Jiangsu Province Academy of Traditional Chinese Medicine

Nanjing, China

Jiangsu Province Academy of Traditional Chinese Medicine

Nanjing, China
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Ding X.,Nanjing University | Zhu F.-S.,Jiangsu Province Academy of Traditional Chinese Medicine | Li M.,Nanjing University | Gao S.-G.,Nanjing University
Journal of Ethnopharmacology | Year: 2012

Ethnopharmacological relevance: Solanum nigrum L. (SNL), a traditional Chinese medicinal herb endowed with diuretic, antipyretic and hepatoprotective effects, has been used as a major ingredient of folk prescriptions for anticancer treatment in China. Aim of the study: The purpose of this study was to evaluate the inhibitory effect of solamargine (SM), a major steroidal alkaloid glycoside purified from SNL, on human hepatoma SMMC-7721 cells and investigate the possible mechanism of SM. Materials and methods: The MTT assay was used to evaluate the IC 50 on tumor cell lines. The effect on morphology was observed with a light or fluorescence microscopy. The rate of apoptosis and the cell cycle were measured using flow cytometry (FCM). The expression of caspase-3 protein was measured by colorimetric assay. Results: SM significantly inhibited the growth of SMMC-7721 and HepG2 cells and induced cell apoptosis. Cell cycle analysis revealed that SM caused cell cycle arrest at the G2/M phase. Moreover, SM could up-regulate the expression of caspase-3. Conclusions: This study indicated that SM exerted potential anticancer activity on SMMC-7721 cells in vitro through the activation of caspase-3 and the regulation of the cell cycle progression to induce apoptosis and inhibit hepatoma cells proliferation. © 2011 Elsevier Ireland Ltd.

Lv H.-X.,China Pharmaceutical University | Zhang Z.-H.,Jiangsu Province Academy of Traditional Chinese Medicine | Hui-Jiang,Qilu Pharmacutical Co. | Waddad A.Y.,China Pharmaceutical University | Zhou J.-P.,China Pharmaceutical University
Pharmazie | Year: 2012

The aim of this study was to improve the solubility, stability and bioavailability of amorphous atorvastatin calcium (AT) by complexing it with hydroxypropyl-β-cyclodextrin. The formation of the inclusion complexation was identified by molecular modeling, phase solubility diagrams, differential scanning calorimetry and X-ray powder diffractometry. Orally Disintegrating Tablets (ODT) were then manufactured by direct compression. Apart from improved stability compared to pure AT, disintegration time of 27 s, hardness of 5 kg and favorable mouth feel were achieved. In vitro dissolution tests of the ODT of AT inclusion complex exhibited higher dissolution rates than those with pure drug and the commercial tablet Lipitor®. In vivo bioavailability studies in rats also showed shorter T max, higher C max and increased AUC of 4.42 and 1.86 fold compared to the plain drug ODT and Lipitor®. These results strongly suggest to use HP-β-CD to improve the physicochemical characteristics and bioavailability of AT.

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.

Xu J.-D.,Jiangsu Province Academy of Traditional Chinese Medicine | Mao Q.,Jiangsu Province Academy of Traditional Chinese Medicine | Shen H.,Jiangsu Province Academy of Traditional Chinese Medicine | Zhu L.-Y.,Jiangsu Province Academy of Traditional Chinese Medicine | And 2 more authors.
Journal of Chromatography A | Year: 2013

Qiong-Yu-Gao (QYG), consisting of Rehmanniae Radix (RR), Poriae (PO) and Ginseng Radix (GR), is a commonly used tonic traditional complex herbal medicine (CHM). So far, three different methods have been documented for preparation of QYG, i.e. method 1 (M1): mixing powders of GR and PO with decoction of RR; method 2 (M2): combining the decoction of RR and PO with the decoction of GR; method 3 (M3): decocting the mixture of RR, GR and PO. In present study, an ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical profiling approach was developed to investigate the influence of the three preparation methods on the holistic quality of QYG. All detected peaks were unambiguously identified by comparing UV spectra, accurate mass data/characteristic mass fragments and retention times with those of reference compounds, and/or tentatively assigned by matching empirical molecular formula with that of known compounds, and/or elucidating quasi-molecular ions and fragment ions referring to information available in literature. A total of 103 components, mainly belonging to ginsenosides, phenethylalcohol glycosides, iridoid glycosides and triterpenoid acids, were identified, of which 5 degraded ginsenosides were putatively determined to be newly generated during preparation procedures of QYG samples. Triterpenoid acids and malonyl-ginsenosides were detected only in M1 samples, while degraded ginsenosides were merely detectable in M2/M3 samples. The possible reasons for the difference among chemical profiles of QYG samples prepared with three methods were also discussed. It could be concluded that preparation method do significantly affect the holistic quality of QYG. The influence of the altered chemical profiles on the bioactivity of QYG needs further investigation. The present study demonstrated that UHPLC-PDA-QTOF-MS/MS based chemical profiling approach is efficient and reliable for evaluating the holistic quality of traditional CHM. © 2013 Elsevier B.V.

Tong F.,Nanjing University | Tong F.,Suzhou Fifth Peoples Hospital | 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.

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.

Mao Q.,Jiangsu Province Academy of Traditional Chinese Medicine | Zhang P.-H.,China Pharmaceutical University | Wang Q.,China Pharmaceutical University | Li S.-L.,Jiangsu Province Academy of Traditional Chinese Medicine
Phytomedicine | Year: 2014

Ginsenoside F2 (F2) is a potential bioactive metabolite of major ginsenosides. The potential anti-cancer effect of F 2 in gastric cancer cells has not been appraised. This study investigated the effects of F2 on the production of reactive oxygen species (ROS). We also investigated the in vitro and in vivo effects of F 2 on the downstream signaling pathways leading to apoptosis in human gastric cancer cells. The in vitro data revealed that F2 induces ROS accumulation followed by a decrease in mitochondrial transmembrane potential (MTP), and the release of cytochrome c (cyto c), which induced the caspase-dependent apoptosis. Further assay indicated that modulation of ASK-1/JNK pathway contributes to apoptosis. In vivo, F2 exhibits the obvious anti-cancer effect compared with cisplatin with no obvious toxicity. Jointly, these results suggest that F2 induces apoptosis by causing an accumulation of ROS and activating the ASK-1/JNK signaling pathway. This provides further support for the use of F2 as a novel anticancer therapeutic candidate. © 2013 Elsevier GmbH.

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.

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.

Wang P.J.,Jiangsu Province Academy of Traditional Chinese Medicine
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica | Year: 2012

To establish a non-invasive, repeatable and dynamic study method in endometriosis rat model using magnetic resonance imaging (MRI), in order to explore the magnetic resonance characteristics of the model. Endometrium tissues were transplanted into left abdominal walls of unmated adult female SD rats. After surgery, pathological changes were observed and MRI scanning was made for the ectopic lesions. The endometriosis rat model was successfully established and the ectopic lesions imaged strong hyperintense on DWI, hypointense on T1WI, hyperintense on T2WI with a clear border, without enhancement on CE-T1 WI. The lesions can be clearly observed in the MRI images on the endometriosis rat model established by this method, which facilitates repeat experiments and continuous observation studies.

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