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Dai G.-Y.,Nanjing University | Dai G.-Y.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Lv X.,Nanjing University | Lv X.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | And 6 more authors.
Chinese Traditional and Herbal Drugs | Year: 2016

Objective: To investigate the protective effect and the mechanism of loganin (an active component in Cornus officinalis) on the endoplasmic reticulum (ER) stress of glomerular mesangial cells (GMCs) induced by advanced glycation end products (AGEs). Methods: Human GMCs were cultured in vitro and divided into control group, model group (AGEs group), loganin group, and amino guanidine group (set as positive control, 0.1, 1.0, and 10.0 μmol/L). After being incubated with loganin (final concentration of 0.1, 1.0, and 10.0 μmol/L) for 1 h, GMCs were stimulated by AGEs (200 mg/L) for 24 h. Then, the cell proliferation was measured of using MTS method. PGE2 was investigated by Elisa. Receptors of advanced glycation end products (RAGE), and ER stress-related protein like GRP78, IRE1, XBP1, and inflammatory factor NF-κB and COX-2 in GMCs were detected by Western blotting. Results: Loganin could suppress the proliferation of GMCs induced by AGEs, improve the subcellular injury of GMCs, down-regulate the expression of ER stress-related protein GRP78, IRE1, XBP1, and RAGE, reduce the inflammation-related protein NF-κB, COX-2, and the level of PGE2. Conclusion: Loganin could improve the ER stress of GMCs induced by AGEs, lessen the inflammation and subcellular injury of GMCs, its mechanism might be related to the decreased expression of RAGE and the inhibition of the IRE1 pathway. © 2016, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Ni W.-T.,Nanjing University | Ni W.-T.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Pan Y.-H.,Nanjing University | Pan Y.-H.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | And 6 more authors.
Chinese Traditional and Herbal Drugs | Year: 2016

Activating blood and dissolving stasis is one of the important principles of clinical anti-tumor by traditional Chinese medicine and the anti-tumor effect of the blood-activating and stasis-resolving drugs has been confirmed by a large number of studies. But in recent years, some experimental studies have found that some blood-activating and stasis-resolving drugs could promote tumor metastasis. And then the clinical application of this kind of drugs has suffered from many controversial problems. Chinese materia medica (CMM) with breaking blood stasis and resolving mass (Poxue herbs) is a kind of blood-activating and stasis-resolving drugs which display the severe effect. Nowadays some researchers confirmed its obvious antineoplastic effect and its prominent anti-tumor metastasis effect, which indicated in recent studies. In this article, we summarized the anti-tumor metastasis effect and mechanism of the Poxue herbs like Curcumae Rhizoma, Sparganii Rhizoma, large blister Beetle, leech, and its effective components in detail. And we also put forward that Poxue herbs are the ones which have the anti-tumor metastasis effect among blood-activating and stasis-resolving drugs, and it valued with significant clinical application and development. It is also believed that the Poxue herbs could inhibit the tumor metastasis which is related with aerobic glycolysis and can provide the theoretical direction to guide clinical application. © 2016, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Xu W.,Nanjing University | Ying S.,Nanjing University | Peiliang S.,Nanjing University | Hongyan W.,Nanjing University | And 7 more authors.
Tumor | Year: 2015

The research on tumor metabolism has become a new hotspot in recent years, of which the key regulatory molecules that mediating tumor metabolism are a priority for all. The transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) is one of these key regulatory molecules. PGC-1α has been demonstrated to be a crucial regulatory molecule involved in a variety of metabolic diseases. It is also a key molecule in regulation of tumor metabolism, mediating oxidative metabolism and anabolism to participate in regulation of survival, proliferation and migration of tumor cells. This paper reviews the advances in research on structure of PGC-1α and its related transcription molecules, and explores the mechanism of PGC-1α in regulation of occurrence and development of tumors, especially focuses on advances in the role of PGC-1α in tumor metabolism, which may provide theoretical references for fundamental studies on antitumor metabolism based on PGC-1α target as well as the related drug development. © 2015 by TUMOR All rights reserved.

Li W.D.,Nanjing University | Wu Y.,Nanjing University | Zhang L.,Anhui Provincial Hospital | Yan L.G.,Nanjing University | And 11 more authors.
Phytomedicine | Year: 2013

Anti-cancer investigations on Xanthatin mainly focus on in vitro experiments. We herein reported the anti-tumor effects of Xanthatin both in vitro and in vivo. MTS assay results showed that Xanthatin had a remarkable anti-proliferative effect on B16-F10 cells. Moreover, the expression of β-catenin was up-regulated both in vitro and in vivo. Animal studies further revealed that Xanthatin killed the tumor cells around the blood vessels which contributes to reduce microvascular density extremely. All these results indicate that Xanthatin inhibited murine melanoma B16-F10 cell proliferation possibly associated with activation of Wnt/β-catenin pathway and its activity against melanoma tumor might also be relevant to inhibition of angiogenesis. © 2013 Elsevier GmbH. All rights reserved.

Wang A.-Y.,Nanjing University | Wang A.-Y.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Tao L.,Nanjing University | Lu Y.,Nanjing University | And 5 more authors.
Chinese Traditional and Herbal Drugs | Year: 2015

Diseases with excessive angiogenesis such as tumors need to be treated with anti-angiogenesis agents, while ischemic diseases need to be treated with pro-angiogenesis agents. Salviae Miltiorrhizae Radix et Rhizoma, the representative drug which promotes circulation and resolves clots, was widely used in treating tumors and ischemic diseases. This review focused on the current research on the angiogenic effect of Salviae Miltiorrhizae Radix et Rhizoma and its water-soluble or fat-soluble components. It was found that there are some controversy reports. Both pro-angiogenic and anti-angiogenic effects of Salviae Miltiorrhizae Radix et Rhizoma and its components have been reported. The major difference between tumor and ischemia is the maturity and stability of vessels. Angiogenesis is a complex process involving many signaling molecules. Therefore, the components of Salviae Miltiorrhizae Radix et Rhizoma will regulate the levels and functions of angiogenesis, and then vessels produce different maturity and stability. Overall, such controversy may be caused by differences in experimental conditions, the diversity of Salviae Miltiorrhizae Radix et Rhizoma components, the complexity of the angiogenic process, and the differences of drug distribution under different pathological states in vivo. ©, 2015, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

Liu Z.,Nanjing University | Zhu P.,Nanjing University | Zhu P.,Yangzhou University | Tao Y.,Nanjing University | And 16 more authors.
Food and Chemical Toxicology | Year: 2015

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. © 2015 Elsevier Ltd.

Ruan J.-S.,Nanjing University | Ruan J.-S.,Fujian Medical University | Liu Y.-P.,Nanjing University | Zhang L.,Nanjing University | And 8 more authors.
Acta Pharmacologica Sinica | Year: 2012

Aim:To investigate whether luteolin, a highly prevalent flavonoid, reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal.Methods:Murine malignant melanoma B16F10 cells were exposed to 1% O 2 for 24 h. Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay, respectively. EMT-related proteins, such as E-cadherin and N-cadherin, were examined using Western blotting. Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×10 6 cells in 0.2 mL per mouse) via the lateral tail vein. The mice were treated with luteolin (10 or 20 mg/kg, ip) daily for 23 d. On the 23rd day after tumor injection, the mice were sacrificed, and the lungs were collected, and metastatic foci in the lung surfaces were photographed. Tissue sections were analyzed with immunohistochemistry and HE staining.Results:Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips, which was accompanied by increased cellular adhesion and invasion. Luteolin (550 μmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner. Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation), which was reversed by luteolin (5 μmol/L). In B16F10 cells, luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway. In experimental metastasis model mice, treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%. Furthermore, the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues.Conclusion:Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3 integrin, suggesting that luteolin may be applied as a potential anticancer chemopreventative and chemotherapeutic agent. © 2012 CPS and SIMM.

Dong X.-P.,Nanjing University | Dong X.-P.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Ruan M.,Institute of Medicinal Fungi | Yu B.,Nanjing University | And 6 more authors.
Chinese Traditional and Herbal Drugs | Year: 2012

Objective: To study the concentration of geniposide in brains of rats ig administrated with borneol at different doses. Methods: Rats were ig administrated with 0.05, 0.1, 0.2, and 0.4 g/kg of borneol, and then iv injected with 300 mg/kg of geniposide. After 0.5, 1, 5, 10, 15, 30, 45, 60, and 90 min of geniposide injection, blood and brain tissue were collected, and the concentration of geniposide in the plasma and brain tissue was detected by RP-HPLC. The pharmacokinetic parameters of geniposide in plasma and brain tissue were analyzed by 3P97 software, and the relative bioavailability and brain target-correlated parameters of geniposide were calculated. Results: Pharmacokinetics of geniposide in plasma and brain tissue was accorded with two-compartment model. After treated with borneol, Cmax and AUC of geniposide in brain tissue were increased, MRT was prolonged, and tmax was shortened. Besides, borneol with dose of 0.2 g/kg had the most significant effect. Conclusion: Borneol could increase the quantity and velocity of geniposide permeating the blood-brain barrier and the effect will be most obvious when the dose of borneol is 0.2 g/kg.

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