Jiangsu Province Institute of Traditional Chinese Medicine

Nanjing, China

Jiangsu Province Institute of Traditional Chinese Medicine

Nanjing, China
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Jiangsu Province Institute Of Traditional Chinese Medicine | Date: 2017-02-14

A compound of Formula I or pharmaceutically acceptable salt thereof and its preparation method and applications, the new structure of the compound of formula I has not been reported in literature. It is isolated from Isodon forrestii var. forrestii and can be a compound served as Trx1 selective inhibitor. The present invention further discloses a pharmaceutical composition, preparation of the compound of Formula I and its applications in preparing medicines for preventing or treating cancer. Iso A of the present invention has the advantages of low toxicity, high safety and strong pharmacological effect, which suggests a potential prospect in pharmaceutical applications.

Wang M.,China Pharmaceutical University | Gao X.J.,University of Macau | Zhao W.W.,University of Macau | Zhao W.J.,China Pharmaceutical University | And 5 more authors.
British Journal of Pharmacology | Year: 2013

Background and Purpose Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. Experimental Approach To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. Key Results Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. Conclusion and Implications Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance. © 2013 The British Pharmacological Society.

Fan H.,Tongji University | Cao P.,Jiangsu Province Institute of Traditional Chinese Medicine | Game D.S.,King's College London | Dazzi F.,Imperial College London | And 3 more authors.
Seminars in Immunology | Year: 2011

The pursuit of transplantation tolerance is the holygrail in clinical organ transplantation. It has been established that regulatory T cells (Tregs) can confer donor-specific tolerance in mouse models of transplantation. However, this is crucially dependent on the strain combination, the organ transplanted and most importantly, the ratio of Tregs to alloreactive effector T cells. The ex vivo expansion of Tregs is one solution to increase the number of alloantigen specific cells capable of suppressing the alloresponse. Indeed, ex vivo expanded, alloantigen specific murine Tregs are shown to preferentially migrate to, and proliferate in, the graft and draining lymph node. In human transplantation it has been proposed that depletion of the majority of direct pathway alloreactive T cells will be required to tip the balance in favour of regulation. Ex vivo expansion of alloantigen specific, indirect pathway human Tregs, which can cross regulate the residual direct pathway has been established. Rapid expansion of these cells is possible, whilst they retain antigen specificity, suppressive properties and favourable homing markers. Furthermore, considerable progress has been made to define which immunosuppressive drugs favour the expansion and function of Tregs. Currently a series of clinical trials of adoptive Treg therapy in combination with depletion of alloreactive T cells and short term immunosuppression are underway for human transplantation with the aim of minimizing immunosuppressive drugs and completely withdrawal. © 2011 Elsevier Ltd.

To prevent protein aggregation, some proteins are usually expressed as fusion proteins from which target proteins can be released by proteolytic or chemical reagents. In this report, small ubiquitin-related modifier (SUMO) linked with a hexa-histidine tag was used as a fusion partner for the antitumor-analgesic peptide from the venom of Buthus martensii (Karsch) scorpion (AGAP). The optimal expression level of the soluble fusion protein, SUMO-AGAP, was up to 40% of the total cellular protein. The fusion protein was purified by Ni-NTA affinity chromatography and cleaved by a SUMO-specific protease (Ulp1) to obtain the recombinant AGAP (rAGAP), which was further purified by Ni-NTA affinity chromatography. The purified final product was >95% pure by SDS-PAGE stained with Coomassie brilliant blue R-250. Mass spectroscopic analysis indicated the protein to be 7142.63 Dalton, which equaled the theoretically expected mass. N-terminal sequencing of rAGAP showed the sequence corresponded to the native protein. MTT assay indicated the rAGAP could significantly inhibit the proliferation of Jurkat and Hut 78 T lymphoma cell lines. The further writhing experiment showed that the rAGAP had an intensive analgesic effect. The expression strategy presented in this study allows convenient high yield and easy purification of the rAGAP with native sequences. © 2010 American Institute of Chemical Engineers

Wu H.,Nanjing Medical University | Huang M.,Nanjing Medical University | Lu M.,Nanjing Medical University | Zhu W.,Nanjing Medical University | And 3 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013

Background: Human miR-34c has been reported to be associated with various human malignancies; however, it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer. The aim of this study was to investigate the role of miR-34c in gastric cancer. Materials and methods: The adenosine triphosphate-based tumor chemosensitivity assay was used to measure drug sensitivity in gastric cancer samples. The expression levels of miRNA were determined by reverse transcriptase polymerase chain reaction (PCR) and those of protein were by Western blot analysis. Luciferase activity assay was used to verify the target genes of miRNAs. MTT assay was used to test the drug-resistant phenotype changes in cancer cells via overregulation of miRNAs. The methylation status of neighboring CpG islands of miR-34c-5p was analyzed by Bisulfite Sequencing PCR and methylation-specific PCR. Results: Quantitative real-time polymerase chain reaction demonstrated that expression of miR-34c-5p was downregulated in paclitaxel-resistant gastric cancer samples (p < 0.01). Cells derived from gastric cancer tissues with low miR-34c-5p expression and high microtubule-associated protein tau (MAPT) protein expression tended to have increased chemoresistance to paclitaxel in vitro. Luciferase activity assay confirmed that the 3′-UTR of MAPT mRNA contains a functional miR-34c-5p binding site. Overexpression of miR-34c-5p significantly downregulated MAPT protein expression and increased the chemosensitivity of paclitaxel-resistant gastric cancer cells. Further investigation demonstrated that differential methylation of CpG islands neighboring the miR-34c promoter regulated the expression of miR-34c-5p in gastric cancer cell lines. Conclusions: DNA methylation, dysregulation of miR-34c-5p, and MAPT expression are critical factors in the chemoresistance of gastric cancer to paclitaxel. © 2013 Springer-Verlag Berlin Heidelberg.

Wu H.,Nanjing Medical University | Huang M.,Nanjing Medical University | Cao P.,Jiangsu Province Institute of Traditional Chinese Medicine | Wang T.,Nanjing Medical University | And 2 more authors.
Cancer Biology and Therapy | Year: 2012

The role of tumor suppressors and cell cycle factors in gastric carcinogenesis are well understood; however, the posttranscriptional changes that affect gene expression in gastric cancer are poorly characterized. MiR-135a has been shown to play a role in Hodgkin lymphoma. The aim of this study was to investigate the expression and role of miR-135a in gastric cancer. Quantitative real-time PCR demonstrated that miR-135a expression is downregulated in the majority of human primary gastric cancer tissues (8/11; 73%), compared with pair-matched adjacent non-tumor tissues. Furthermore, compared with the nonmalignant gastric cell line, GES -1, miR-135a expression was substantially downregulated in gastric cancer cell lines of various degrees of differentiation. Target analysis indicated miR-135a directly regulates Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase involved in cytokine receptor signaling pathways. Overexpression of miR-135a significantly downregulated the expression of JAK2 protein and also reduced gastric cancer cell proliferation and colony formation in vitro. MiR-135a-mediated JAK2 downregulation also reduced p-STAT3 activation and cyclin D1 and Bcl-x Lprotein expression. This study suggests that miR-135a may function as a tumor suppressor via targeting JAK to repress p-STAT3 activation, reduce cyclin D1 and Bcl-x L expression and inhibit gastric cancer cell proliferation. These results imply that novel treatment approaches targeting miR-135a may potentially benefit patients with gastric cancer. © 2012 Landes Bioscience.

Yang Y.,Jiangsu Province Institute of Traditional Chinese Medicine | Cai X.,Jiangsu Province Institute of Traditional Chinese Medicine | Yang J.,Jiangsu Province Institute of Traditional Chinese Medicine | Sun X.,Jiangsu Province Institute of Traditional Chinese Medicine | And 7 more authors.
Molecular Cancer | Year: 2014

Background: Nuclear factor-erythroid 2-related factor 2 (Nrf2) has emerged as a novel target for the prevention of colorectal cancer (CRC). Many chemopreventive compounds associated with Nrf2 activation are effective in preclinical systems and many on-going clinical trials are showing promising findings. In present study we evaluated the cytoprotective effect and chemopreventive properties of dietary digitoflavone.Method: A cell based Antioxidant Response Element (ARE)-driven luciferase reporter system was applied to screen potential Nrf2 activators. Activation of Nrf2 by digitoflavone was confirmed through mRNA, protein and GSH level assay in Caco-2 cell line. The cytoprotective effect of digitoflavone was evaluated in H2O2-induced oxidative stress model and further signaling pathways analysis was used to determine the target of digitoflavone induced Nrf2 activation. An AOM-DSS induced colorectal cancer model was used to assess the chemopreventive effect of digitoflavone.Result: Micromolarity (10 μM) level of digitoflavone increased Nrf2 expressing, nuclear translocation and expression of downstream phase II antioxidant enzymes. Furthermore, digitoflavone decreased H2O2-induced oxidative stress and cell death via p38 MAPK-Nrf2/ARE pathway. In vivo study, 50 mg/kg digitoflavone significantly reduced AOM-DSS induced tumor incidence, number and size.Conclusion: These observations suggest that digitoflavone is a novel Nrf2 pathway activator, and protects against oxidative stress-induced cell injury. The results of the present study add further evidence of the molecular mechanisms that allow digitoflavone to exert protective effects and reaffirm its potential role as a chemopreventive agent in colorectal carcinogenesis. © 2014 Yang et al.; licensee BioMed Central Ltd.

Zhou X.,State Key Laboratory of Coordination Chemistry | Cao P.,Jiangsu Province Institute of Traditional Chinese Medicine | Tian Y.,State Key Laboratory of Coordination Chemistry | Zhu J.,State Key Laboratory of Coordination Chemistry
Journal of the American Chemical Society | Year: 2010

Innovation in molecular diagnostics ultimately requires the conceptually distinct design of detection architectures. The diagnostic strategies reported thus far (planar/suspension arrays) suffer from either mass transport issues or limitations on the maximum number of targets that can be simultaneously detected. We report herein an expressed peptide assay scheme, by using nanoparticle probes, for detecting DNA hybridization events. The method exploits plasmid-encoded peptide tags as surrogate molecules for the matrix-assisted laser desorptlon/lonization time-of-flight mass spectrometry identification of target DNA. The binding of target DNA Is achieved through its recognition with a gold nanoparticle probe (functlonallzed with peptide-encoding plasmid and oligonucleotide complementary to part of the target sequence) and a microparticle probe (derivatized with oligonucieotide complementary to the rest of the target sequence). The magnetic separation of the three-component complex and expression of the peptide allows for the target identification by mass spectrometry. The detection of two DNA targets has been demonstrated through the selection of each individual tag for the respective target. Importantly, the modular nature of the probe design, by decoupling molecular binding events from peptide expression processes, should enable the ready extension of the methodology to the analysis of other species. An assay on a protein target has confirmed the efficacy of the conceptual framework proposed herein beyond the detection of DNA. The vast choice of mass tags offered by mass spectrometry provides significant advantages over previously documented assay systems. © 2010 American Chemical Society.

Yang J.,China Pharmaceutical University | Yang J.,Jiangsu Province Institute of Traditional Chinese Medicine | Cai X.,Jiangsu Province Institute of Traditional Chinese Medicine | Lu W.,Jiangsu Province Institute of Traditional Chinese Medicine | And 5 more authors.
Cancer Letters | Year: 2013

The activation of signal transducer and activator of transcription signaling 3 (STAT3) has been linked with the survival, proliferation, angiogenesis and immunosuppression of hepatocellular carcinoma cells (HCCs). Agents that can suppress STAT3 activation have potential to be cancer therapeutics. In this study, we investigated the inhibitory effect of evodiamine on STAT3 pathway in vitro and the anti-tumor effect of evodiamine in vivo in HCC. We found that evodiamine suppressed both constitutive and interleukin-6 (IL-6)-induced activation of STAT3 tyrosine 705 (Tyr705) effectively. The phosphorylation of Janus-activated kinase 2 (JAK2), Src and extracellular regulated protein kinases 1/2 (ERK1/2) were also suppressed by evodiamine. Interestingly, treatment of cells with sodium pervanadate abrogated the inhibition of evodiamine on IL-6-induced STAT3 (Tyr705) activation indicating the involvement of protein tyrosine phosphatases. Indeed, further studies demonstrated that evodiamine induced the expression of phosphatase shatterproof 1 (SHP-1). Moreover, inhibition of SHP-1 gene by small interference RNA abolished the ability of evodiamine to inhibit IL-6-induced STAT3 (Tyr705) activation. Evodiamine also suppressed STAT3 DNA binding activity and down-regulated the expression of STAT3-mediated genes leading to the suppression of proliferation, induction of cell apoptosis and cell cycle arrest. In vivo, evodiamine significantly inhibited tumor growth in a subcutaneous xenograft model with HepG2 cells. In summary, evodiamine blocked STAT3 signaling pathway by inducing SHP-1 and exhibited anticancer effect in vitro and in vivo. © 2012 Elsevier Ireland Ltd.

Pei H.,Jiangsu Province Institute of Traditional Chinese Medicine
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2012

To study the chemical constituents of seeds of Impatiens balsamina. The chemical constituents of the plant were isolated and purified by column chromatography and their structures were elucidated on the basis of physicochemical properties and spectral date. A new dinaphthofuran-7,12-dione derivative, named balsaminone C(1), with another two known dinaphthofuran-7,12-dione derivatives, balsaminone A (2), balsaminone B (3) were isolated. Compound 1 is a new compound. These compounds exhibit cytotoxicity against cancer cell lines A549, Bel-7402 and Hela. Compound 1 is worth to be further studied as potential anticancer agent.

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