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Objective To study the mangiferin absorption process of mangiferin polymorphs in SD rats thus to find out the optimal crystal form and explore the factors that may affect the clinical effects of mangiferin. Methods Each rat was given one of three crystal forms of mangiferin. Plasma concentration of mangiferin were determined by HPLC-MS method. After liquidliquid extraction by ethyl acetate, the chromatographic separation was carried out on an Agilent ZORBAX SB-C18 (2.1 mm× 100 mm,3.5 μm) with a mobile phase consisting of methanol-0.1％ formic acid aqueous solution (30:70) . Mass spectrometry were performed in positive ion mode. Ion mass-to-charge ratio was set at 445 and 447 for mangiferin and, cefuroxime sodium (internal standard) respectivel for quantitive analysis. Results The main pharmacokinetic parameters of mangiferin form II, Ⅴ, Ⅵ were as follows: AUC(0-24 h) were (1323. 27 ± 218. 07) ,(1974. 34 ± 469. 24) ,(1737. 79 ± 623. 06) ng · mL-1 · h, respectively; Cmax were (321.92±85.18) ,(455.83±277.07) ,(319.92±86.07) μg·L-1, respectively; tmax were (0.70±0.45) , (0.50±0.32) ,(0.50± 0.34) h, respectively; t1/2z were (2.78± 1.72) ,(5.29± 2.67) ,(5.31± 2.82) h, respectively. Conclusion The main pharmacokinetic parameters of mangiferin polymorphs in plasma of rats are different, and mangiferin form Ⅴ has the hightest AUC(0-24 h) and Cmax.
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Dihydropyridine (DHP) calcium channel blockers drugs (dipine in drug names) are currently used in the treatment of hypertension clinically. In recent years, with the emergence of generic drugs, it has been found that the drug efficacy is quite different from that of the original drug, and the reason is closely related to the difference in the crystal forms of the oral preparations. This paper reviews the polymorphic phenomenon of some DHP calcium channel blockers in the domestic market, introduces the clinical application and research progress of the DHP drugs, analyzes the differences between different crystal forms of the same drugs. This work may provide references and ideas for the research and development of generic drugs or new crystalline drug of DHP drugs.
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The purpose of this study was to investigate the effects of salvianolic acid A (SAA) in systemic lupus erythematosus (SLE) induced by pristane in BALB/c mice. Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane. Mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls. The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. Western blot analysis of renal tissue was also employed. SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects. SAA treatment also significantly inhibited the phosphorylation of IKK, IB and NFB in renal tissues of lupus mice. In conclusion, the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK, IB and NFB.
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Pulmonary artery hypertension is a disease with complicated pathogenesis, which is characterized by enhanced pulmonary artery constriction and arterial wall remodeling, leading to progressive increase of pulmonary vascular resistance and pulmonary artery pressure, then resulting in right heart failure.Many studies have shown that transforming growth factor-β1(TGF-β1) plays an important role in the development of various diseases, especially in cardiovascular and cerebrovascular diseases.TGF-β1 is involved in multiple cellular responses including cell proliferation, differentiation, migration and apoptosis.TGF-β1 participates in pulmonary artery hypertension mainly via promoting the proliferation of pulmonary artery smooth muscle cells as well as inducing the deposition of extracellular matrix and endothelial-to-mesenchymal transition(EndMT) through many signaling, which is mainly dominated by pulmonary artery smooth muscle cells and pulmonary artery endothelial cells.This review mainly introduces the role of TGF-β1 in pulmonary artery hypertension in order to provide potential drug targets and therapeutic strategies for pulmonary artery hypertension.
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Mangiferin also called Chinonin or mango, is mainly extracted from the Anacardiaceae and Gentianaceae plants. As polyphenol compounds, Mangiferin shows a strong antioxidant activity and a variety of pharmacological effects. In recent years, laboratory study has identified a variety of pharmacological effects associated with Mangiferin including preventing diabetes and its complications, regulating lipid metabolism abnormalities, antitumor, cardiovascular protection,anti hyperuricemia, neuro-protection, anti oxidation, anti-inflammation, antipyresis and analgesia, anti-bacteria and antivirus, antiradiation, liver pro-tection, promoting skeletal growth, anti allergy and immune reg-ulation,etc. In this paper, the research progress of pharmacolog-ical effects of Mangiferin is reviewed, analyzed and summarized in order to provide reference for further research and develop-ment.
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Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.
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OBJECTIVE To evaluate the effect of single traditional Chinese medicine(TCM) herb extracts on hepatoma and normal fibroblast cells using high-throughput screening in order to obtain extracts with specific anti-hepatoma effect. METHODS 242 commonly used TCM herbs were extracted by petroleum ether,ethanol and water,respectively. The total number of TCM extracts was 554. The cyto?toxicity of samples was evaluated by MTT in human hepatoma cells Bel7402 and mice normal fibroblasts NIH3T3. RESULTS 7.4%of the total extracts had an inhibitory effect greater than 50%for Bel7402,but 14.8% for fibroblasts NIH3T3 cells. Extracts with an inhibitory effect above 50% on both Bel7402 and NIH3T3 cells accounted for 4.4%of the total extracts. Our results showed that the sample DF173 had preferable cytotoxicity effect on hepatoma carcinoma cells in a good dose-effect relationship. DF173 is an ethanol extract from Stephania tetrandra,which is a commonly used herb in TCM. The cytotoxic IC50 of DF173 against Bel7402 was 8.27 mg·L-1,and 19.48 mg·L-1 on NIH3T3. CONCLUSION The components of TCM herbs are highly complicated. The combination of tumor cells with normal fibroblast cells to evaluate the cytotoxicity effect during anti-tumor drug screening will contribute much to the discovery of TCM drugs with high anti-tumor efficiency and lower toxicity.
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Aim To investigate the effect of Salvianol-ic acid A (Sal A)on mice with isoproterenol (ISO)-induced myocardial infraction and its possible mecha-nisms.Methods The mice were subcutaneously in-jected with ISO (8 mg·kg-1 )to induce myocardial in-farction.The myocardial protective effect of Salvianolic acid A was evaluated from mortality rate,electrocardio-gram (ECG),heart function,myocardial infarction in-dex,serum myocardial enzymes and its action mecha-nisms were explored from inflammation,anti-oxidation and cells apoptosis.Results Salvianolic acid A dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardi-al protection effects.ELISA results showed that Salvi- anolic acid A could reduce the expression of myocardial inflammatory cytokines such as IL-6(interleukin-6,IL-6),TNF-α(tumornecrosis factor-α,TNF-α).West-ern-blotting confirmed that Salvianolic acid A could in-crease the expression of anti-apoptotic proteins Bcl-2, reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.Con-clusion Salvianolic acid A displays a significant pro-tective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to the in-crease of PI3K/Akt signal pathway and the inhibition of cell apoptosis and inflammatory reaction.
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Aim To explore the therapeutical effect and mechanism of baicalein on two 6-hydroxydopamine (6-OHDA ) induced Parkinson′s disease (PD ) rat models,which received unilateral lesions of the left medial forebrain bundle (MFB ) or caudate putamen (CPu ) made by stereotaxic injection of 6-OHDA (MFB-M,CPu-M).Methods PD rat models were established by microinjection of 6-OHDA into MFB or CPu.The anti-tremor effect of baicalein on PD rat models was examined.Spontaneous activity was recor-ded. Dopamine (DA ), dihydroxyphenylacetic acid (DOPAC)and homovanilic acid (HVA)in striatum were quantified by HPLC-ECD.The tyrosine hydroxy-lase (TH)and OX-42 positive cells were detected by immunohistochemical method.The morphological vari-ation of the neurons was confirmed by analysis at an ul-trastructural level.Results Baicalein significantly in-creased the spontaneous activity in CPu-M.The elec-tromyography (EMG ) recordings revealed that com-pared with 6-OHDA group,the tremor frequency in ba-icalein group was decreased by 55% in MFB-M,and by 60% in CPu-M.6-OHDA treatment decreased DA levels in the striatum,while treatment with baicalein attenuated the DA decreases in CPu-M.Moreover,ba-icalein treatment could increase TH-positive neurons and decrease OX-42-postive microglia compared with 6-OHDA group in both MFB-M and CPu-M.Conclu-sions In the present study,it is illustrated that ①microinjection of 6-OHDA into the MFB and the CPu could cause different pathological changes of PD, which is important for efficacy evaluation;②baicalein showed the ability to alleviate the behavior symptoms in PD-rats at different stages by improving motor function and attenuating muscle tremor;③therapeutic effect of baicalein was produced by inhibiting the inflammatory medium production and release,anti-apoptosis,chan-ging dopamine catabolism, and inhibiting dopamine turnover.
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Objective To study the therapeutic effect of the complex mixture of luteolin and rutin ( MLR) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin ( MPTP) induced Parkinson’ s disease ( PD) mouse model. Methods Seventy-two C57BL/6 mice were divided into six groups randomly ( n=12 in each group): the normal control , model control , madopar (50 mg·kg-1) group, MLR at low (140 mg·kg-1), middle (280 mg·kg-1) and high (560 mg·kg-1) dose groups. PD mouse models were established by intraperitoneal injection of MPTP ( 30 mg · kg-1 ) . Pole test and traction performance were recorded to access the body coordinate capability and strength. The tyrosine hydroxylase (TH), dopamine transport protein ( DAT) , and glial fibrillary acidic protein ( GFAP ) positive cells were detected by immunohistochemical method. Dopamine ( DA ) , dihydroxyphenylacetic acid ( DOPAC ) , homovanilic acid ( HVA ) , 5-hydroxytryptamine ( 5-HT ) and 5-hydroxyindoleacetic acid (5-HIAA) in striatum were quantified by HPLC-ECD. Results MLR significantly ameliorated mouse motor coordination ability (P<0. 01 or P<0. 05). MLR at 280 and 560 mg·kg-1 could increase TH-positive neurons by 69. 00%and 77. 95% compared with the normal control group (P<0. 01) and DAT-positive neurons by 68. 53% and 70. 40% compared with the normal control group(P<0. 05), and decrease GFAP-postive astrocyte reactivity. The treatment with MLR at three doses attenuated the monoamine neurotransmitter disorder. Conclusion MLR markedly improves MPTP caused movement coordinate ability injury in mice and exerts therapeutic action on PD by regulating neurotransmitters in brain, inhibiting the inflammatory reaction and alleviating the neuron injury.
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Salvia miltiorrhiza is dry root or rhizome of the labia-tae plant Salvia miltiorrhiza, whose water-soluble ingredients are recognized as its bioactive components in cardiovascular disea-ses. Based on researches at home and abroad in recent years, this article summarizes pharmacological effect resisting myocardi-al ischemia of Salvia miltiorrhiza ’ s water soluble compounds in multi-level from the prevention, treatment and anti-reperfusion damage, to provide theoretical basis for the research and devel-opment of the active monomers in Salvia miltiorrhiza and com-pound preparations.
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Abstrcat:Pulmonary artery hypertension ( PAH) is a cardiopul-monary disease with extensive obliterative changes in the small to midsized pulmonary arterioles. This review summarizes the al-tered inflammation and immune processes underlying the devel-opment of PAH, and discusses inflammatory factors, immune cells, Rho kinase and gene implicated in PAH. Preclinical stud-ies have provided the basis for abnormal immune response in ani-mal models of the PAH, and this paper, based on inflammatory/immune response mechanisms, proposes PAH potential therapeu-tic targets.
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Systemic lupus erythematosus ( SLE) is a chronic multisystem relapsing-remitting autoimmune disease, which affects human health seriously.There are numerous animal models that have long been employed in an effort to un-derstand the mechanism and treatment of SLE.Animal models of SLE were reviewed and compared in this paper, to provide references for the researchers to choose appropriate models for studying specific pathogenic mechanism and diagnostic crite-ria, searching for targeted treatment interventions and developing potential therapeutic drugs.
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RhoA belongs to the small G binding proteins Rho subfamily, playing an important role in the various cellular func-tions, including migration, proliferation, adhesion and apopto-sis. Recent data indicate that RhoA/ROCK pathway causes myo-cardial damage by influencing the myocardial energy metabolism, inflammation, and endoplasmic reticulum stress. On the other hand, the activation of RhoA also has a positive role in MIRI. This article reviews the regulatory effect of RhoA on MIRI and its mechanisms, discusses the prospects of RhoA as a novel thera-peutic target for MIRI, and provides new therapeutic treatments and strategies for MIRI.
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Vascular calcification is a process similar to bone de-velopment, which is excessively abnormal deposition of calcium and phosphate in blood vessel wall. It is a sign of early athero-sclerosis formation, and can reduce the atherosclerotic vascular compliance. The common regulation of vascular calcification is affected by many factors. This article discusses the formation of vascular calcification from the molecular mechanism, the chemi- ＜br> cal mechanism and metabolic factors. It also reviews the progress of the prevention of vascular calcification by traditional Chinese medicine.
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Aim ToestablishthemethodofHighper-formance liquid chromatography ( HPLC ) for detecting plasma concentration of indazole compound DL0805-1 , a Rho kinase inhibitor, and to investigate its pharma-cokinetics in rats with intravenous injection. Methods ThedetectingsystemwasAgilent1200-DAD;chro-matographic column was Agilent TC-C18 ( 4. 6 mm × 250 mm, 5 μm); the ultraviolet detection wavelength was 235 nm; the column temperature was 35 ℃; the flow rate was 1 ml·min-1;the mobile phase was ace-tonitrile-0. 05% H3 PO4 gradient elute. Rat blood sam-ples were collected at different intervals after intrave-nous injection of a single dose of DL0805-1 , and the concentration of DL0805-1 in rat plasma were deter-mined by HPLC method for estimating pharmacokinetic parameters.Results Afterintravenousinjectionof DL0805-1 in rats, prototype and its metabolite were detected in plasma. T1/2 of DL0805-1=(2. 34 ± 1. 42) h, Cmax=(3. 51 ± 0. 44) mg·L-1, T1/2 of metabolite of DL0805-1 = ( 1. 27 ± 0. 45 ) h, Cmax = ( 3. 55 ± 0.22)mg·L-1.Conclusion Theseresultssuggest that DL0805-1 may be metabolized into another sub-stance in vivo and play biological functions. The meth-od is sensitive, simple, and accurate, and can be used for the determination of DL0805-1 in rat plasma and pharmacokinetic studies.
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Aim To investigate the in vitro vasorelax-ant effect of DL0805-0, a Rho kinase inhibitor, on iso-lated rat thoracic aorta and explore its underlying mechanism. Methods Tension was measured to eval-uate the vasorelaxant effect of DL0805-0 on rat endo-thelium-intact and endothelium-denuded thoracic aorta rings. Rho kinase inhibitor fasudil, nitric oxide syn-thase inhibitor Nω-nitro-L-arginine methyl ester ( L-NAME), guanylate cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin, calcium-activa-ted potassium channel blocker tetraethyl ammonium ( TEA ) , ATP-sensitive potassium channel blocker glibenclamide and voltage-dependent potassium chan-nel blocker 4-aminopyridine ( 4-AP ) were used to il-lustrate the mechanisms of vasorelaxant effect of DL0805-0 . Results DL0805-0 exerted vasorelaxation in a dose-dependent manner in KCl (60 mmol·L-1 ) or NE ( 0. 1 μmol · L-1 ) -induced contraction. DL0805-0-induced vasorelaxation was significantly re-duced by L-NAME. However, methylene blue and in-domethacin did not significantly affect vasorelaxation of DL0805-0. In endothelium-denuded rings, TEA re-markably attenuated the vasorelaxant effect of DL0805-0 , while glibenclamide and 4-AP did not affect vasore laxation of DL0805-0 significantly. DL0805-0 also re-duced NE-induced transient contraction and inhibited contraction induced by increasing extracellular calci-um. Conclusion These results suggest that DL0805-0 induces vasorelaxation through an endothelium-depend-ent pathway. The opening of calcium-activated K+channels and blocking of Ca2+ channels in vascular smooth muscle cells may be one of the mechanisms of DL0805-0-induced vasorelaxation.
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Myocardial ischemic preconditioning and postconditioning can reduce myocardial infarct size, improve myocardial contractility, protect coronary endothelial and myocardial cell ultrastructure, as well as reduce the incidence of arrhythmias. Clinical practice has confirmed the safety and efficacy of these two methods of myocardial protection. This paper reviewed about ischemic preconditioning and postconditioning protection mechanisms in myocardial ischemia reperfusion injury and clinical research literatures in recent years, to provide a theoretical basis for finding new treatment strategies on the prevention and treatment of ischemic cardiomyopathy.
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Salvianolic acid A is a water-soluble component from Danshen, which is frequently used in traditional Chinese medicine. High performance liquid chromatography was often used to analyze content of salvianolic acid A. The yield of salvianolic acid A increased by the technological improvement of extraction and separation. Salvianolic acid A possessed multiple pharmacological activities, including antioxidants, myocardial ischemic protection, antithrombatic, neuroprotection, anti fibrosis, prevention of diabetes and complications. Recently, preliminary pharmacokinetics characteristics of salvianolic acid A were clarified. Based on the research literature and study work from author's laboratory, this review will focus on recent developments concerning the chemistry, pharmacology and pharmacokinetic of salvianolic acid A, and prospect further research.