bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a three‐dimensional culture model of prostatic epithelial cells and its use for the study of epithelial‐mesenchymal transition and inhibition of PI3K pathway in prostate cancer
Authors: Chu Jian Hong , Yu Shan , Hayward Simon W. , Chan Franky L.
Published: December 2008

BACKGROUND

Appropriate 3D culture models of human prostatic epithelial cells resembling normal growth pattern and architecture of prostate gland and its malignant development are scarce.

METHODS

Here, we optimized the 3D culture conditions of the immortalized non‐transformed human prostatic epithelial cell line BPH‐1 in Matrigel and developed a 3D culture model closely mimicking prostatic glandular structure.

RESULTS

Our results showed that BPH‐1 cells cultured in Matrigel formed acinus‐like spheroids with lumen formation and polarized differentiation. To establish an androgen‐stimulated differentiation in AR‐negative BPH‐1, we generated AR‐transduced BPH‐1 cells, which displayed androgen‐induced secretory differentiation and growth suppression in 3D culture. We also evaluated the spheroid forming capacity of tumorigenic derivative BPH‐1CAFTD sublines in 3D culture and their responses to PI3K inhibitor LY294002. Results showed that these tumorigenic BPH‐1CAFTD sublines did not exhibit polarized differentiation in Matrigel culture. Interestingly, polarization could be restored by LY294002 treatment of BPH‐1CAFTD1 but not of BPH‐1CAFTD3 subline. Finally, we employed this 3D culture model to examine the significance of an EMT‐regulatory transcription factor Snail in prostate cancer development by its stable transduction into BPH‐1 cells. Results showed that BPH‐1‐Snail cells lost their spheroid forming capacity and exhibited an invasive phenotype.

CONCLUSIONS

Taken together, we established a 3D culture model of human prostatic epithelial cells with structural and functional relevance to normal prostate gland and prostate cancer development and also demonstrated that this 3D model might be useful to assess the ability of drugs to restore differentiation as a potential surrogate measure of efficacy for prostate cancer therapy. Prostate 69:428–442, 2009. © 2008 Wiley‐Liss, Inc.
Differential involvement of reactive oxygen species and nucleoside transporters in cytotoxicity induced by two adenosine analogues in human prostate cancer cells
Authors: Minelli Alba , Bellezza Ilaria , Tucci Arianna , Rambotti Maria Grazia , Conte Carmela , Culig Zoran
Published: December 2008

BACKGROUND

Elevated levels of cellular oxidative stress represent a specific vulnerability of malignant cells and exposure to cytotoxic drugs is known to induce oxidative stress in cancer cells. The effects of two adenosine analogues, 2‐chloroadenosine and 2‐chlorodeoxyadenosine, were investigated to assess their mechanism of action in prostate cancer cells.

METHODS

Androgen‐independent and ‐sensitive (PC3 and LNCaP) prostate cancer cells and mouse primary prostate cultures were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2‐chloroadenosine and 2‐chlorodeoxyadenosine. Adenosine receptors and nucleoside transporters expression were determined by RT‐PCR. GSH and reactive oxygen species levels were determined by DTNB and DCFH‐DA, respectively. Nuclear translocation of Nrf2 was assessed by Western blotting.

RESULTS

2‐Chloroadenosine marginally affected primary prostate cells viability whereas it was more potent than 2‐chlorodeoxyadenosine in reducing viability and increasing apoptosis in both prostate cancer cell lines. Moreover, ROS levels and GSH content were markedly affected in PC3 whereas only ROS production was increased in LNCaP cells. The antioxidant butylated hydroxytoluene protected PC3 cells from GSH depletion and reduction in cell viability induced by 2‐chloroadenosine.

CONCLUSIONS

2‐Chloroadenosine, but not 2‐chlorodeoxyadenosine is capable of inducing apoptosis in prostate cancer cells, an effect which may be explained at least partially by the capacity of the nucleoside analogue to modify ROS and GSH levels. These observations may offer a rationale for the use of 2‐chloroadenosine to improve the clinical efficacy of GSH‐dependent antitumor drugs. Prostate 69:538–547, 2009. © 2008 Wiley‐Liss, Inc.
Expression of androgen and estrogen related proteins in normal weight and obese prostate cancer patients
Authors: Gross Mitchell , Ramirez Cristina , Luthringer Daniel , Nepomuceno Edward , Vollmer Robin , Burchette James , Freedland Stephen J.
Published: December 2008

BACKGROUND

Obesity is associated with an aggressive form of prostate cancer and with alterations in androgen and estrogen metabolism. We hypothesized that changes in components of the sex steroid receptor axis may contribute to the clinical aggressiveness of prostate cancer in obese patients.

METHODS

A database was assembled containing clinical and pathological variables from 539 patients treated with radical prostatectomy at a single urban hospital between 1994 and 2002. Tissue microarrays were constructed from representative patients and expression of androgen receptor (AR), PSA, estrogen receptor α (ERα), estrogen receptor β (ERβ), and aromatase was examined.

RESULTS

Higher BMI correlated strongly with black race, the presence of extra‐capsular extension, and higher pathologic stage. Expression of AR, PSA, ERβ and aromatase in cancerous epithelial cells did not differ according to obesity status. However, decreased expression of ERα and aromatase was observed in the stromal compartment surrounding non‐cancerous acini in obese patients.

CONCLUSION

We confirm the previously reported associations between obesity and aggressive clinical and pathologic features in our single‐institution, urban teaching hospital. In comparing obese versus non‐obese patients, there was no difference in expression of androgen or estrogen related proteins in cancerous epithelial cells. However, there was a down‐regulation of ERα and aromatase in the stroma of obese patients. Our data suggest obesity may cause stromal changes in the sex steroid production and signaling pathways which may affect prostate cancer growth via intracrine/paracrine mechanisms. Prostate 69:520–527, 2009. © 2008 Wiley‐Liss, Inc.
Conformational dynamics of the EGFR kinase domain reveals structural features involved in activation
Authors: Papakyriakou Athanasios , Vourloumis Dionisios , Tzortzatou‐Stathopoulou Fotini , Karpusas Michael
Published: December 2008

The epidermal growth factor receptor (EGFR) has been the focus of intensive studies because of its importance in cancer research. Thus, a broader understanding of the molecular mechanism of activation of the EGFR kinase will have profound significance for the development of novel therapeutics. Numerous crystal structures of EGFR kinase, including the structure of the activating‐kinase dimer, have provided snapshots of the specific pathway. Herein, we performed unrestrained‐, as well as targeted‐molecular dynamics simulations based on these data, to gain further insight into the conformational changes responsible for activation. Comparison of the monomer‐ versus activating‐EGFR‐dimer simulations indicates that the dimerization is stabilizing structural elements associated with the activated state and predicts new salt‐bridge interactions involving activation‐loop residues that may also be associated with that state. Targeted molecular dynamics simulations of the inactive‐to‐active EGFR transition, as well as the reverse pathway, confirm the formation of conserved structural features of functional importance for the activity or stabilization of either conformation. Interestingly, simulations of the L834R mutant, which is associated with cancer, suggest that the structural basis of the activation induced by that mutation might be the ability of the mutated R834 residue to consecutively form salt bridges with neighboring acidic residues and cause destabilization of a hydrophobic cluster in the inactive state. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations
Authors: Khelashvili George , Grossfield Alan , Feller Scott E. , Pitman Michael C. , Weinstein Harel
Published: December 2008

An unresolved question about GPCR function is the role of membrane components in receptor stability and activation. In particular, cholesterol is known to affect the function of membrane proteins, but the details of its effect on GPCRs are still elusive. Here, we describe how cholesterol modulates the behavior of the TM1‐TM2‐TM7‐helix 8(H8) functional network that comprises the highly conserved NPxxY(x)5,6F motif, through specific interactions with the receptor. The inferences are based on the analysis of microsecond length molecular dynamics (MD) simulations of rhodopsin in an explicit membrane environment. Three regions on the rhodopsin exhibit the highest cholesterol density throughout the trajectory: the extracellular end of TM7, a location resembling the high‐density sterol area from the electron microscopy data; the intracellular parts of TM1, TM2, and TM4, a region suggested as the cholesterol binding site in the recent X‐ray crystallography data on β2‐adrenergic GPCR; and the intracellular ends of TM2‐TM3, a location that was categorized as the high cholesterol density area in multiple independent 100 ns MD simulations of the same system. We found that cholesterol primarily affects specific local perturbations of the helical TM domains such as the kinks in TM1, TM2, and TM7. These local distortions, in turn, relate to rigid‐body motions of the TMs in the TM1‐TM2‐TM7‐H8 bundle. The specificity of the effects stems from the nonuniform distribution of cholesterol around the protein. Through correlation analysis we connect local effects of cholesterol on structural perturbations with a regulatory role of cholesterol in the structural rearrangements involved in GPCR function. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Folding simulations of Trp‐cage mini protein in explicit solvent using biasing potential replica‐exchange molecular dynamics simulations
Authors: Kannan Srinivasaraghavan , Zacharias Martin
Published: December 2008

Replica exchange molecular dynamics (RexMD) simulations are frequently used for studying structure formation and dynamics of peptides and proteins. A significant drawback of standard temperature RexMD is, however, the rapid increase of the replica number with increasing system size to cover a desired temperature range. A recently developed Hamiltonian RexMD method has been used to study folding of the Trp‐cage protein. It employs a biasing potential that lowers the backbone dihedral barriers and promotes peptide backbone transitions along the replica coordinate. In two independent applications of the biasing potential RexMD method including explicit solvent and starting from a completely unfolded structure the formation of near‐native conformations was observed after 30–40 ns simulation time. The conformation representing the most populated cluster at the final simulation stage had a backbone root mean square deviation of ∼1.3 Å from the experimental structure. This was achieved with a very modest number of five replicas making it well suited for peptide and protein folding and refinement studies including explicit solvent. In contrast, during five independent continuous 70 ns molecular dynamics simulations formation of collapsed states but no near native structure formation was observed. The simulations predict a largely collapsed state with a significant helical propensity for the helical domain of the Trp‐cage protein already in the unfolded state. Hydrogen bonded bridging water molecules were identified that could play an active role by stabilizing the arrangement of the helical domain with respect to the rest of the chain already in intermediate states of the protein. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Crystal structure of a novel Sm‐like protein of putative cyanophage origin at 2.60 Å resolution
Authors: Das Debanu , Kozbial Piotr , Axelrod Herbert L. , Miller Mitchell D. , McMullan Daniel , Krishna S. Sri , Abdubek Polat , Acosta Claire , Astakhova Tamara , Burra Prasad , Carlton Dennis , Chen Connie , Chiu Hsiu‐Ju , Clayton Thomas , Deller Marc C. , Duan Lian , Elias Ylva , Elsliger Marc‐André , Ernst Dustin , Farr Carol , Feuerhelm Julie , Grzechnik Anna , Grzechnik Slawomir K. , Hale Joanna , Han Gye Won , Jaroszewski Lukasz , Jin Kevin K. , Johnson Hope A. , Klock Heath E. , Knuth Mark W. , Kumar Abhinav , Marciano David , Morse Andrew T. , Murphy Kevin D. , Nigoghossian Edward , Nopakun Amanda , Okach Linda , Oommachen Silvya , Paulsen Jessica , Puckett Christina , Reyes Ron , Rife Christopher L. , Sefcovic Natasha , Sudek Sebastian , Tien Henry , Trame Christine , Trout Christina V. , van den Bedem Henry , Weekes Dana , White Aprilfawn , Xu Qingping , Hodgson Keith O. , Wooley John , Deacon Ashley M. , Godzik Adam , Lesley Scott A. , Wilson Ian A.
Published: December 2008

ECX21941 represents a very large family (over 600 members) of novel, ocean metagenome‐specific proteins identified by clustering of the dataset from the Global Ocean Sampling expedition. The crystal structure of ECX21941 reveals unexpected similarity to Sm/LSm proteins, which are important RNA‐binding proteins, despite no detectable sequence similarity. The ECX21941 protein assembles as a homopentamer in solution and in the crystal structure when expressed in Escherichia coli and represents the first pentameric structure for this Sm/LSm family of proteins, although the actual oligomeric form in vivo is currently not known. The genomic neighborhood analysis of ECX21941 and its homologs combined with sequence similarity searches suggest a cyanophage origin for this protein. The specific functions of members of this family are unknown, but our structure analysis of ECX21941 indicates nucleic acid‐binding capabilities and suggests a role in RNA and/or DNA processing. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Safely scale‐up processes and accommodate recipe changes
Authors: Theis Amy E. , Burelbach James P. , Askonas Charles F.
Published: December 2008

Thermal hazards screening can be quickly and cost‐effectively performed to obtain the required data for the safe scale‐up of chemical processes and to accommodate changes to process recipes. Before scale‐up, it is vital to identify safe temperature and pressure operating ranges, quantify the heat generated from a reaction, and the number of moles of gas generated. It is also prudent to determine the heat and gas generation rates to safely accommodate the reaction in the given process equipment. These rate data can also be used to verify the adequacy of the existing pressure relief system design. Process Hazard Analysis (PHA) and Hazard and Operability (HAZOP) reviews identify credible upset scenarios, and data are required to address these issues. When a process recipe or batch size is changed, data are necessary to quantify the effect of the change on the above parameters. For modifications to existing processes, a management of change review should occur. Data addressing issues resulting from these reviews are readily available by performing calorimetry experiments with the Advanced Reactive System Screening Tool and similar calorimeters. Examples of these applications are included in this article. © 2008 American Institute of Chemical Engineers Process Saf Prog, 2009
Protective effect of latex ofCalotropis procerain Freund's Complete Adjuvant induced monoarthritis
Authors: Kumar V. L. , Roy S.
Published: December 2008

The protective effect of latex ofCalotropis procerain Freund's Complete Adjuvant (FCA) induced monoarticular arthritis was evaluated in rats. Arthritis was induced by a single intra‐articular injection of 0.1 mL of 0.1% FCA in the right ankle joint. The effect of dried latex (DL, 200 and 400 mg/kg) and its methanol extract (MeDL, 50 and 500 mg/kg) following oral administration was evaluated on joint inflammation, hyperalgesia, locomotor function and histology at the time of peak inflammation. The effects of DL and MeDL were compared with antiinflammatory drugs phenylbutazone (100 mg/kg), prednisolone (20 mg/kg), rofecoxib (20 and 100 mg/kg) and immuno‐suppressant methotrexate (0.3 mg/kg). Daily oral administration of DL and its methanol extract (MeDL) produced a significant reduction in joint inflammation (about 50% and 80% inhibition) and associated hyperalgesia. The antihyperalgesic effect of MeDL was comparable to that of rofecoxib. Both DL and MeDL produced a marked improvement in the motility and stair climbing ability of the rats. The histological analysis of the arthritic joint also revealed significant reduction in oedema and cellular infiltration by MeDL that was comparable to that of rofecoxib. Thus, our study suggests that the latex of C. procera has the potential to be used as an antiarthritic agent. Copyright © 2008 John Wiley & Sons, Ltd.
Antiproliferative effects of different plant parts of Panax notoginseng on SW480 human colorectal cancer cells
Authors: Wang Chong‐Zhi , Xie Jing‐Tian , Fishbein Anna , Aung Han H. , He Hui , Mehendale Sangeeta R. , He Tong‐Chuan , Du Wei , Yuan Chun‐Su
Published: December 2008

The chemical constituents and antiproliferative effects on SW480 human colorectal cancer cells of different plant parts of P. notoginseng were evaluated. The contents of saponins in extracts from root, rhizome, flower and berry of P. notoginseng were determined using high performance liquid chromatography. The contents and proportions of saponins were different among the four plant parts. Using the cell counting method, the antiproliferative effects were evaluated and the results indicated all four extracts, at 0.05–1.0 mg/mL, showed concentration‐related antiproliferative effects on the cancer cells. The flower extract had stronger effects compared with the other three extracts; at 1.0 mg/mL, it inhibited the cell growth by 93.1% (p < 0.01). The antiproliferative effects of major saponins in notoginseng, notoginsenoside R1, ginsenosides Rb1, Rb3 and Rg1, were also evaluated, and the observed effects of major constituents support the pharmacological activities of extracts. The effects of notoginseng extracts on cell cycle and apoptosis of SW480 cells were determined using flow cytometry. Notoginseng extract can arrest the cells in S and G2/M phases. Remarkably apoptosis induction activities of notoginseng extracts were observed with the flower extract possessing the most potent effect, supporting the antiproliferative effect. Copyright © 2008 John Wiley & Sons, Ltd.
Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer's disease animal model
Authors: Dhanasekaran Muralikrishnan , Holcomb Leigh A. , Hitt Angie R. , Tharakan Binu , Porter Jami W. , Young Keith A. , Manyam Bala V.
Published: December 2008

PSAPP mice expressing the ‘Swedish’ amyloid precursor protein and the M146L presenilin 1 mutations are a well‐characterized model for spontaneous amyloid β plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid β 1–40 and 1–42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long‐term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid β pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd.
Inhibitory effects of the aqueous extract of Magnolia officinalis on the responses of human urinary bladder cancer 5637 cells in vitro and mouse urinary bladder tumors induced by N‐Butyl‐N‐(4‐hydroxybutyl) nitrosamine in vivo
Authors: Lee Se‐Jung , Cho Young‐Hwa , Park Keerang , Kim Eun‐Jung , Kang Bong‐Su , Jung Kyung‐Hwan , Kim Cheorl‐Ho , Kim Wun‐Jae , Moon Sung‐Kwon
Published: December 2008

This study investigated the anticancer activity of Magnolia officinalis on urinary bladder cancer in vitro and in vivo, and elucidated the mechanism of its activity. An aqueous extract of M. officinalis inhibited cell viability and DNA synthesis in cultured human urinary bladder cancer 5637 cells. Inhibition of proliferation was the result of apoptotic induction, because FACS analyses of 5637 cells treated with M. officinalis showed a sub‐G1 phase accumulation. M. officinalis extract also increased cytoplasmic DNA–histone complex dose‐dependently. These inhibitory effects were associated with the upregulation of proapoptotic molecules Bax, cytochrome c and caspase 3. Treatment of 5637 cells with M. officinalis extract suppressed the expression of matrix metalloproteinase 2 (MMP‐2) and MMP‐9, as revealed by zymographic and immunoblot analyses. When M. officinalis extract was given to mice simultaneously with the carcinogen N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine, which induces urinary bladder tumors, the size of the induced tumors was smaller. Finally, histological data indicated that the histological grade of carcinoma and the depth of invasion were dramatically decreased by treatment with M. officinalis extract in mice with N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine‐induced urinary bladder tumors. In conclusion, the findings showed that M. officinalis extract exhibited potential chemopreventive activity against urinary bladder tumor in vitro and in vivo. Copyright © 2008 John Wiley & Sons, Ltd.
In vitro anti‐adhesive activity of green tea extract against pathogen adhesion
Authors: Lee Ji‐Hye , Shim Jin Sun , Chung Mi‐Sook , Lim Seung‐Taik , Kim Kyung Hyun
Published: December 2008

Camellia sinensis polysaccharide has been reported to possess anti‐adhesive activity against pathogens. The present study was designed to investigate whether hot water extracts obtained from green tea leaves might inhibit pathogen adhesion to human or mouse cell lines. Green tea extract‐4 (CSI‐4) with the maximum yield of 4% (w/v) is composed of a major proportion of carbohydrates containing 40% uronic acids, but lack of catechins. It showed strong inhibitory activities against hemagglutination mediated by pathogens Helicobacter pylori, Propionibacterium acnes and Staphylococcus aureus with the minimum inhibitory concentrations of 0.01‐0.5 mg/mL. CSI‐4 further demonstrated an inhibitory effect on the adhesion of these pathogens to host cell lines with the IC50 values (50% inhibition of adhesion) of 0.14–2.3 mg/mL. It exhibited the highest activity against P. acnes, but no inhibitory effects were observed against Lactobacillus acidophilus, Bifidobacterium bifidum, Escherichia coli, or Staphylococcus epidermidis. Our results suggest that CSI‐4 may exert a selective anti‐adhesive effect against certain pathogenic bacteria with no adverse effects against beneficial or commensal bacteria. Copyright © 2008 John Wiley & Sons, Ltd.
Bioassay‐guided separation of citreorosein and other oestrogenic compounds From Polygonum cuspidatum
Authors: Zhang Caining , Wang Xuman , Zhang Xiaozhe , Zhang Yan , Xiao Hongbin , Liang Xinmiao
Published: December 2008

Citreorosein was isolated from P. cuspidatum as a new oestrogenic compound, together with emodin and its glucoside, by silica gel column chromatography and preparative high‐performance liquid chromatography sequentially. Oestrogenic activity was determined by a recombinant yeast assay. Copyright © 2008 John Wiley & Sons, Ltd.
Complement‐fixing activity of fulvic acid from Shilajit and other natural sources
Authors: Schepetkin Igor A. , Xie Gang , Jutila Mark A. , Quinn Mark T.
Published: December 2008

Shilajit has been used traditionally in folk medicine for the treatment of a variety of disorders, including syndromes involving excessive complement activation. Extracts of Shilajit contain significant amounts of fulvic acid (FA), and it has been suggested that FA is responsible for many therapeutic properties of Shilajit. However, little is known regarding the physical and chemical properties of Shilajit extracts, and nothing is known about their effects on the complement system. To address this issue, extracts of commercial Shilajit were fractionated using anion exchange and size‐exclusion chromatography. One neutral (S‐I) and two acidic (S‐II and S‐III) fractions were isolated, characterized and compared with standardized FA samples. The most abundant fraction (S‐II) was further fractionated into three sub‐fractions (S‐II‐1 to S‐II‐3). The van Krevelen diagram showed that the Shilajit fractions are the products of polysaccharide degradation, and all fractions, except S‐II‐3, contained type II arabinogalactan. All Shilajit fractions exhibited dose‐dependent complement‐fixing activity in vitro with high potency. Furthermore, a strong correlation was found between the complement‐fixing activity and carboxylic group content in the Shilajit fractions and other FA sources. These data provide a molecular basis to explain at least part of the beneficial therapeutic properties of Shilajit and other humic extracts. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of yeast hydrolysate on neuropeptide Y (NPY) and tryptophan hydroxylase (TPH) immunoreactivity in rats
Authors: Jung Eun Young , Kang Duk Ho , Suh Hyung Joo , Chang Un‐Jae
Published: December 2008

To investigate the appetite regulation mechanism of low and high molecular weight yeast hydrolysate, neuropeptide Y (NPY) and tryptophan hydroxylase (TPH) expressions were analyzed in the brains on rats using immunohistochemical method; normal diet (control), 0.1 g/kg (BY‐1) or 1.0 g/kg (BY‐2) of yeast hydrolysate below 10 kDa, 0.1 g/kg (AY‐1) or 1.0 g/kg (AY‐2) of yeast hydrolysate of 10–30 kDa. Body weight gain was lower in the BY‐2 (133.0 g) than in the control (150.1 g) (p < 0.05). Triacylglyceride, total cholesterol, and LDL‐cholesterol levels were lower in the BY‐2 as compared to control, BY‐1 and AY‐2 (p < 0.05). NPY staining intensities at paraventricular nucleus (PVN) were lower in the BY groups (BY‐1: 96.1, BY‐2: 88.6) as compared to the control (105.6) and AY groups (AY‐1: 110.5, AY‐2: 114.1) (p < 0.05). NPY expression at lateral hypothalamic area (LHA) was lower in the BY‐2 (92.3) than in the control (98.9) (p < 0.05). The BY groups (BY‐1: 143.9, BY‐2: 154.6) had higher TPH staining intensities at dorsal raphe (DR) than the AY‐2 (115.9) (p < 0.05). In conclusion, the results indicate that administering yeast hydrolysate of below 10 kDa to normal diet‐fed rats reduced body weight gain and serum lipids by altering NPY and TPH expressions. Copyright © 2008 John Wiley & Sons, Ltd.
Soy‐diet has beneficial effects on cardiovascular parameters that are independent of its lipid effect in male hypercholesterolemic rats
Authors: Fatehi M. , Farrokhfall K. , Davoudi S. , Collins T. M. , Fatehi‐Hassanabad Z.
Published: December 2008

Diet‐induced atherosclerosis is lower in animals fed soy protein. The effects of various soy components have been extensively studied; however, little is known about the effect of crude soybean feeding on hypercholesterolemia‐induced cardiovascular changes. This study investigated the effect of soy feeding on cardiovascular parameters in hypercholesterolemic male rats. Total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein cholesterol (HDL), and triglyceride (TG) were measured. Rats were randomly assigned to control, high cholesterol (HC, 2% cholesterol) or HC + soy (HC+S) diets. In the HC+S group, rats received HC diet for 10 weeks followed by 2 weeks of soybean feeding. Arterial blood pressure, TC, TG, LDL and HDL were measured. TC, TG and LDL were higher in HC rats and were not significantly reduced by soybean feeding. Soy feeding reversed the HC‐induced increase in arterial blood pressure and also restored the impaired vascular responses to acetylcholine in isolated aortic rings. Pre‐incubation of HC+S aortic rings with L‐NAME (10−5 M for 20 min) partially reduced the effects of soy on acetylcholine responses, indicating that the beneficial vascular effects of dietary soy are partially mediated via nitric oxide pathway. Copyright © 2008 John Wiley & Sons, Ltd.
The effects of methanol extract of Lobaria pulmonaria, a lichen species, on indometacin‐induced gastric mucosal damage, oxidative stress and neutrophil infiltration
Authors: Karakus Basak , Odabasoglu Fehmi , Cakir Ahmet , Halici Zekai , Bayir Yasin , Halici Mesut , Aslan Ali , Suleyman Halis
Published: December 2008

Lobaria pulmonaria, a lichen species, has been used in traditional medicine for the treatment of various diseases. This study was designed to determine the gastroprotective effect of the methanol extract of L. pulmonaria in an indometacin‐induced ulcer model in rats. The results showed that gastric lesions were significantly reduced in a dose‐dependent manner. Furthermore, the administration of indometacin caused a significant decrease in the levels of superoxide, glutathione peroxidase and reduced glutathione and an increase in the lipid peroxidation level. Administration of the lichen extract, however, produced an increase in the levels of these enzymes and a decrease in lipid peroxidation levels, although catalase and myeloperoxidase levels were unaffected. The present results suggested that Lobaria pulmonaria has a gastroprotective effect, probably due to reducing oxidative stress and neutrophil infiltration. Copyright © 2008 John Wiley & Sons, Ltd.
Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor
Authors: Wang Guei‐Jane , Huang Yeh‐Jeng , Chen Deng‐Hai , Lin Yun‐Lian
Published: December 2008

Hepatic fibrosis is an outcome of chronic liver diseases. The activation and proliferation of hepatic stellate cells (HSCs) is a key event in liver injury. The fruiting body of Ganoderma lucidum has long been a popular oriental medicine for treating liver diseases. The aim of this present study was to investigate the antiproliferative effects of the triterpenoid‐rich extract (GLT) of G. lucidum in a cell line of rat HSCs (HSC‐T6) stimulated with platelet‐derived growth factor (PDGF)‐BB. DNA synthesis was investigated by bromodeoxyuridine (BrdU) incorporation. Flow cytometry using propidium iodide (PI) labeling was carried out to analyse the cell cycle distribution and apoptosis. α‐Smooth muscle actin (α‐SMA) was used to evaluate extracellular matrix deposition, and western blotting was performed to measure cyclins D1 and D2, and phosphorylation of the PDGFβ‐receptor (PDGFβR), Akt and JNK. The results indicated that the GLT attenuated BrdU incorporation in a concentration‐dependent manner with an IC50 of 8.52 ± 0.33 µg/mL. The inhibitory effect of the GLT was associated with downregulation of cyclins D1 and D2, and PDGFβR and Akt phosphorylation, upregulation of JNK phosphorylation, and a reduction in α‐SMA expression. These results indicated that G. lucidum inhibits PDGF‐BB‐activated HSC proliferation possibly through blocking PDGFβR phosphorylation, thereby indicating its efficacy for preventing and treating hepatic fibrosis. Copyright © 2008 John Wiley & Sons, Ltd.
Antihyperglycemic and antioxidative effects of a herbal formulation of Radix Astragali, Radix Codonopsis and Cortex Lycii in a mouse model of type 2 diabetes mellitus
Authors: Chan Judy Yuet‐Wa , Lam Fung‐Chun , Leung Ping‐Chung , Che Chun‐Tao , Fung Kwok‐Pui
Published: December 2008

There is emerging evidence that the generation of reactive oxygen species (ROS), which leads to dysfunction of pancreatic β‐cells, is a major factor in the development of type 2 diabetes mellitus. Antioxidation is one of the therapeutic strategies to overwhelm the imbalance in ROS production. In this study, a herbal formulation SR10, comprising Radix Astragali, Radix Codonopsis and Cortex Lycii, was examined for its antidiabetic and antioxidative effects using the diabetic +db/+db mouse model. The results showed that SR10 was effective in decreasing the blood glucose level in chronic treatment by improving β‐cell function. The activities and expression of antioxidant enzymes, catalase and superoxide dismutase, were up‐regulated when treated with SR10. Moreover, SR10 treatment did not exhibit any toxic effect to the host. Copyright © 2008 John Wiley & Sons, Ltd.
Coronary vasodilator activity of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora, and its possible mechanism
Authors: Valle‐Mondragón L. del , Tenorio‐López F. A. , Torres‐Narváez J. C. , Zarco‐Olvera G. , Pastelín‐Hernández G.
Published: December 2008

The aim of this study was to investigate the biodynamic effects of vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals and its possible mechanism on the Langendorff isolated and perfused heart model. Vulgarenol (5 µm) caused a statistically significant decrease in coronary vascular resistance (15.21 ± 6.00 dyn s cm−5 vs 36.80 ± 5.01 dyn s cm−5, control group), increased nitric oxide release (223.01 ± 8.76 pmol/mL vs 61.00 ± 12.00 pmol/mL, control group) and cyclic guanosine monophosphate accumulation in left ventricular tissue samples (142.17 ± 8.41 pmol/mg of tissue vs 43.94 ± 5.00 pmol/mg of tissue, control group). Pre‐treatment with 3 µm gadolinium chloride hexahydrate, 100 µm Nω‐nitro‐l‐arginine methyl ester hydrochloride, and 10 µm 1H‐[1,2,4]oxadiazolo[4,2‐a]quinoxalin‐1‐one significantly abolished the vulgarenol‐induced coronary vascular resistance decrease, nitric oxide increased release and cGMP accumulation in left ventricular tissue samples. The results support the fact that nitric oxide and cyclic guanosine monophosphate are likely involved in the endothelium‐dependent coronary vasodilation. Copyright © 2008 John Wiley & Sons, Ltd.
Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo
Authors: Hong Si‐Jia , Wan Jian‐Bo , Zhang Yi , Hu Guang , Lin Hui‐Chao , Seto Sai Wang , Kwan Yiu‐Wa , Lin Zhi‐Xiu , Wang Yi‐Tao , Lee Simon Ming‐Yuen
Published: December 2008

Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. In fact, many diseases are associated with imbalance in the regulation of angiogenesis in which there is either excessive or insufficient blood vessel formation. Panax notoginseng, a blood circulation invigorating herb, is commonly used in traditional Chinese medicine to treat circulation‐related diseases. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo. The 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)5[(phenylamino)carbonyl]2H‐tetrazolium hydroxide (XTT) assay and microscopic cell counting demonstrated that the extract was able to stimulate the proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube branches were significantly increased in PNS treatment groups. PNS was also shown to promote changes in the subintestinal vessels, a feature of angiogenesis, in zebrafish. In addition, by using real‐time polymerase chain reaction (PCR), PNS was found to enhance vascular endothelial growth factor (VEGF) and kinase‐domain region/fetal liver kinase‐1 in mice (KDR/Flk‐1) mRNA expression, and the PNS‐induced HUVECs proliferation could be abolished by a KDR/Flk‐1 inhibitor. Furthermore, the proliferation of HUVECs induced by PNS was significantly attenuated by inhibitors of PI3K‐Akt‐eNOS. All the results suggest that PNS can promote angiogenesis, and that the proangiogenic effects involve the VEGF‐KDR/Flk‐1 and PI3K‐Akt‐eNOS signaling pathways. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of adlay (Coix lachryma‐jobiL. var.ma‐yuenStapf.) hull extracts on testosterone release from rat Leydig cells
Authors: Hsia Shih‐Min , Tseng Yi‐Wen , Wang Shyi‐Wu , Kuo Yueh‐Hsiung , Huang Din‐Wen , Wang Paulus S. , Chiang Wenchang
Published: December 2008

Adlay has been used as a traditional Chinese medicine for the treatment of many diseases. However, few studies have reported the effects of adlay seeds on the endocrine system. In the present study, the effects of methanol extracts of adlay hull (AHM) on testosterone synthesis were studied. Rat Leydig cells were incubated with different reagents including human chorionic gonadotropin, 8‐bromo‐adenosine‐3′,5′‐cyclic monophosphate, forskolin, A23187, progesterone and androstenedione in the presence or absence of AHM. The rat anterior pituitary (AP) gland was treated with gonadotropin‐releasing hormone (GnRH)in vitroin the presence or absence of AHM, and the concentrations of luteinizing hormone (LH) in the media were measured. AHM decreased testosterone release via the inhibition of (1) the PKA and PKC signal transduction pathways, (2) 17β‐HSD enzyme activity in rat Leydig cells, and (3)in vitroGnRH‐induced LH secretion. Copyright © 2008 John Wiley & Sons, Ltd.
Trifolium L. – A review on its phytochemical and pharmacological profile
Authors: Sabudak Temine , Guler Necmettin
Published: December 2008

Plants from the genus Trifolium have been used in traditional medicine by many cultures. In Turkish folk medicine, for example, some Trifolium species are used for their expectorant, analgesic, antiseptic properties and also to treat rheumatic aches. Some species are also grown as pasture crops for animals in the Mediterranean. The high quercetin concentration and soyasaponin occurrence make the seeds of some Trifolium species a potential source of health beneficial phytochemicals for use in human nutrition. However, Trifolium pratense has also gained popularity due to research into its use for the treatment for menopausal symptoms. This paper provides an overview of the phytochemical and pharmacological profile of Trifolium species. Copyright © 2008 John Wiley & Sons, Ltd.
Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation
Authors: Sehmisch S. , Boeckhoff J. , Wille J. , Seidlova‐Wuttke D. , Rack T. , Tezval M. , Wuttke W. , Stuermer K. M. , Stuermer E. K.
Published: December 2008

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3‐month‐old male rats were orchidectomized and divided into five groups. The groups either received soy‐free food (C), estradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically.

The AC high group reached 87% of the biomechanical values of the estradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with estradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with estradiol supplementation.

Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone. Copyright © 2008 John Wiley & Sons, Ltd.
Mangifera indica extract (Vimang) impairs aversive memory without affecting open field behaviour or habituation in rats
Authors: Preissler Thales , Martins Márcio Rodrigo , Pardo‐Andreu Gilberto L. , Henriques João Antônio Pêgas , Quevedo João , Delgado Rene , Roesler Rafael
Published: December 2008

Vimang is an aqueous extract of Mangifera indica L, used in Cuba for the treatment of immunopathological disorders. Increasing evidence from preclinical studies indicates that Vimang displays antioxidant, antiallergic, analgesic and antiinflammatory actions. The present study investigated the effects of systemic administration of Vimang on behavioural outcomes of neurological function in rats. A single oral administration of Vimang produced an impairment of short‐ and long‐term retention of memory for aversive training when given either 1 h pretraining or immediately posttraining, but not 8 h posttraining. Vimang did not affect open field behaviour or habituation. The results indicate that Vimang might induce deficits of emotionally motivated memory without affecting nonassociative memory, locomotion, exploratory behaviour or anxiety. Copyright © 2008 John Wiley & Sons, Ltd.
Genistein down‐regulates the constitutive activation of nuclear factor‐κB in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis
Authors: He Hui , Chen Laurie , Zhai Ming , Chen John Z. S.
Published: December 2008

Because of the central role of transcription factor nuclear factor‐κB (NF‐κB) in cell survival and proliferation in human multiple myeloma, the possibility of using it as a target for myeloma treatment was explored using genistein, an agent known to have very little or no toxicity in humans. It was found that NF‐κB was constitutively active in two human myeloma cell lines examined and that genistein, a chemopreventive agent, down‐regulated NF‐κB in two cell lines as indicated by the electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. Two myeloma cell lines showed constitutively active Akt phosphorylation. Genistein suppressed the constitutive Akt phosphorylation. Genistein also down‐regulated the expression of NF‐κB‐regulated gene products, including bcl‐2, bcl‐xl, cyclin D1 and ICAM‐1. This led to the suppression of proliferation and induction of apoptosis. Overall, the results indicate that genistein down‐regulates NF‐κB and phospho‐Akt in human myeloma cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of myeloma patients with this pharmacologically safe agent. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of Microdesmis keayana alkaloids on vascular parameters of erectile dysfunction
Authors: Zamblé Alexis , Martin‐Nizard Françoise , Sahpaz Sevser , Reynaert Marie‐Line , Staels Bart , Bordet Régis , Duriez Patrick , Gressier Bernard , Bailleul François
Published: December 2008

Microdesmis keayana (Pandaceae) is an African tropical plant whose roots are used in traditional medicine for erection impairment but the compounds responsible for its action are unknown. Two major alkaloids recently isolated from the roots of M. keayana, keayanidine B and keayanine, were tested for vasorelaxing properties using isolated rat aortic rings precontracted by phenylephrine to confirm its traditional use. Influence of the alkaloids on the endothelial production of endothelial nitric oxide synthase (eNOS) was measured by quantitative polymerase chain reaction (QPCR) analysis. Scavenging activities were assessed versus 1,1‐diphenyl‐2‐picrylhydrazyle (DPPH) and reactive oxygen species (ROS) such as superoxide anion (O−) and hydrogen peroxide (H2O2) in cell‐free and cellular systems.

The results showed that keayanidine B and keayanine had significant vasorelaxing properties. This effect could be due to their strong antioxidant activity versus O− and H2O2 and to their stimulation of eNOS mRNA expression. Therefore these alkaloids could indirectly stimulate NO production in the vascular bed and would explain the traditional use of M. keayana in erectile dysfunction. Copyright © 2008 John Wiley & Sons, Ltd.
Screening of selected food and medicinal plant extracts for pancreatic lipase inhibition
Authors: Slanc Petra , Doljak Bojan , Kreft Samo , Lunder Mojca , Janeš Damjan , Štrukelj Borut
Published: December 2008

Lipids are important components in human nutrition; however, their increased intake contributes to the development of obesity and can lead to multiple long‐term complications. Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) is a key enzyme for the absorption of dietary triglycerides. Interference with fat hydrolysis results in the reduced utilization of ingested lipids, therefore inhibition of lipases decreases fat absorption. Extracts from 106 species of medicinal plants, vegetables and fruits were screened for potential lipase inhibitory activity. p‐Nitrophenylpalmitate and 5‐bromo‐4‐chloro‐3‐indoxylpalmitate were used as substrates in an in vitro test with crude porcine pancreatic lipase. Bearberry (Arctostaphylos uva‐ursi), garden pea (Pisum sativum), Norway spruce (Picea abies) and large‐leaved lime (Tilia platyphyllos) extracts were the most active. Additionally, the activity of selected extracts with removed polyphenols was measured. Extracts of bearberry, garden pea and large‐leaved lime are a promising source for developing functional foods or isolating active compounds. Copyright © 2008 John Wiley & Sons, Ltd.
Genistein suppresses adipogenesis of 3T3‐L1 cells via multiple signal pathways
Authors: Zhang Meng , Ikeda Katsumi , Xu Jin‐Wen , Yamori Yukio , Gao Xiu‐Mei , Zhang Bo‐Li
Published: December 2008

Genistein, an isoflavone, was shown to have therapeutic effects for obesity, diabetes and cardiovascular diseases. This study investigated the effect and underlying mechanism of genistein on adipogenesis in 3T3‐L1 preadipocytes. Genistein inhibited lipid accumulation and decreased the nonesterified fatty acid (NEFA) content of 3T3‐L1 on day 6 after the induction of differentiation with methylisobutylxanthine, dexamethasone and insulin (MDI). Genistein recovered nitric oxide (NO) release suppressed by MDI and the results were consistent with the expression of endothelial NO synthase (eNOS) assayed by western blotting. Pretreatment with genistein inhibited the phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK) stimulated with 10 µg/mL of insulin. Furthermore, genistein inhibited the expression of fatty acid synthase (FAS) from 178% of the MDI group to 74%. SB203580, a p38 inhibitor, mimicked the FAS inhibition effect of genistein, suggesting that the inhibitory effect of genistein on FAS was partially via the p38 pathway. On the other hand, genistein abolished the phosphorylation of janus‐activated kinase 2 (JAK2) in response to MDI. AG490, a JAK2 inhibitor, suppressed the expression of CCAAT/enhancer binding protein alpha (C/EBPα), a marker of adipocyte differentiation. The findings suggest that genistein attenuates the differentiation of 3T3‐L1 involving multiple signal pathways. Copyright © 2008 John Wiley & Sons, Ltd.
Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb.
Authors: Hevesi B. T. , Houghton P. J. , Habtemariam S. , Kéry Á.
Published: December 2008

Epilobium parviflorum Schreb. (Onagraceae) is used for the treatment of benign prostatic hyperplasia (BPH), but its biological action is not entirely identified. This paper aims to report data on E. parviflorum with respect to its antioxidant and antiinflammatory effects. The aqueous acetone extract of E. parviflorum showed higher antioxidant effect in the DPPH assay than well known antioxidants and inhibited the lipid peroxidation determined by the TBA assay (IC50 = 2.37 ± 0.12 mg/mL). In concentrations of 0.2–15.0 µg/mL the extract possessed a protective effect, comparable to catalase (250 IU/mL), against oxidative damage, generated in fibroblast cells. In the COX inhibition assay E. parviflorum decreased the PGE2 release, so showing inhibition of the COX‐enzyme (IC50 = 1.4 ± 0.1 µg/mL). Copyright © 2008 John Wiley & Sons, Ltd.