Search

This study investigated the effects of methanol extract Magnolia officinalis (MEMO) on baroreceptor reflex sensitivity (BRS) in the hypercholesterolemic rabbits and the involved molecular mechanisms. Male New Zealand white rabbits were randomly divided into Control (normal diet), Cholesterol (0.5% w/w cholesterol diet), and Magnolia groups (0.5% w/w cholesterol diet plus 1% w/w MEMO). The animals were treated with the designated diet for 4 or 8 weeks. BRS in the control of heart rate was assessed by linear regression method. After 8 weeks of treatments, plasma total cholesterol (TC) was significantly elevated in the Cholesterol/Magnolia groups. The arterial blood pressure (aBP) was increased in the Cholesterol and Magnolia groups. The depression of BRS observed in the Cholesterol group was significantly ameliorated in the Magnolia group. After L‐NAME (Nω‐nitro‐Larginine methyl ester, 20 mg/kg, iv), the BRS of the Cholesterol group was significantly improved. Results from our in vitro study further indicated that honokiol, the principle component of MEMO, would protect human umbilical vein endothelial cells (HUVECs) from H2O2‐induced damages and inhibit H2O2‐induced vascular smooth muscles cells (VSMCs) proliferation, which was evident by the decreased expression of pFAK, and p‐Erk1/2. The results of the present study suggested that the improvement of BRS by MEMO in the hypercholesterolemic rabbits might be mediated by the antioxidant property of MEMO as indicated by the results from the L‐NAME and in vitro honokiol studies.

The aim of this study was to assess a possible correlation between zolpidem use and acute pyelonephritis (APN) in women in Taiwan. Therefore, we performed a case-control study involving the Taiwan's National Health Insurance Research Database between 2000 and 2011. This study included 3151 female participants aged 20 to 84 years who experienced the first bout of APN (case group) and 6015 randomly selected female participants without APN (control group). Zolpidem use was defined as "current," "early," or "late," if the last remaining 1 tablet for zolpidem was detected within 7 days, between 8 and 14 days, or ≥15 days before the date of APN diagnosis, respectively. The multivariable unconditional logistic regression model was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the correlation between zolpidem use and APN. After adjusting for confounders, the multivariable analysis yielded an adjusted APN OR of 2.2 for participants with current zolpidem use (95%CI 1.7-2.8) compared with participants who never used zolpidem. The adjusted ORs gradually decreased to 1.4 for participants with early zolpidem use (95%CI 0.8-2.5) and 1.1 for participants with late zolpidem use (95%CI 0.9-1.2), but without statistical significance. Only patients with current zolpidem use had a significantly increased relative risk of APN. Additional large confirmatory studies are needed to illustrate a causal relationship. Meanwhile, physicians and pharmacists should be more cautious about the risk of APN when prescribing and dispensing zolpidem in women.

cope Curcumin has been shown to affect platelet-derived growth factor (PDGF)- and tumor necrosis factor (TNF)-α-elicited vascular smooth muscle cell (VSMC) migration and inhibit neointima formation following vascular injury. However, whether two other curcuminoids isolated from Curcuma longa, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), also demonstrate antimigratory activity in VSMCs similar to that of curcumin remain uncharacterized. Methods and results Based on 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and proliferating cell nuclear antigen immunostaining analyses as well as changes in intima/media ratios, we show that DMC exhibits more potent effects than the other curcuminoids. We aimed to evaluate the effects and characterize the molecular mechanisms of DMC on VSMC migration and neointima formation in a carotid injury model. DMC decreased the expression of matrix metalloproteinase 2/9 and inhibited VSMC migration as demonstrated by in vitro scratch wound and transwell assays. Furthermore, DMC may inhibit the migration of VSMCs by reducing the expression of matrix metalloproteinase 2/9 via downregulation of the focal adhesion kinase/phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) and phosphoglycerate kinase 1/extracellular signal regulated kinase 1/2 signaling pathways. Using a rat carotid arterial injury model, we show that DMC treatment was more potent than treatment with the other curcuminoids with respect to reducing intima/media ratios and the number of proliferating cells. Conclusion DMC should be considered for therapeutic use in preventing VSMC migration and attenuating restenosis following balloon-mediated vascular injury.

1. The aim of the present study was to investigate the molecular mechanisms by which pipoxolan exerts its inhibitory effects and apoptotic activity in human leukaemia HL-60 cells. 2. The effects of pipoxolan on the proliferation of HL-60 cells and on the distribution of cells within different phases of the cell cycle were investigated indirectly using a Trypan blue assay and a flow cytometer, respectively. The effects of pipoxolan on the apoptosis of HL-60 cells was investigated using DNA fragmentation and flow cytometer. The expression of factors affecting the cell cycle and apoptosis, including p53, p21, Bax, Bcl2, cytochrome c, caspase 3 and caspase 9, was examined by western blotting. 3. At 6.25 microg/mL, pipoxolan significantly induced apoptosis in human leukaemia HL-60 cells after 24 h exposure. In addition, HL-60 cells were arrested in the G(0)/G(1) phase via the induction of p53/p21 by pipoxolan. Apoptosis was associated with an increased Bax/Bcl-2 ratio, cytochrome c release, cleavage of procaspases-9 and -3 and hydrolysis of poly(ADP-ribose) polymerase. Intracellular reactive oxygen species (ROS) seem to play a key role in the pipoxolan-induced apoptosis, because high levels of ROS were produced early in the drug treatment. Apoptosis was significantly abrogated by the free radical scavenger N-acetylcysteine (NAC).

BACKGROUND: Plant invertases play important roles in sucrose metabolism. Cell wall invertase has been reported to participate in phloem loading and unloading. Soluble invertases are involved in hexose level regulation in mature tissues and in utilisation of stored sucrose within vacuoles. Invertase inhibitory proteins have been described as one of the possible components for invertase activity regulation in some plant species. RESULTS: In this work an invertase inhibitor (ITI) coding sequence was cloned by differential display from sweet potato (SP) storage roots. SPITI codes for a protein of 192 amino acids with a predicted molecular mass of 20 624 Da containing a 20-amino-acid signal peptide and four cysteines. Computer analysis of the deduced amino acid sequences of the conserved domain revealed that the protein belonged to the plant invertase/pectin methylesterase inhibitor. Both the corresponding mRNA and protein levels were found to be highest in storage roots, followed by veins. Recombinant SPITI protein from the storage root cDNA clone overproduced in Escherichia coli (M15) was purified by affinity chromatography. This protein effectively inhibited the invertase activity in a dose-dependent manner. The results presented in the Lineweaver-Burk plots indicated that the invertase inhibitor displayed a mode of competitive inhibition towards the invertase tested, with a Ki of 3.82 × 10−6 mol L−1. CONCLUSION: These results suggested that SPITI is a novel member of the ITI family in plants. SPITI genes of sweet potato storage roots display differential gene expression patterns, which may be associated with sucrose metabolism to cope with particular developmental requirements. Copyright © 2008 Society of Chemical Industry

BACKGROUND: Several inflammatory diseases are thought to be related to oxidative injury and reactive oxygen species have been proposed as important causative agents of heart disease and ageing. This study was designed to investigate the effects of sweet potato trypsin inhibitor (SPTI) on antioxidant enzymes, lipid peroxidation and lipid profiles in mice. RESULTS: Twenty mice were randomly divided into four groups and fed with TI (10, 50 and 100 mg kg−1 BW) as treatment and with saline as a control in addition to regular diets. After 35 days, Trolox equivalent antioxidant capacity (TEAC), triglyceride (TG) and cholesterol levels in plasma and superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS) in liver were measured. Serum from the group that had received the the highest oral dose of SPTI (100 mg kg−1 BW) had the highest total antioxidant activity (expressed as 3.59 ± 0.237 mmol L−1 TEAC). The SOD, catalase and GPx activity of SPTI groups were significantly increased compared with the control group. Malondialdehyde (MDA) was significantly lower in all experimental groups compared with the control one. No significant differences in the concentration of low-density lipoprotein (LDL)-cholesterol was found, but high density lipoprotein (HDL)-cholesterol, triglyceride (TG) and total cholesterol tended to decrease. CONCLUSION: This study showed that the oral intake of SPTI in mice may trigger inflammatory responses which result in an increase in antioxidant enzyme activities, and a decrease in MDA, TG and total cholesterol, which are known risk factors of inflammatory and heart disease. Copyright © 2008 Society of Chemical Industry

We performed ab initio electronic structure calculations on the structures and energetics of the mixed hyperalkaliated hydrogen oxides Li4OH, Li3NaOH, and Li2Na2OH. Five equilibrium geometries exist for each complex of Li4OH and Li3NaOH, and seven minima were located for Li2Na2OH. The calculated dissociation energies for the possible dissociation pathways are all endothermic. The global minimum structures of the three complexes have C2v symmetry and contain a hydrogen-bridged, Li−H−Li, three-centered skeleton. We also investigated the charge redistribution within these complexes in their ionic forms. The energetic factors governing the construction of the equilibrium structures and their bonding properties are analyzed.