ABSTRACT
The present study aimed to investigate the vasodilation effects of Allium macrostemon Bunge (AMB) on isolated rat pulmonary arterials (PAs) and to assess the underling mechanisms. The volatile oil was extracted by steam distillation from the bulbs of AMB. Then the volatile oil from AMB was studied on isolated rat PA, removal of endothelium, or pretreatment with nitro oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or with protein kinase A (PKA) inhibitor PKI but not cyclooxygenase inhibitor indomethacin significantly blocked the AMB induced relaxation on PE-contracted PA rings. AMB increased the phosphorylation level of NOS in a dose and time-dependent manner, which was through PKA activation. AMB dose-dependently increased the [Ca2+]i through Ca2+ influx in cultured pulmonary artery endothelial cells. A total of 18 components from the volatile oil of AMB were identified. The principle constituents of AMB, Dimethyl Disulfide (DMDS) but not Dimethyltrisulfide displayed dilation effects in PAs. Our results suggest that AMB induces relaxation in rat PAs via an endothelium-dependent mechanism involving Ca2+ entry, PKA dependent NOS phosphorylation and NO signaling. The vasodilator activities of AMB may through its constituent DMDS. The present study indicates therapeutic potentials of AMB on pulmonary hypertension.
Subject(s)
Allium/chemistry , Arterioles/drug effects , Disulfides/pharmacology , Oils, Volatile/pharmacology , Vasodilation , Vasodilator Agents/pharmacology , Animals , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/metabolism , In Vitro Techniques , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Phosphorylation , Rats , Rats, WistarABSTRACT
The aim of this study was to investigate the expression of circulating microRNAs (miRNAs) in apolipoprotein E (apoE) knockout mice (apoE(-/-)) and to validate the role of these miRNAs in human coronary artery disease (CAD). Pooled plasma from 10 apoE(-/-) mice and 10 healthy C57BL/6 (B6) mice was used to perform the microarray analysis. The results showed that miR-34a, miR-21, miR-23a, miR-30a and miR-106b were differentially expressed in apoE(-/-) mice, and these expression changes were confirmed by real-time quantitative reverse-transcription PCR. Then, miR-34a, miR-21, miR-23a, miR-30a and miR-106b were detected in the plasma of 32 patients with CAD and of 20 healthy controls. Only miR-34a, miR-21 and miR-23a were significantly differentially expressed in the plasma of CAD patients (all P<0.01). In conclusion, miR-34a, miR-21 and miR-23a were elevated in CAD patients, which means that these miRNAs might serve as biomarkers of CAD development and progression.
Subject(s)
Coronary Artery Disease/genetics , MicroRNAs/genetics , Aged , Animals , Apolipoproteins E/deficiency , Biomarkers , Case-Control Studies , Disease Models, Animal , Gene Expression Profiling , Gene Expression Regulation , Humans , Male , Mice , Mice, Knockout , Middle Aged , Pilot Projects , Reproducibility of Results , Risk FactorsABSTRACT
Flowers of Carthamus tinctorius L. are traditionally used in China to treat cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA), the main constituent of Carthamus tinctorius L. flowers, is known for its multiple biological activities. In the present study, HSYA was isolated from Carthamus tinctorius L. flowers by a macroporous resin adsorption chromatography method coupled with a Waters high-throughput auto-purification system and it's vasodilatation effects on pulmonary artery (PA) were explored by an assay of tension study on rat pulmonary artery (PA) rings. Results suggest that HSYA possesses vascular relaxation effects on rat PA by activating the KV channel in pulmonary vascular smooth muscle cells (PVSMCs).
Subject(s)
Carthamus tinctorius/chemistry , Chalcone/analogs & derivatives , Drugs, Chinese Herbal/pharmacology , Flowers/chemistry , Pulmonary Artery/drug effects , Quinones/pharmacology , Vasodilation/drug effects , Animals , Chalcone/chemistry , Chalcone/isolation & purification , Chalcone/pharmacology , China , Drugs, Chinese Herbal/chemistry , Female , Male , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Pulmonary Artery/metabolism , Quinones/chemistry , Quinones/isolation & purification , Rats , Rats, WistarABSTRACT
Semi-preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of oridonin from Isodon rubescens by using a two-phase-solvent system composed of n-hexane-ethyl acetate-methanol-water (2.8:5:2.8:5, v/v/v/v). The targeted compound isolated, collected and purified by HSCCC was analyzed by high performance liquid chromatography (HPLC). A total of 40.6 mg of oridonin with the purity of 73.5% was obtained in less than 100 min from 100 mg of crude Isodon rubescens extract. The chemical structure of the compound was identified by IR, 1H-NMR and 13C-NMR.
