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Background Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties. Purpose The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved. Study Design and Methods Hyperhomocysteinemia (HHcy) rat model was induced by feeding 3% methionine. A rat thoracic aortic ring model was used to investigate the effects of physcion on Hcy-induced impairment of endothelium-dependent relaxation. Two doses, low (L, 30 mg/kg/day) and high (H, 50 mg/kg/day) of physcion were used in the present study. To construct Hcy-injured human umbilical vein endothelial cells (HUVECs) model, the cells treated with 3 mM Hcy. The effects of physcion on Hcy-induced HUVECs cytotoxicity and apoptosis were studied using MTT and flow cytometry. Confocal analysis was used to determine the levels of intracellular Ca2+. The levels of protein expression of the apoptosis-related markers Bcl-2, Bax, caspase-9/3, and Akt and endothelial nitric oxide synthase (eNOS) were evaluated by western blot. Results In the HHcy rat model, plasma levels of Hcy and malondialdehyde (MDA) were elevated (20.45 ± 2.42 vs. 4.67 ± 1.94 μM, 9.42 ± 0.48 vs. 3.47 ± 0.59 nM, p Conclusion Physcion prevents Hcy-induced endothelial dysfunction by activating Ca2+- and Akt-eNOS-NO signaling pathways. This study provides the first evidence that physcion might be a candidate agent for the prevention of cardiovascular disease induced by Hcy.

Homocysteine (Hcy) is an independent risk factor in the development of cardiovascular diseases (CVD). Hyperhomocysteinemia (HHcy), induces the injury of vascular endothelial cells via oxidative stress. Oxymatrine (OMT), one of the main components of Sophora flavescens, has displayed anti-inflammatory, anti-oxidant and anti-apoptotic activity. However, the effect of OMT on the Hcy-induced endothelial injury is not clearly defined yet. The aim of this study was to determine the protective effect of OMT on the Hcy-induced endothelial injury and its mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro. Methyl thiazolyl tetrazolium assay (MTT), fluorescence staining, flow cytometry and western blotting were used in this study. OMT prevented the Hcy-induced toxicity and apoptosis in HUVECs. Moreover, OMT suppressed Hcy-induced increases in reactive oxygen species, lactate dehydrogenase, malondialdehyde levels and increased superoxide dismutase levels. OMT reversed the Hcy-induced decrease in the protein expression of nuclear factor erythroid-2-related factor 2 (Nrf2). In addition, OMT reversed the Hcy-induced apoptosis related biochemical changes such as decreased mitochondrial membrane potential and Bcl-2/Bax protein ratio, and increased protein expression of caspase-9 and caspase-3. Furthermore, OMT elevated the phosphorylation levels of Akt and eNOS, and the formation of nitric oxide (NO) in injured cells. These results suggest that OMT prevents Hcy-induced endothelial injury by regulating mitochondrial-dependent apoptosis and Akt-eNOS-NO signaling pathways concomitantly with accentuation of Nrf2 expression.

Ethnopharmacological relevance Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined. Aim of the study The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings. Materials and methods Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta. Results EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with N G -nitro- l -arginine methylester ( l -NAME) or 1 H -[1,2,4]-oxadiazolo-[4,3- α ]-quinoxalin-1-one (ODQ). Extracellular Ca 2+ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca 2+ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd 3+ , and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective K Ca channels blocker, or glibenclamide, an ATP-sensitive K + channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation. Conclusions The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both K Ca and K ATP channels and inhibition of L-type Ca 2+ channels.

Aim of the study The aim of the present study was to define the effect of Xanthoceras sorbifolia extracts (XS) on vascular tension and responsible mechanisms in rat thoracic aortic rings. Materials and methods Ethanol extract of the leaves of XS (EXS) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta. Results EXS (0.1–100 μg/ml) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished EXS-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N G -nitro- l -arginine methylester ( l -NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited EXS-induced vasorelaxation. Inhibition of Ca 2+ entry via l -type Ca 2+ channels failed to block the EXS-induced vasorelaxation. Extracellular Ca 2+ depletion significantly attenuated EXS-induced vasorelaxation. Modulators of the store-operated Ca 2+ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate (2-APB) and Gd 3+ , and an inhibitor of Akt, wortmannin, markedly attenuated the EXS-induced vasorelaxation. EXS increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by l -NAME, ODQ, thapsigargin, Gd 3+ , 2-APB, and wortmannin. Further, EXS-induced vasorelaxation was significantly attenuated by tetraethylammonium, a non-selective K ca channels blocker, but not by glibenclamide, an ATP-sensitive K + channels inhibitor. Inhibition of cyclooxygenase with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on EXS-induced vasorelaxation. Conclusions The present study suggests that EXS relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt- and SOCE-eNOS-sGC pathways, which may, at least in part, be related to the function of K + channels.

The genetic diversity of 279 indivdiuals from 10 populations in Shandong Province was investigated using inter-simple sequence repeat (ISSR) markers. As a result, 116 bands were amplified by 10 informative and reliable primers, of which 101 were polymorphic loci. A relatively high level of genetic diversity was revealed: PPL = 87.07, He = 0.2697, H0 = 0.3999 (at the species level); PPL = 64.58, He = 0.2004, H0 = 0.3010 (at the population level). A higher level of genetic differentiation was detected among populations with Nei's G(ST) analysis and the analysis of molecular variance (AMOVA; G(ST) = 0.2414, F(ST) = 0.2224). Habitat fragmentation and gene flow may result in genetic differentiation. UPGMA cluster analysis indicated that the four populations from Linshu, Junan, Tancheng and Feixian grouped together, whereas Laiyang populations clustered in an isolated clade. The results showed that a mixed mating system was possibly the main factor influencing the genetic structure of this species. These results, combined with other information about Castanea mollissima, may provide a valuable basis for proposing conservation strategies.

This study was carried out to investigate the influence of medium composition for in vitro mass propagation of Lycoris squamigera Max. After the disks of short stems, segments of leaf within bulb and scale were cultured on MS basal medium supplemented with various plant growth regulators, they were examined for the extent of callus formation, shoot and root regeneration. In the culture of stem disks, adventitious shoots were regenerated from the basal tissue of bulb scales, and combined medium of 1.0 mg/L 2,4-D or NAA＋2.0 mg/L BA or kinetin showed the the best response and 4∼6 shoots per explant formed. In the culture of leaf segments within bulbs, both MS medium supplemented with 1.0 mg/L NAA＋2.0 mg/L TDZ and with 1.0 mg/L 2,4-D＋1.0∼2.0 mg/L BA were produced callus profusely on the base of leaf tissue and 3∼6 shoots were regenerated per explant. In the scale segments culture, calli were produced on the basal tissue on medium with 1.0 mg/L 2,4-D＋1.0∼2.0 mg/L BA. The best result were shown on MS medium with 1.0 mg/L NAA＋2.0 mg/L TDZ, and 1.0 mg/L 2,4-D＋1.0∼2.0 mg/L BA. Maximum number of regenerated shoots was up to 10∼12. Adventitious root formation from explants were formed profusely on MS medium with 1.0 mg/L NAA＋2.0 mg/L kinetin. The most desirable method for mass propagation of plantlets was the shoot regeneration from scale segments then subsequently subcultured on medium for rooting.

Mesangial cell proliferation is correlated with the progression of renal failure. The purpose of this study was to determine whether a water extract of Poria cocos Wolf (WPC), a well-known medicinal plant, regulates rat mesangial cell proliferation in the presence of high glucose (HG). HG significantly accelerated [3H]-thymidine incorporation, which was inhibited by WPC (1–50 μg/mL) in a dose-dependent manner. Cell migration and fibronectin mRNA expression data also supported the anti-proliferative effect of WPC. Western blot analysis revealed that pretreatment with WPC decreased the expression of cyclins and cyclin-dependent kinases (CDKs) and promoted the expression of p21waf1/cip1and p27kip1. WPC also suppressed HG-induced p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. Furthermore, WPC inhibited HG-induced production of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). In conclusion, HG promoted mesangial cell proliferation, and WPC inhibited this activity, at least in part, via induction of cell cycle arrest and activation of anti-oxidant properties. Taken together, these results suggest that P. cocos may be a potent regulator of HG-induced proliferation.