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Man S.,Tianjin University | Gao W.,Tianjin University | Zhang Y.,Tianjin University of Traditional Chinese Medicine | Liu Z.,Tianjin University | And 3 more authors.
Cancer Biology and Therapy | Year: 2011

Formosanin C (FC) isolated from Rhizoma paridis, showed pro-apoptosis and immunoregulation with antitumor activity in cultured cells and animal systems. However, there is no report about its anti-metastatic effect on cancer cells. This research used the wound healing and the migration assay to detect the anti-invasive effect of FC on LA795 cells. Through the gelatin zymography assay and immunofluorescence analysis, FC showed suppression of enzyme activity of MMP-2 and MMP-9, and protein expression of MMP-1, -2, -3, -9 and -14 excreted from LA795 cells. Finally, FC exhibited much more effective inhibition of tumor growth and pulmonary metastasis in T739 mice than cisplatin did. Overall, the strong inhibition of MMP expression by FC might provide a potential therapeutic modality for lung tumors. © 2011 Landes Bioscience.

Liu Z.,Tianjin University | Wang J.,Tianjin University | Gao W.,Tianjin University | Man S.,Tianjin University of Science and Technology | And 2 more authors.
Pharmaceutical Biology | Year: 2013

Context: Saponins are active compounds in natural products. Many researchers have tried to find the method for knowing their concentration in herbs. Some methods, such as solid-liquid extraction and solvent extraction, have been developed. However, the extraction methods of the steroidal saponins from Paris polyphylla Smith var. yunnanensis (Liliaceae) are not fully researched. Objective: To establish a simple extraction method for the separation of steroidal saponins from the rhizomes of P. polyphylla Smith var. yunnanensis. Materials and methods: Macroporous adsorption resins were used for the separation of steroidal saponins. To select the most suitable resins, seven kinds of macroporous resins were selected in this study. The static adsorption and desorption tests on macroporous resins were determined. Also, we optimized the temperature and the ethanol concentration in the extraction method by the contents of five kinds of saponins. Then, we compared the extraction method with two other methods. Results: D101 resin demonstrated the best adsorption and desorption properties for steroidal saponins. Its adsorption data fits best to the Freundlich adsorption model. The contents of steroidal saponins in the product were 4.83-fold increased with recovery yields of 85.47%. Discussion and conclusion: The process achieved simple and effective enrichment and separation for steroidal saponins. The method provides a scientific basis for large-scale preparation of steroidal saponins from the Rhizoma Paridis and other plants. © 2013 Informa Healthcare USA, Inc.

Liu Z.,Tianjin University | Gao W.,Tianjin University | Liu C.,State Key Laboratories of Pharmacodynamics and Pharmacokinetics
Pharmaceutical Biology | Year: 2013

Context: Currently, famous traditional Chinese medicine formulas have undergone re-evaluation and development in China. Wei-Chang-An-Wan (WCAW) as one of them has been used for treating various gastrointestinal diseases for several decades. The secondary development of WCAW is in progress so as to interpret the effective material basis or find new pharmacological activity. Objective: To evaluate the antinociceptive effect of methanol extract of WCAW (ME) as well as four fractions (P.E., EtOAc, n-BuOH, H2O) and obtain information on the correlation between the contents of the fractions and antinociceptive effect. Materials and methods: ME was divided into four parts extracted by petroleum ether, ethyl acetate and n-butanol. Antinociceptive activity was evaluated by three models of acetic acid-induced writhing, formalin and hot-plate test in mice after repetitive administration of ME at 200, 400 or 800mg/kg, P.E. 132mg/kg, EtOAc 106mg/kg, n-BuOH 176mg/kg and H2O 176mg/kg for six days. The chemical compounds were analyzed by HPLC-ESI-MS. Results: ME at 800mg/kg inhibited acid-induced writhing by 84.69%, and reduced the licking time of second phase in formalin test by 53.23%. The inhibition rates in acid-induced writhing of P.E., EtOAc, n-BuOH and H2O were 27.79, 33.85, 38.97 and 37.69%, respectively, and in formalin test about 50%. They had no effect on the hot-plate test. HPLC-ESI-MS analysis showed that 68 chemical compounds were detected and 41 compounds were identified from ME. Discussion and conclusion: The results obtained herein indicate that WCAW possesses the antinociceptive activity that provides a new aspect in clinical application. © 2013 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

Qu Z.,Tianjin University | Zhang J.,College of Logistics | Gao W.,Tianjin University | Chen H.,College of Logistics | And 4 more authors.
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Cerebralcare Granule (CG), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Four Drugs". It has been used for treatment of cerebrovascular related diseases, such as hypertension. It is well known that vasodilatation plays a very important role in hypertensive. Despite the popular medicinal use of CG, little data was available to its activity and mechanism involved in vasodilatation. Therefore, we aimed to investigate the vasorelaxant effects of CG on isolated rat thoracic aorta so as to assess some of the possible mechanisms. The present study was performed to examine the vasodilative activity of CG and its mechanisms in isolated rat thoracic aorta. Materials and methods CG was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including NO synthase inhibitor NG-nitro-l- arginine methyl ester (l-NAME), cyclooxygenase (COX) inhibitor indomethacin (INDO), non-selective K+ channel inhibitor tetraethylammonium chloride (TEA), Kir channel inhibitor BaCl2, K ATP channel inhibitor Glibenclamide (Gli) and cholinergic receptor antagonist atropine were used, they were added 20 min before NE contraction and then added CG-induced vasodilation. Results Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NAME (0.1 mM) or INDO (0.01 mM) significantly blocked the CG induced relaxation. Pretreatment with the non-selective K+ channel inhibitor TEA (1 mM), or the Kir channel inhibitor BaCl2 (0.1 mM), neither of them had no influence on the CG-induced response (p>0.05). However, pretreatment with the K ATP channel inhibitor Gli (0.01 mM) produced significant inhibition on the CG-induced response (p<0.01). Besides, CG also inhibited the contraction triggered by NE in endothelium-denuded rings in Ca2+-free medium. CG (0.4, 0.8 and 3.2 mg/mL) produced rightward parallel displacement of CaCl2 curves and reduced the maximum contraction induced by 30 mM CaCl2 to 31.1±9.3%, 18.8±6.9% and 9.4±4.5%, respectively. The relaxation, induced by CG on endothelium-intact rat aortic rings pre-contracted with NE, was significantly attenuated in the presence of atropine (EC50=3.7 mg/mL, p<0.01). Conclusions Our results suggest that CG induces relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP pathway and an endothelium-independent pathway involving blockade of Ca2+ channels, inhibition of Ca2+ mobilization from intracellular stores, opening of KATP channel. In addition, the muscarinic receptor stimulation is also one of the vasorelaxant mechanisms. © 2014 Elsevier Ireland Ltd. All rights reserved.

Guo H.,Tianjin University | Zhang J.,College of Logistics | Gao W.,Tianjin University | Qu Z.,Tianjin University | Liu C.,State Key Laboratories of Pharmacodynamics and Pharmacokinetics
Pharmaceutical Biology | Year: 2014

Context: Radix Aucklandiae, the dry rhizome of Aucklandia lappa Decne (Asteraceae), enjoyed traditional popularity for its antidiarrheal effects. Although there are many investigations on its chemical constituents and pharmacologic actions, few studies explaining its activity and mechanism in gastrointestinal disorders are available. Objective: In this paper, we focused on the effects of the methanol extract of R. Aucklandiae (RA ext) on gastrointestinal tract, so as to assess some of the possible mechanisms involved in the clinical treatment. Materials and methods: In vivo, in neostigmine-induced mice and normal mice, after intragastric administration, RA ext (100, 200, 300, and 400 mg/kg) was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effect of it (0.1, 0.2, 0.3, and 0.4 mg/mL) on the isolated tissue preparations of rat jejunum was also investigated, as well as costunolide and dehydrocostuslactone which were the main constituents. Results: In vivo, the gastric emptying increased and intestinal transit decreased after the administration of RA ext in normal mice. However, RA ext inhibited the gastric emptying and the intestinal transit throughout the concentrations in neostigmine-induced mice. In vitro, RA ext caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in a dose-dependent manner ranging from 0.1 to 0.4 mg/mL, and it also relaxed the acetylcholine chloride (Ach, 10-5 M), 5-hydroxytryptamine (5-HT, 200 μM)-induced, and K+ (60 mM)-induced contractions. RA ext shifted the Ca2+ concentration-response curves to right, similar to that caused by verapamil (0.025 mM). The Ca2+ concentration-response curves were shifted by costunolide (CO) (5.4, 8.1, and 10.8 μg/mL), dehydrocostuslactone (DE) (4.6, 6.9, and 9.2 μg/mL), costunolide-dehydrocostuslactone (CO-DE) (5.4-4.6, 8.1-6.9, and 10.8-9.2 μg/mL) to the right, similar to that caused by verapamil (0.01 mM). Discussion and conclusion: These results indicate that RA ext played a spasmolytic role in gastrointestinal motility, which is probably mediated through the inhibition of muscarinic receptors, 5-HT receptors, and calcium influx. The presence of cholinergic and calcium antagonist constituents may be the compatibility of CO and DE. All these results provide a pharmacological basis for its clinical use in the gastrointestinal tract. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

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