The Experts below are selected from a list of 1515 Experts worldwide ranked by ideXlab platform
Jian Wang - One of the best experts on this subject based on the ideXlab platform.
-
Tanshinone IIA sulfonate protects against cigarette smoke induced copd and down regulation of cftr in mice
Scientific Reports, 2018Co-Authors: Jian Wang, Hua Jiang, Xuefang Gong, Dejun Sun, Jiaze Shu, Ziyi Wang, Zhen Long, Yiguan Chen, Zili Zhang, Liang YuanAbstract:Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline. The anti-inflammatory actions of Tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied. However, it remains unknown whether sodium Tanshinone IIA sulfonate (STS) protects against the development of COPD. Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10 μg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations. Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS.
-
Tanshinone IIA sulfonate protects against cigarette smoke-induced COPD and down-regulation of CFTR in mice
Nature Publishing Group, 2018Co-Authors: Jian Wang, Hua Jiang, Xuefang Gong, Dejun Sun, Jiaze Shu, Ziyi Wang, Zhen Long, Yiguan Chen, Zili ZhangAbstract:Abstract Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by abnormal inflammation, persistent and progressive lung function decline. The anti-inflammatory actions of Tanshinone IIA, which is the most important active component from Chinese herbal medicine Danshen, have been well studied. However, it remains unknown whether sodium Tanshinone IIA sulfonate (STS) protects against the development of COPD. Here we found that STS inhalation (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function decline, airspace enlargement, mucus production, bronchial collagen deposition, inflammatory responses and oxidative stress caused by cigarette smoke (CS) and lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10 μg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were associated with inhibition of ERK1/2 and NF-κB activations. Interestingly, STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-κB-dependent inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL-8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and down-regulation of CFTR are prevented by STS
-
Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway
Frontiers Media S.A., 2018Co-Authors: Ruijuan Guan, Jian Wang, Yuqin Chen, Tao Wang, Mingjing Ding, Qian Yang, Zhen LongAbstract:Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium Tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD
-
Tanshinone IIA inhibits lipopolysaccharide induced muc1 overexpression in alveolar epithelial cells
American Journal of Physiology-cell Physiology, 2014Co-Authors: Kedong Zhang, Jian Wang, Hua Jiang, Sheng Wang, Chenting Zhang, Xuefang GongAbstract:The anti-inflammatory function of Tanshinone IIA (TIIA), an active natural compound from Chinese herbal medicine Danshen, has been well recognized, and therefore TIIA has been widely used to treat ...
-
sodium Tanshinone IIA sulfonate inhibits canonical transient receptor potential expression in pulmonary arterial smooth muscle from pulmonary hypertensive rats
American Journal of Respiratory Cell and Molecular Biology, 2013Co-Authors: Jian Wang, Yi Zhang, Yuqin Chen, Kai Yang, Qian Jiang, Limei Wan, Elizabeth Wenqian Wang, Ning LaiAbstract:Danshen, the dried root of Salvia miltiorrhiza, is widely used in clinics in China for treating various diseases, including cardiovascular diseases. Sodium Tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca2+ concentration ([Ca2+]i) and store-operated Ca2+ entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn2+ quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O2, 21 d) was increased by 59%, and basal [Ca2+]i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. Thes...
Duxin Qing - One of the best experts on this subject based on the ideXlab platform.
-
Tanshinone IIA elicited vasodilation in rat coronary arteriole roles of nitric oxide and potassium channels
European Journal of Pharmacology, 2009Co-Authors: Guobao Wu, Enxiang Zhou, Duxin QingAbstract:Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of Tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of Tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated potassium channels (BKca) significantly decreased the vasodilation elicited by Tanshinone IIA. The results indicated that Tanshinone IIA induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca channels plays an important role in the vasodilation.
-
Tanshinone IIA elicited vasodilation in rat coronary arteriole roles of nitric oxide and potassium channels
European Journal of Pharmacology, 2009Co-Authors: Guobao Wu, Enxiang Zhou, Duxin QingAbstract:Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of Tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of Tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and potassium channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated potassium channels (BKca) significantly decreased the vasodilation elicited by Tanshinone IIA. The results indicated that Tanshinone IIA induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca channels plays an important role in the vasodilation.
Jian Hui Wu - One of the best experts on this subject based on the ideXlab platform.
-
antiandrogenic maspin induction and antiprostate cancer activities of Tanshinone IIA and its novel derivatives with modification in ring a
Journal of Medicinal Chemistry, 2012Co-Authors: Jinming Zhou, Guoyan Geng, Francoise Sauriol, Jian Hui WuAbstract:Expression of metastatic suppressor maspin is lost in advanced prostate cancer. Clinically relevant mutations in androgen receptor (AR) convert antiandrogens into AR agonists, promoting prostate tumor growth. We discovered Tanshinone IIA (TS-IIA) is a potent antagonist of mutated ARs and induces maspin expression through AR. TS-IIA suppressed AR expression and induced apoptosis in LNCaP cells. Syntheses of TS-IIA derivatives (1–9) revealed that the 4,4-dimethyl group at ring A is important for TS-IIA’s antiandrogenic and maspin induction activities.
-
antiandrogenic maspin induction and antiprostate cancer activities of Tanshinone IIA and its novel derivatives with modification in ring a
Journal of Medicinal Chemistry, 2012Co-Authors: Jinming Zhou, Guoyan Geng, Francoise Sauriol, Jian Hui WuAbstract:Expression of metastatic suppressor maspin is lost in advanced prostate cancer. Clinically relevant mutations in androgen receptor (AR) convert antiandrogens into AR agonists, promoting prostate tumor growth. We discovered Tanshinone IIA (TS-IIA) is a potent antagonist of mutated ARs and induces maspin expression through AR. TS-IIA suppressed AR expression and induced apoptosis in LNCaP cells. Syntheses of TS-IIA derivatives (1–9) revealed that the 4,4-dimethyl group at ring A is important for TS-IIA’s antiandrogenic and maspin induction activities.
Haiping Hao - One of the best experts on this subject based on the ideXlab platform.
-
pharmacokinetics absorption and tissue distribution of Tanshinone IIA solid dispersion
Planta Medica, 2006Co-Authors: Haiping Hao, Guangji Wang, Nan Cui, Lin Xie, Zuoqi DingAbstract:This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of Tanshinone IIA, a highly lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic characteristics, absolute bioavailability, tissue distribution and plasma protein binding properties were determined. The membrane permeability was evaluated using Caco-2 cells in monolayer. The pharmacokinetic plasma profile of Tanshinone IIA after a single intravenous dosing exhibited a triexponential pattern consisting of rapid distribution (t1/2 alpha, 0.024 h), slow redistribution (t1/2 beta, 0.34 h) and terminal elimination phase (t1/2 gamma, 7.5 h). Tanshinone IIA preferentially distributed into the reticuloendothelial system, especially into liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %) bound highly to plasma proteins, among which lipoprotein played an important role (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that the AUC and Cmax increased less proportionally to dose and Tmax was significantly prolonged. The poor absorption of Tanshinone IIA may be caused by its low aqueous solubility and limited membrane permeability. There were no significant differences of the apparent permeability coefficient for all tested concentrations and for the apical to basolateral and reverse direction transport, suggesting a passive transport mode and no involvement of an efflux protein. In conclusion, Tanshinone IIA has a suitable pharmacokinetic behavior except for its poor absorption. A pharmaceutical strategy for promoting its absorption should be designed to develop Tanshinone IIA as a new drug candidate.
-
characterization of metabolites of Tanshinone IIA in rats by liquid chromatography tandem mass spectrometry
Journal of Mass Spectrometry, 2006Co-Authors: Guangji Wang, Haiping Hao, Chaonan ZhengAbstract:The metabolism of Tanshinone IIA was studied in rats after a single-dose intravenous administration. In the present study, 12 metabolites of Tanshinone IIA were identified in rat bile, urine and feces with two LC gradients using LC-MS/MS. Seven phase I metabolites and five phase II metabolites of Tanshinone IIA were characterized and their molecular structures proposed on the basis of the characteristics of their precursor ions, product ions and chromatographic retention time. The seven phase I metabolites were formed, through two main metabolic routes, which were hydroxylation and dehydrogenation metabolism. M1, M4, M5 and M6 were supposedly Tanshinone IIB, hydroxyTanshinone IIA, przewaquinone A and dehydroTanshinone IIA, respectively, by comparing their HPLC retention times and mass spectral patterns with those of the standard compounds. The five phase II metabolites identified in this research were all glucuronide conjugates, all of which showed a neutral loss of 176 Da. M9 and M12 were more abundant than other identified metabolites in the bile, which was the main excretion path of Tanshinone IIA and the metabolites. M12 was the main metabolite of Tanshinone IIA. M9 and M12 were proposed to be the glucuronide conjugates of two different semiquinones and these semiquinones were the hydrogenation products of dehydroTanshinone IIA and Tanshinone IIA, respectively. This hydrogenized reaction may be catalyzed by the NAD(P)H: quinone acceptor oxidoreductase (NQO). The biotransformation pathways of Tanshinone IIA were proposed on the basis of this research.
-
simultaneous quantification of cryptoTanshinone and its active metabolite Tanshinone IIA in plasma by liquid chromatography tandem mass spectrometry lc ms ms
Journal of Pharmaceutical and Biomedical Analysis, 2006Co-Authors: Haiping Hao, Guangji Wang, Zuoqi DingAbstract:Abstract A rapid and sensitive method for the simultaneous determination of cryptoTanshinone and its active metabolite Tanshinone IIA in rat plasma was developed and well validated, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. This method entailed a single step of liquid–liquid extraction with ethyl acetate from a small volume of plasmas. The analytes and internal standard diazepam were baseline separated on a Shim-pack VP-ODS analytical column. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated under selected reaction monitoring (SRM) mode. The method was linear in the concentration range of 1–100 ng/ml for both Tanshinone IIA and cryptoTanshinone. The intra- and inter-day precisions (R.S.D.%) were within 10.2% for both analytes. Deviation of the assay accuracies was within ±12.0% for both analytes. Both analytes were proved to be stable during all sample storing, preparation and analytic procedures. The method was successfully applied to a pharmacokinetic study after an oral administration of cryptoTanshinone to rats with a dose of 20 mg/kg. With the lower limits of quantification at 1.0 ng/ml for Tanshinone IIA and 0.2 ng/ml for cryptoTanshinone, this method was proved to be sensitive enough and reproducible for the pharmacokinetics study of both Tanshinones.
Guangji Wang - One of the best experts on this subject based on the ideXlab platform.
-
pharmacokinetics absorption and tissue distribution of Tanshinone IIA solid dispersion
Planta Medica, 2006Co-Authors: Haiping Hao, Guangji Wang, Nan Cui, Lin Xie, Zuoqi DingAbstract:This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of Tanshinone IIA, a highly lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic characteristics, absolute bioavailability, tissue distribution and plasma protein binding properties were determined. The membrane permeability was evaluated using Caco-2 cells in monolayer. The pharmacokinetic plasma profile of Tanshinone IIA after a single intravenous dosing exhibited a triexponential pattern consisting of rapid distribution (t1/2 alpha, 0.024 h), slow redistribution (t1/2 beta, 0.34 h) and terminal elimination phase (t1/2 gamma, 7.5 h). Tanshinone IIA preferentially distributed into the reticuloendothelial system, especially into liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %) bound highly to plasma proteins, among which lipoprotein played an important role (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that the AUC and Cmax increased less proportionally to dose and Tmax was significantly prolonged. The poor absorption of Tanshinone IIA may be caused by its low aqueous solubility and limited membrane permeability. There were no significant differences of the apparent permeability coefficient for all tested concentrations and for the apical to basolateral and reverse direction transport, suggesting a passive transport mode and no involvement of an efflux protein. In conclusion, Tanshinone IIA has a suitable pharmacokinetic behavior except for its poor absorption. A pharmaceutical strategy for promoting its absorption should be designed to develop Tanshinone IIA as a new drug candidate.
-
characterization of metabolites of Tanshinone IIA in rats by liquid chromatography tandem mass spectrometry
Journal of Mass Spectrometry, 2006Co-Authors: Guangji Wang, Haiping Hao, Chaonan ZhengAbstract:The metabolism of Tanshinone IIA was studied in rats after a single-dose intravenous administration. In the present study, 12 metabolites of Tanshinone IIA were identified in rat bile, urine and feces with two LC gradients using LC-MS/MS. Seven phase I metabolites and five phase II metabolites of Tanshinone IIA were characterized and their molecular structures proposed on the basis of the characteristics of their precursor ions, product ions and chromatographic retention time. The seven phase I metabolites were formed, through two main metabolic routes, which were hydroxylation and dehydrogenation metabolism. M1, M4, M5 and M6 were supposedly Tanshinone IIB, hydroxyTanshinone IIA, przewaquinone A and dehydroTanshinone IIA, respectively, by comparing their HPLC retention times and mass spectral patterns with those of the standard compounds. The five phase II metabolites identified in this research were all glucuronide conjugates, all of which showed a neutral loss of 176 Da. M9 and M12 were more abundant than other identified metabolites in the bile, which was the main excretion path of Tanshinone IIA and the metabolites. M12 was the main metabolite of Tanshinone IIA. M9 and M12 were proposed to be the glucuronide conjugates of two different semiquinones and these semiquinones were the hydrogenation products of dehydroTanshinone IIA and Tanshinone IIA, respectively. This hydrogenized reaction may be catalyzed by the NAD(P)H: quinone acceptor oxidoreductase (NQO). The biotransformation pathways of Tanshinone IIA were proposed on the basis of this research.
-
simultaneous quantification of cryptoTanshinone and its active metabolite Tanshinone IIA in plasma by liquid chromatography tandem mass spectrometry lc ms ms
Journal of Pharmaceutical and Biomedical Analysis, 2006Co-Authors: Haiping Hao, Guangji Wang, Zuoqi DingAbstract:Abstract A rapid and sensitive method for the simultaneous determination of cryptoTanshinone and its active metabolite Tanshinone IIA in rat plasma was developed and well validated, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. This method entailed a single step of liquid–liquid extraction with ethyl acetate from a small volume of plasmas. The analytes and internal standard diazepam were baseline separated on a Shim-pack VP-ODS analytical column. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated under selected reaction monitoring (SRM) mode. The method was linear in the concentration range of 1–100 ng/ml for both Tanshinone IIA and cryptoTanshinone. The intra- and inter-day precisions (R.S.D.%) were within 10.2% for both analytes. Deviation of the assay accuracies was within ±12.0% for both analytes. Both analytes were proved to be stable during all sample storing, preparation and analytic procedures. The method was successfully applied to a pharmacokinetic study after an oral administration of cryptoTanshinone to rats with a dose of 20 mg/kg. With the lower limits of quantification at 1.0 ng/ml for Tanshinone IIA and 0.2 ng/ml for cryptoTanshinone, this method was proved to be sensitive enough and reproducible for the pharmacokinetics study of both Tanshinones.