Jiangsu Provincial Institute of Traditional Chinese Medicine

Nanjing, China

Jiangsu Provincial Institute of Traditional Chinese Medicine

Nanjing, China
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Ding Y.-F.,Nanjing University | Ding Y.-F.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Peng Y.-R.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Li J.,Jiangsu Provincial Institute of Traditional Chinese Medicine | And 3 more authors.
Journal of Pharmacy and Pharmacology | Year: 2013

Objectives The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism. Methods Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-β1, TGFβ receptor (TGFβR)I, TGFβRII, P-Smad2/3 and Smad7 were determined by Western blot. Results GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-β1, TGFβRI, TGFβRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats. Conclusions GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-β1 signalling pathway. © 2013 Royal Pharmaceutical Society.


Peng Y.-R.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Ding Y.-F.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Wei Y.-J.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Shu B.,Nanjing University of Technology | And 2 more authors.
Phytotherapy Research | Year: 2011

Caudatin-2,6-dideoxy-3-O-methy-β-d-cymaropyranoside (CDMC), the C-21 steroidal glycoside recently extracted from the traditional Chinese medicinal plant, the root of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae), has been shown to possess potent antitumor properties. However, the bioactivities of CDMC are still largely unknown, especially the antitumor effect and its mechanism. This study investigated the CDMC antitumor effects on human hepatoma cell line SMMC7721 cells by analysis of cell viability, cell cycle phases and apoptosis. The results showed that CDMC inhibited the growth of SMMC7721 cells in a time- and dose-dependent manner and resulted in cell cycle arrest in G 0/G 1 phase. Furthermore, CDMC induced SMMC7721 cell apoptosis rather than necrosis through caspase 3 activation, and a caspase 3 inhibitor, Ac-DEVD-CHO, could attenuate the apoptosis induced by CDMC. The results suggested that the anticancer activity of CDMC could be attributed partially to its inhibition of cell proliferation and induction of apoptosis associated with caspase 3 activation. © 2010 John Wiley & Sons, Ltd.


Jiang L.,Nanjing University | Jiang L.,Hainan Medical University | Wang Q.,Nanjing University | Shen S.,Nanjing University | And 3 more authors.
Thrombosis Research | Year: 2014

Introduction Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Materials and Methods Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Results Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC 50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P < 0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Conclusions Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. © 2013 Elsevier Ltd.


PubMed | Jiangsu Provincial Institute of Traditional Chinese Medicine and Nanjing University
Type: Journal Article | Journal: Chinese journal of natural medicines | Year: 2015

Drug-drug interactions have become a serious problem in the clinic, since plant-based medicines are extensively used. The present study investigated the effects of Ziziphus jujuba fruit (ZJ) extract on the pharmacokinetics of phenacetin, a typical substrate of a cytochrome P450 enzyme CYP 1A2, in rats. The rats were pretreated with the water extract (1.0 g kg(-1)) or the ethanolic extract (3.6 g kg(-1)) of ZJ for 10 days, and the pharmacokinetics of phenacetin was investigated after intravenous administration. In an in vitro assay, acetaminophen formation in the hepatic microsomes of ZJ-treated rats was investigated to assess CYP1A2 activity. Our results demonstrated that the treatment with the water and ethanolic extracts of ZJ decreased the plasma concentration of phenacetin and increased the plasma concentration of acetaminophen, resulting in a 43.2% and 15.5% reduction in the AUC0-120 of phenacetin, respectively, and a 53.2% and 64.9% increase in the AUC0-120 of acetaminophen, respectively after intravenous administration. The water or ethanolic extract of ZJ significantly increased the clearance of phenacetin and acetaminophen formation in hepatic microsomes. In conclusion, ZJ extracts displayed effects on the pharmacokinetics of phenacetin and increased the CYP1A2 activity in rats. Therefore, precaution on drug-drug interactions should be taken when ZJ is co-administered with drugs metabolized by CYP1A2, which may result in decreased concentrations of these drugs.


Peng Y.R.,Jiangsu Provincial Institute of Traditional Chinese Medicine
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To investigate nourishing-yin effect and mechanism of different parts of Cornu Elaphuri Davidiani in rats. The model of yin asthenia rats was built by thy roxine. The substance metabolism, pain threshold, hormone levels and biochemical indicators in serum were measured. The ethanol extract of Cornu Elaphuri Davidiani could regulate the substance metabolism and raise the pain threshold in yin asthenia model rats. Furthermore, it could regulate the hormone levels, biochemical indicators in serum and it could improvte the antioxidant ability. The ethanol extract of Cornu Elaphuri Davidiani showed significant nourishing-yin effect in rats and the possible mechanism is correlated with regulating the neuroendocrine network.


Peng Y.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Ding Y.,Jiangsu Provincial Institute of Traditional Chinese Medicine
Molecules | Year: 2015

Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine "baishouwu", which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-∞), mean residence time (MRT0-t and MRT0-∞), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease. © 2015 by the authors; licensee MDPI.


Wang Y.-H.,China Pharmaceutical University | Qiu C.,China Pharmaceutical University | Wang D.-W.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Hu Z.-F.,China Pharmaceutical University | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

Sheng-Mai San (SMS), a traditional Chinese medicine formula, has been used for the treatment of cardiovascular disease in Asia over long period of time. While its effectiveness has been confirmed by clinical use, its active chemical constituents remain unclear. In this paper, an HPLC-DAD-MS/MS method is described for the efficient and rapid identification of the chemical constituents in SMS extract. MS/MS fragmentation behavior of authentic compounds was proposed for aiding the structural identification of the components. A total of 53 compounds were identified or tentatively characterized by comparing their retention times, UV and MS spectra with those of authentic compounds or literature data. HPLC/UV and MS techniques were employed to screen for the potential bioactive components in rat plasma after oral administration of SMS. Twenty-five compounds including 14 prototype components and 11 metabolites were detected in dosed rat plasma compared with blank rat plasma. This identification and structural elucidation of the chemical constituents in the medicine formula and rat plasma may provide important experimental data for further pharmacological and clinical research. © 2010 Elsevier B.V.


Li F.,China Pharmaceutical University | Wang D.,Jiangsu Provincial Institute of Traditional Chinese Medicine | Xu P.,China Pharmaceutical University | Wu J.,Jiangsu Provincial Institute of Traditional Chinese Medicine | And 2 more authors.
Biomedical Chromatography | Year: 2013

Clematichinenoside AR (C-AR), a pentacyclic triterpenoid saponin with anti-inflammatory and anti-rheumatoid activities, is the main active component of the traditional Chinese medicine Clematidis Radix et Rhizoma. However, its poor oral absorption indicated that not only the parent compound C-AR itself, but also its metabolites could be responsible for the pharmacological effects in rats. The present study aimed to investigate the metabolism of C-AR in rat intestinal microflora, where C-AR was extensively metabolized. C-AR was incubated with the content of the large intestine. The culture solution was collected at different time points and analyzed for the metabolites of C-AR. Eight metabolites were identified by liquid chromatography/quadrupole time-of-flight mass spectrometry. M1, M2 and M5 were the major metabolites. In addition, it was proposed that deglycosylation was the only pathway contributing to the biotransformation of C-AR in rat intestinal microflora. © 2013 John Wiley & Sons, Ltd.


PubMed | Jiangsu Provincial Institute of Traditional Chinese Medicine
Type: Journal Article | Journal: Molecules (Basel, Switzerland) | Year: 2015

Caudatin is a potential antitumor agent isolated from the traditional Chinese medicine baishouwu, which was the root tuber of Cynanchum auriculatum Royle ex Wight. In our previous studies, caudatin showed selectivity on human hepatoma cell line SMMC7721 among several different tumor cell lines, and further in vivo tests validated the inhibitory action of caudatin against hepatic cancer using an H22 solid tumor model in mice, but to our knowledge, the biopharmaceutical properties of caudatin are largely unknown. In this study, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of caudatin in rat plasma and tissues, which kept the run time to detect one sample within 4 min, was developed and validated. Pharmacokinetics and tissue distribution studies of caudatin in conventional rats and hepatocellular carcinoma (HCC) model rats were then conducted for the first time. Statistically significant differences were observed between conventional rats and diethylnitrosamine (DEN)-induced HCC rats with respect to pharmacokinetic parameters, including maximum concentration (Cmax), time to reach Cmax (Tmax), half-life (t1/2), area under the concentration-time curve (AUC0-t, AUC0-), mean residence time (MRT0-t and MRT0-), and oral clearance (CL/F). Increased exposures of caudatin were found in the plasma and livers of HCC model rats, which would be helpful for a better understanding of pharmacological effect of caudatin in treating HCC disease.


PubMed | Chinese Academy of Sciences and Jiangsu Provincial Institute of Traditional Chinese Medicine
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2015

In our previous studies, caudatin-2,6-dideoxy-3-O-methy--d- cymaropyranoside (CDMC) was for the first time isolated from Cynanchum auriculatum Royle ex Wightand and was reported to possess a wide range of biological activities. However, the routes and metabolites of CDMC produced by intestinal bacteria are not well understood. In this study, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technique combined with Metabolynx(TM) software was applied to analyze metabolites of CDMC by human intestinal bacteria. The incubated samples collected for 48 h in an anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC-Q-TOF-MS within 12 min. Eight metabolites were identified based on MS and MS/MS data. The results indicated that hydrolysis, hydrogenation, demethylation and hydroxylation were the major metabolic pathways of CDMC in vitro. Seven strains of bacteria including Bacillus sp. 46, Enterococcus sp. 30 and sp. 45, Escherichia sp. 49A, sp. 64, sp. 68 and sp. 75 were further identified using 16S rRNA gene sequencing owing to their relatively strong metabolic capacity toward CDMC. The present study provides important information about metabolic routes of CDMC and the roles of different intestinal bacteria in the metabolism of CDMC. Moreover, those metabolites might influence the biological effect of CDMC in vivo, which affects the clinical effects of this medicinal plant.

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