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Ding X.,Nanjing Agricultural University | Zhu F.,Jiangsu Province Academy of Traditional Chinese Medicine | Yang Y.,Nanjing Agricultural University | Li M.,Nanjing Agricultural University
Food Chemistry | Year: 2013

Six steroidal glycoalkaloids (1-6) were isolated and purified from Solanum nigrum L. (SNL) by acid extraction and alkaline precipitation, various chromatographic techniques, and their structures were elucidated by spectroscopic data. Antitumor activity, structure-activity and its molecular mechanism were investigated by methyl thiazolyl tetrazolium (MTT) method, flow cytometry, colorimetric assay and an immunocytochemical method. Experimental results showed that compounds 1 (solasonine), 2 (β1-solasonine), 3 (solamargine) and 6 (solanigroside P) have cytotoxicity to MGC-803 cells. Compounds with three sugar units and a-L-rhamnopyranose at C-2 or a hydroxyl group on the steroidal backbone may be potential candidates for the treatment of gastric cancer. The mechanism of action may be related to the decrease of mutation p53, the increase of the ratio of Bax to Bcl-2 and the activation of caspase-3 to induce apoptosis. © 2013 Elsevier Ltd. All rights reserved.

Ding X.,Nanjing University | Zhu F.,Jiangsu Province Academy of Traditional Chinese Medicine | Gao S.,Nanjing University
Food Chemistry | Year: 2012

The water-extractable and the alkali-extractable polysaccharides from Solanum nigrum L. (named SNLWP and SNLAP, respectively) and their four polysaccharide sub-fractions (SNLWP-1, SNLWP-2, SNLAP-1 and SNLAP-2), were isolated and purified by ethanol precipitation, dialysis, anion-exchange and gel filtration chromatography. Antitumour and immunomodulatory activity of the polysaccharides was evaluated by determining the survival time, the ascites volume, the weight of immune organ and the level of cytokine (IL-2, IL-10 and IFN-γ) of H 22-bearing mice, respectively. The results showed that SNLWP-1, SNLAP-1 and SNLAP-2 had significant antitumour and immunomodulatory activity, whereas SNLWP-2 hardly demonstrated the activity. SNLWP-1 contained galactose and arabinose as main sugar components, and both SNLAP-1 and SNLAP-2 were rich in xylose, galactose and arabinose. SNLWP-2 was rich in glucose. In conclusion, SNLWP-1, SNLAP-1 and SNLAP-2 have potent antitumour activity which may be associated with their potent immunostimulating effect and monosaccharide composition. © 2011 Elsevier Ltd. All rights reserved.

Tong F.,Nanjing University | Tong F.,Institute of Hepatology | Cao P.,Jiangsu Province Academy of Traditional Chinese Medicine | Yin Y.,Jiang Nan University | And 3 more authors.
Digestive Diseases and Sciences | Year: 2014

Gastric carcinogenesis represents a stepwise progression from chronic inflammation to invasive adenocarcinomas and distant metastasis. It has been widely accepted that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-oncogenes and tumor suppressor genes. However, recent discoveries in microRNA research have reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. MicroRNAs (miRNAs) are a family of 18-25-nucleotide small RNAs that negatively regulate gene expression at the post-transcriptional level during various crucial cell processes such as apoptosis, differentiation and development. Changes in miRNA expression profiles have been observed in a variety of human tumors, including gastric cancer. Further studies demonstrated that miRNAs may function as tumor suppressors and oncogenes. These findings have shown great potential of miRNAs as a novel class of therapeutic targets. In addition, it was found that some miRNAs were directly involved in patients with gastric cancer, including prognosis prediction, treatment selection, and in the search for unknown primary sites. MiRNAs have also been proved to be detectable in serum and plasma. In this review, we summarize the function of miRNAs in gastric cancer. Furthermore, we describe the pathophysiological roles of these miRNAs and their clinical potential as diagnostic biomarkers and therapeutic targets. © 2013 Springer Science+Business Media New York.

Jiang T.,China Pharmaceutical University | Zhang Z.,Jiangsu Province Academy of Traditional Chinese Medicine | Zhang Y.,China Pharmaceutical University | Lv H.,China Pharmaceutical University | And 4 more authors.
Biomaterials | Year: 2012

Dual-functional liposomes with pH-responsive cell-penetrating peptide (CPP) and active targeting hyaluronic acid (HA) were fabricated for tumor-targeted drug delivery. A series of synthetic tumor pH-triggered CPPs rich in arginines and histidines were screened by comparing tumor cellular uptake efficiency at pH 6.4 with at pH 7.4, and R6H4 (RRRRRRHHHH) was obtained with the optimal pH-response. To construct R6H4-modified liposomes (R6H4-L), stearyl R6H4 was anchored into liposomes due to hydrophobic interaction. HA was utilized to shield positive charge of R6H4-L to assemble HA-coated R6H4-L (HA-R6H4-L) by electrostatic effect for protecting the liposomes from the attack of plasma proteins. The rapid degradation of HA by hyaluronidase (HAase) was demonstrated by the viscosity and zeta potential detection, allowing the R6H4 exposure of HA-R6H4-L at HAase-rich tumor microenvironment as the protection by HA switches off and cell-penetrating ability of R6H4 turns on. After HAase treatment, paclitaxel-loaded HA-R6H4-L (PTX/HA-R6H4-L) presented a remarkably stronger cytotoxicity toward the hepatic cancer (HepG2) cells at pH 6.4 relative to at pH 7.4, and additionally coumarin 6-loaded HA-R6H4-L (C6/HA-R6H4-L) showed efficient intracellular trafficking including endosomal/lysosomal escape and cytoplasmic liberation by confocal laser scanning microscopy (CLSM). In vivo imaging suggested the reduced accumulation of near infrared dye 15 (NIRD15)-loaded HA-R6H4-L (NIRD/HA-R6H4-L) at the tumor site, when mice were pre-treated with an excess of free HA, indicating the active tumor targeting of HA. Indeed, PTX/HA-R6H4-L had the strongest antitumor efficacy against murine hepatic carcinoma (Heps) tumor xenograft models in vivo. These findings demonstrate the feasibility of using tumor pH-sensitive CPPs and active targeting HA to extend the applications of liposomal nanocarriers to efficient anticancer drug delivery. © 2012 Elsevier Ltd.

Zhang Z.-H.,Jiangsu Province Academy of Traditional Chinese Medicine | Zhang Z.-H.,China Pharmaceutical University | Zhang Y.-L.,China Pharmaceutical University | Zhou J.-P.,China Pharmaceutical University | Lv H.-X.,China Pharmaceutical University
International Journal of Nanomedicine | Year: 2012

The aim of this study was to design and characterize solid lipid nanoparticles (SLNs) modified with stearic acid-octaarginine (SA-R8) as carriers for oral administration of insulin (SA-R8-Ins-SLNs). The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R8-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from -32.13 mV to 29.87 mV, by binding the positively charged SA-R8. Morphological studies of SA-R8-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R8 could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R8-Ins-SLNs increased the Caco-2 cell's internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R8-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R8-modifified SLNs promote the oral absorption of insulin. © 2012 Zeng et al, publisher and licensee Dove Medical Press Ltd.

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