realgar nanoparticles (a representative drug in toxin eliminating therapeutics) targeting hypoxia-inducible factors (HIF), which act as effector molecules on metabolic reprogramming of lung cancer stem cells, and to explore the effect mechanism of lung cancer stem cells and metabolic reprogramming in the process of lung cancer metastasis, so as to verify the effectiveness of toxin eliminating therapeutics in the prevention and treatment of lung cancer metastasis. Method::Lung cancer A549 cells were cultured in vitro, and lung cancer stem cells were then identified and selected. The stem cells were divided into blank control group, cisplatin group (5 mg·L-1), realgar nanoparticles low, medium and high dose groups (100, 200, 400 mg·L-1). After intervention, glucose oxidase method was used to detect the effect of realgar nanoparticles on the glucose metabolism of lung cancer stem cells, real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of hypoxia-inducible factors-1α (HIF-1α), C-myc and p53, while Western blot was used to detect the expression of related proteins HIF-1α, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and enzyme linked immunosorbent assay (ELISA) was used to detect the glucose transporter 1 (GLUT1), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M (PKM), phosphofructokinase(PFK), pyruvate dehydrogenase (PDH) and lactic dehydrogenase (LDH) expression. Result::As compared with the blank control group, realgar nanoparticles can reduce the glucose consumption of lung cancer stem cells, and the glucose consumption was reduced with the increase of dose in a time-and dose-dependent manner (P<0.01). Realgar nanoparticles can inhibit the mRNA expression of HIF-1α, a key factor in metabolic reprogramming of lung cancer stem cells (P<0.05, P<0.01), down-regulated C-myc mRNA and up-regulated the p53 mRNA expression (P<0.05, P<0.01), down-regulated protein expressions of PI3K, Akt, mTOR(P<0.05, P<0.01), and inhibited the expression of related enzymes GLUT1, PDK1, PFK, PKM, PDH, and LDH levels (P<0.05, P<0.01). With the increase of dose, the regulation and control ability of realgar nanoparticles gradually increased. Conclusion::Toxin eliminating therapeutics can drive the metabolic reprogramming of lung cancer stem cells by targeting HIF effector molecule, and then inhibit the invasion and metastasis of lung cancer.
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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.
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Realgar is toxic and belongs to drug of poison attack, with anti-cancer, anti-pest, dry wet and expectorant effects. Ancient doctors often used realgar to treat carbuncle, boil, abdominal pain and other diseases. Modern doctors use it to treat malignant tumors and blood diseases. The toxicity of realgar results in a small range of safety in its drug use. Modern scholars combine traditional Chinese medicine with nano-technology means to grind realgar into nano-realgar. Compared with realgar, nano-realgar has an improved bioavailability and reduced toxicity in vivo. Modern pharmacological researches use nano-realgar to interven lung cancer cells, skin cancer cells, cervical cancer cells, ovarian cancer cells and leukemia cells in experiments, which confirmed that nano-realgar has effects in inhibiting cell proliferation, inducing apoptosis and cell differentiation, inhibiting nucleic acid synthesis and angiogenesis, but with antiviral, sterilization of analgesic effects. Modern toxicological studies have been conducted in mice through intragastric treatment with different concentrations of nano-realgar preparation. The symptoms and signs of mice and various auxiliary examination indexes were recorded at different time periods. It was concluded that nano-realgar has regular effects on blood biochemical indexes at safe doses. In clinical trials, nano-realgar was applied to treat damaged wound surface of malignant tumor. It was found that nano-realgar can promote healing of wound surface of tumor, alleviate pain, relieve clinical symptoms, such as bleeding, purulence and odor, and improve quality of life of patients. In addition, with a simple usage and good patient compliance, administration with nano-realgar requires no hospitalization, can save medical resources, and is worthy of clinical promotion and application.
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<p><b>OBJECTIVE</b>To study the effect and mechanism of soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (sDC-SIGN) on the phagocytosis of Staphylococcus aureus (S. aureus) by immature dendritic cells (imDCs).</p><p><b>METHODS</b>Flow cytometry was employed to examine the effect of sDC-SIGN on the phagocytosis of S. aureus by imDCs. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the binging of sDC-SIGN to S. aureus, lipoteichoic acid (LTA) and lipopolysaccharides (LPS) and investigate the effect of the ligands mannan and LTA and anti-DC-SIGN antibodies 1C6 and 4H3 on the binging of sDC-SIGN to S. aureus.</p><p><b>RESULTS</b>sDC-SIGN inhibited the phagocytosis of S. aureus by imDCs. sDC-SIGN bound to S. aureus in a Ca(2+)-dependent manner. sDC-SIGN concentration-dependently bound to LTA, but not to LTA, and the binging of sDC-SIGN to S. aureus was blocked by mannan, LTA, 1C6 and 4H3.</p><p><b>CONCLUSION</b>sDC-SIGN preferentially binds to the carbohydrate constituents on S. aureus to affect the binding between membrane-bound DC-SIGN and S. aureus, thus suppressing the phagocytosis of S. aureus by imDCs.</p>
Subject(s)
Humans , Cell Adhesion Molecules , Metabolism , Dendritic Cells , Cell Biology , Metabolism , Lectins, C-Type , Metabolism , Lipopolysaccharides , Phagocytosis , Receptors, Cell Surface , Metabolism , Staphylococcus aureus , Teichoic AcidsABSTRACT
Objective To explore the effect of open storage and peeling on the fluorine content of dried com in order to provide a scientific basis for prevention and treatment of coal-combustion fluorosis. Methods In October 2006, 34 samples of freshly dried and 3-month old dried com were sampled in Zhenxiong county, Zhaotong city, Yunnan province. Fluorine content in corn was determined by combustion-hydrolysis-ion selective electrode method. Results The average fluorine content of freshly dried corn by coal-combustion was (4.29 ±1.87)mg/kg,and increased to (6.64±2.64)mg/kg after they had been openly stored for three months and the average content increased by 54.74%. But if corn was peeled off, their fluorine content decreased to (5.03±2.04)mg/kg at a rate of 24.25%. The amount of fluorine absorbed by the skin of corn was more than other parts of com during corn desiccation. Conclusions The inhabitants in coal-combustion fluorosis areas ingest less fluorine through dry com if they eat the peeled corn and take measures to keep it airtight and moisture-proof during storage thus reducing the harm of coal-combustion fluorosis.
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Objective To assess the fluorine (F), arsenic (As) and selenium (Se) levels in hair of residents from the fluorosis area of Zhaotong and provide reference basis for the evaluation of the health status of populations in fluorosis areas as well as the prevention and control of fluorosis in Zhaotong. Methods Sixty-five hair samples were collected in fluorosis areas(Zhenxiong, Weixin County), including. 41 samples from 6 endemic townships and 24 samples from a non-endemic township. Fluorine content in hair was determined by combustion- hydrolysis-ion selective electrode method. Arsenic and selenium contents in hair were determined by atom- fluorescence method. Results The average contents of hair fluorine, arsenic and selenium contents were (15.1807±15.2397), (2.1806±1.9601), (2.3162±2.4535)mg/kg in the 41 patients with fluorosis and were (18.7703±17.1067), 0.3283±0.2466), (1.2805±0.6970) mg/kg in the 24 inhabitants (control). The difference of fluorine content in hair between patients in fluorosis and control inhabitants was not statistically significant (P 0.05), but the difference in arsenic and selenium content was statistically significant (P<0.05). Conclusions Mild arsenic pollution exists in Zhaotong fluorosis areas, which aggravates the prevalence of fluorosis. Food roasted with blended coal contains high fluorine. Meanwhile it may bring in the supplement of selenium for the inhabitants in Zhaotong fluorosis areas.