Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica

Nanjing, China

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica

Nanjing, China
SEARCH FILTERS
Time filter
Source Type

Zhang D.-N.,Nanjing University | Guo Y.,Nanjing University | Li Z.-Q.,Nanjing University | Li W.,Nanjing University | And 3 more authors.
Chinese Pharmacological Bulletin | Year: 2012

Aim: To examine the effect of liguzinediol on ventricular remodeling induced by pressure overload in rats, as well as to explore the mechanisms involved. Methods: The model rats in which ventricular remodeling was induced with abdominal aortic banding (AAB) were randomly divided into 6 groups: Sham group, AAB model group, AAB plus Captopril group (10 mg·kg-1), AAB plus liguzinediol groups with various dosages(5,10 and 20 mg·kg -1). After administration of the tested drugs for 8 weeks, SBP, DBP, MAP, LVSP, LVEDP and ± dp/dtmax were recorded. Heart mass index (HMI) and left ventricular mass index(LVMI) were calculated. Isolated rat hearts were observed by hematoxylin-eosin(HE) staining. The concentrations of renin, angiotensin II(Ang II) and aldosterone(ALD) in plasma were measured by radioimmunoassay. The content of myocardial tissue hydroxyproline(HYP) was detected by alkaline hydrolysis, and the ratio of I/III type collagen was examined by ELISA. Results: Compared with model group, liguzinediol groups could significantly decrease hemodynamic parameters, HMI and LVMI, improve pathological changes, reduce Ang II and ALD content in left ventricular tissue, decrease HYP content and the ratio of I/III type collagen. Conclusion: In conclusion, liguzinediol significantly attenuates ventricular remodeling induced by pressure overload in rats. The beneficial mechanisms are in part associated with its alleviating the activation of renin-angiotensin-aldosterone system.


Xu B.-H.,Nanjing University | Xu B.-H.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Shen X.-C.,Guiyang Medical University | Zhang L.,Nanjing University | And 5 more authors.
Chinese Pharmacological Bulletin | Year: 2012

Aim: To observe the effect of Sal B on proliferation, migration and tube formation in vitro, discuss the influence on the neovascularization and find out the mechanism. Methods: Tritium-labeled thymidine ( 3H-TdR) method was used to determine the effect of Sal B on the proliferation of HUVECS. HUVECS migration was detected by Transwell assay. Capillary was detected by Matrigel-plug assay in vitro. Enzyme-linked immunosorbent assay (ELISA) and Western blot method were used to determine the effect of Sal B on the content of VEGF secreted by HUVECS and the expression of VEGF, respectively. Results: 3H-TdR assay showed that Sal B promoted the proliferation of HUVECS. The Transwell assay showed that Sal B accelerated the migration of HUVECS. The tube formation assay showed that the tube number and the length of the tube were higher than control group. After the HUVECS were treated by Sal B, the concentrations of VEGF were higher in cellular supernatant and the expression of VEGF was significantly up-regulated compared with the control group. Conclusion: Sal B promotes the proliferation, migration and tube-like structure formation. Its mechanism may be related to the up-regulation of VEGF expression.


Zhou L.,Nanjing University | Zhang K.,Nanjing University | Li J.,Hunan University | Cui X.,Nanjing University | And 7 more authors.
Reproductive Toxicology | Year: 2013

The use of herbal medicine has rapidly increased in recent decades, prompting an increase in toxicity concerns. Here we investigated whether and how essential oil of Curcuma zedoaria may induce reproductive and developmental toxicity. Whole embryo culture in rats revealed that the essential oil produced a concentration-dependent toxicity ex vivo in the embryos on gestation Day 9.5 (GD9.5). Weight loss, abnormal hematological and biochemical effects on dams and embryos were also observed in GD17 pregnant rats orally administrated with 100mgkg-1 or 200mgkg-1 essential oil from GD7 onward. Induction of embryotoxicity may be related to placental calcification attributed to inhibition of vascular endothelial growth factor (VEGF)-mediated angiogenesis. Analysis by gas chromatography-mass spectrometry demonstrated that the main toxic compounds in essential oil were sesquiterpenoids. Our results suggest that the reproductive toxicity of C. zedoaria may be caused by sesquiterpenoids in the essential oil blocking VEGF-mediated angiogenesis. © 2013 Elsevier Inc.


Zhang Z.-L.,Nanjing University | Zhang S.,Nanjing University | Guo Y.,Nanjing University | Wang Y.-Q.,Nanjing University | And 5 more authors.
Chinese Pharmacological Bulletin | Year: 2013

Aim: To explore the role of cannabinoid receptors in the activation of hepatic stellate cells (HSCs) and the interfering effects of curcumin in the hope of providing basis for elucidating the mechanism of liver fibrosis and curcumin inhibition of liver fibrosis. Methods: Influence of CBR1 agonist NADA and antagonist AM630, CBR2 agonist JWH015 and antagonist AM251 on the proliferation of HSCs was evaluated by MTT assay. Western blot assays were used to detect the expression of ERK, JNK and p38 and their phosphorylation levels in HSCs treated with AM251. The effect of curcumin on the expression of two types of cannabinoid receptors CBR1 and CBR2 in HSCs was determined by Western blot and immunofluorescence. The effect of curcumin on extracellular matrix (ECM) components αl (I) collagen and fibronectin in HSCs stimulating by CBR1 agonist and antagonist was also examined by Western blot. Results: Activating CBR1 promoted the proliferation of HSCs; on the contrary, CBR1 antagonism inhibited HSCs proliferation (P < 0. 05). At the same time, activating CBR2 also inhibited the proliferation of HSCs (P < 0. 05), but CBR2 inhibition had no apparent effect on the proliferation of HSCs(P >0.05). CBR1 antagonist AM251 significantly inhibited the phosphorylation of ERK and JNK in a dose-dependent manner (P < 0. 05, P < 0. 01), but p38 was not affected (P > 0. 05). Curcumin inhibited the expression of CBR1 (P < 0. 05), but at the same time, it had no significant effect on CBR2 (P > 0. 05). Curcumin inhibited the expression of ECM components upregulated by CBR1 agonist dose-dependently in HSCs, and collaboratively inhibited the expression of ECM components in HSCs exposed to CBR1 antagonist (P < 0. 05, P < 0. 01). Conclusions: Cannabinoid receptors play an important role in the process of HSCs activation. Curcumin may achieve the purpose of treating liver fibrosis through the intervention of cannabinoid receptor pathways.


Wu Y.-H.,Nanjing University | Wu Y.-H.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | Chen Y.-P.,Nanjing University | Chen Y.-P.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica | And 9 more authors.
Chinese Pharmacological Bulletin | Year: 2016

Aim: To explore the protective effect of loganin (an active component in Cornus officinalis) on podocyte injury induced by advanced glycation end products (AGEs) and its possible mechanism. Methods: Mouse podocytes were cultured in vitro and divided into Normal group, model group (AGEs group), loganin group and aminoguanidine group (set as positive control). After being incubated with loganin (final concentrations are 0.1, 1, 10 μmol · L-1) for 1 h, podocytes were stimulated by AGEs of 100 mg · L-1 for 24 h. Then, the cell viability was measured by using MTT method. Podocytes apoptosis was evaluated by Hoechst33342/PI staining and flow cytometry. Receptors of advanced glycation end products (RAGE), desmin and apoptosis-related protein like Bax, Bcl-2, cleaved caspase-3 in podocytes were detected by Western blot. Results: Loganin ameliorated podocyte injury induced by AGEs, down-regulated the expression of desmin and RAGE. Loganin also reduced the apoptotic rate of podocytes and decreased the ratio of Bax/Bcl-2 and the expression of pro-apoptotic protein cleaved caspase-3 in podocytes. Conclusion: Loganin could ameliorate podocyte injury, and its mechanism may be related to the decrease of the expression of RAGE and inhibition of the apoptotic pathway.


Yin Q.-Y.,Nanjing University | Guo J.,Nanjing University | Meng Q.-H.,Nanjing University | Li Y.,Nanjing University | And 2 more authors.
Chinese Pharmacological Bulletin | Year: 2013

Aim: To observe the effect of Liuweidihuang Formula (LWDHF) medicated serum on H2O2-injured human umbilical vascular endothelial cells (HUVECs) and elucidate its possible mechanism. Methods: HUVECs were injured by H2O2 with concentration of 400 μmol·L-1. Cell viability was determined using MTT assay. The morphological changes of chromosome were observed by invert fluorescent microscope. Apoptosis was determined using flow cytometry. The expression levels of Bax, Bcl-2, Caspase-3 mRNA and protein were measured by RT-PCR and Western blot, respectively. Results: Treatment with LWDHF medicated serum significantly increased the proliferation of HUVECs and reversed cell apoptosis. H 2O2 (400 μmol·L-1) significantly induced up-regulation of Bax and caspase-3 mRNA and protein levels which could be blocked by LWDHF. Treatment with LWDHF enhanced both mRNA transcription and protein expression of Bcl-2. Conclusion: LWDHF medicated serum protects HUVECs against apoptosis induced by H2O2, via up-regulation of Bcl-2 expression and down-regulation of the expression of Bax and caspase-3.


Shen C.-S.,Nanjing University | Fan F.-T.,Nanjing University | Tao L.,Nanjing University | Chen W.-X.,Nanjing University | And 4 more authors.
Chinese Pharmacological Bulletin | Year: 2013

PTEN is a tumor suppressing gene with phosphatase activity. It is one of the members of the dual specificity protein phosphatase family (DSPs). And it has both lipid phosphatase and protein tyrosine phosphatase activity. In the process of tumor proliferation, invasion and migration, increasing attentions have been directed towards tumor angiogenesis as a key factor in tumorigenesis. Tumor suppressing gene PTEN regulates expression of H1F-1, MMPs, VEGF, NHERF-1 and other angiogenesis-related signals and oxidative product by affecting the PI3K/Akt signaling pathway, which further impacts tumor angiogenesis. This article reviews the current research status based on the relationship between PTEN and tumor angiogenesis.


Kuai M.,Nanjing University | Li Y.,Nanjing University | Sun X.,Nanjing University | Ma Z.,Nanjing University | And 8 more authors.
Biomedicine and Pharmacotherapy | Year: 2016

Aims Sang-Tong-Jian (STJ), a novel formula composed of flavonoids and alkaloids derived from mulberry leaf, has been found to reduce blood glucose levels in rats with type 2 diabetes mellitus (T2DM) in our previous studies. However, the precise mechanisms remain unknown. Insulin resistance is the main characteristic of T2DM, which may be due to impairment of the PI3K/AKT signaling pathway. In this study, we investigated the effects of STJ on glycometabolism and insulin resistance in KKAy mice. Methods A total of 50 KKAy male mice were randomly divided into five groups: model, metformin at 260 mg/kg, and STJ at 105, 210 and 420 mg/kg. C57BL/6J mice were used as the control group. Random blood glucose levels in KKAy mice were determined every 10 days after treatments. At the 10th and 13th week, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted after a 12 h overnight fast, respectively. After 13-week treatments, glycosylated hemoglobin (GHb) and serum insulin were measured using a colorimetric method and ELISA kits. Liver glycogen and muscle glycogen levels were analyzed using a colorimetric method. The morphology of pancreas, liver, skeletal muscle and epididymal fat were visualized by haematoxylin and eosin staining. The gene level of GLUT2 (liver) and GLUT4 (skeletal muscle, epididymal fat) were detected by real-time PCR. The proteins of GLUT2, GLUT4, IRS1, PI3K, AKT and their phosphorylation were assayed by Western blot analyses. Results STJ significantly decreased the random blood glucose and GHb levels, and increased liver and muscle glycogen levels. The results of OGTT and ITT and measurement of serum insulin indicated that STJ ameliorated insulin resistance in KKAy mice. STJ treatments also ameliorated the histopathological alterations in pancreas, liver, skeletal muscle and epididymal fat in KKAy mice. Furthermore, STJ upregulated the gene and protein expression of GLUT2 (liver) and GLUT4 (skeletal muscle, epididymal fat). Meanwhile, GLUT4 translocation and phosphorylation of IRS1, p85-PI3K and AKT were significantly increased by STJ treatments. Conclusions Our results indicated that STJ ameliorated glycometabolism and insulin resistance in KKAy mice, which might be due to activation of PI3K/AKT pathway. © 2016 Elsevier Masson SAS


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.

Loading Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica collaborators
Loading Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica collaborators