Phytomedicine - Articles in Press

Investigation of sanguinarine and chelerythrine effects on LPS-induced inflammatory gene expression in THP-1 cell line - Corrected Proof

K. Pěnčíková, P. Kollár, V. Müller Závalová, E. Táborská, J. Urbanová, J. Hošek — 2012-05-16

Graphical abstract: Abstract: Quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine have been used in folk medicine for their wide range of useful properties. One of their major effect is also anti-inflammatory activity, that is not clarified in detail.This study focused on the ability of these alkaloids to modulate the gene expression of pro-inflammatory tumour necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1, also known as CCL-2), interleukin (IL)-6, IL-1β and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL-10. The effect of these alkaloids was compared with that of conventional drug prednisone.Human monocyte-derived macrophages were pre-treated with alkaloids or prednisone and inflammatory reaction was induced by lipopolysaccharide. Changes of gene expression at the transcriptional level of mentioned cytokines were measured.In our study mainly affected pro-inflammatory cytokines were CCL-2 and IL-6. Two hours after LPS stimulation, cells influenced by sanguinarine and chelerythrine significantly declined the CCL-2 expression by a factors of 3.5 (p<0.001) and 1.9 (p<0.01); for those treated with prednisone the factor was 5.3 (p<0.001). Eight hours after LPS induction, both alkaloids significantly diminished the CCL-2 expression. The lower expression was found for sanguinarine – lower by a factor of 4.3 than for cells treated with the vehicle (p<0.001).Two hours after LPS stimulation, cells treated with sanguinarine decreased the IL-6 mRNA level by a factor of 3.9 (p<0.001) compared with cells treated with the vehicle. Chelerythrine decreased the level of IL-6 mRNA by a factor of 1.6 (p<0.001). Sanguinarine decreased gene expression of CCL-2 and IL-6 more than chelerythrine and its effect was quite similar to prednisone. Four hours after LPS stimulation, cells pre-treated with sanguinarine exhibited significantly higher expression (a factor of 1.7, p<0.001) of IL-1RA than cells without sanguinarine treatment. Our results help to clarify possible mechanisms of action of these alkaloids in the course of inflammation.

Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice - Corrected Proof

Chi-Tun Ruan, Sio-Hong Lam, Tzong-Cherng Chi, Shoei-Sheng Lee, Ming-Jai Su — 2012-05-11

Graphical abstract: Abstract: Diabetes mellitus (DM) often leads to disability from vascular complications and neurological complications. Tinospora crispa has been widely used in Asia and Africa as a remedy for diabetes and other diseases. In this study, we investigated the hypoglycemic actions of borapetoside C isolated from T. crispa, and the mechanisms underlying its actions. Acute treatment with borapetoside C (5mg/kg, i.p.) attenuated the elevated plasma glucose induced by oral glucose in normal and type 2 DM (T2DM) mice. Compared to the effect of injected insulin (0.5IU/kg), borapetoside C caused a more prominent increase of glycogen content in skeletal muscle of T2DM mice, but a less increase in type 1 DM (T1DM) mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, i.p.) plus insulin enhanced insulin-induced lowering of the plasma glucose level and insulin-induced increase of muscle glycogen content. Continuous treatment with 5mg/kg borapetoside C (twice daily) for 7days increased phosphorylation of insulin receptor (IR) and protein kinase B (Akt) as well as the expression of glucose transporter-2 (GLUT2) in T1DM mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, twice daily) plus insulin for 7days enhanced insulin-induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice. This study proved that borapetoside C can increase glucose utilization, delayed the development of insulin resistance and enhanced insulin sensitivity. The activation of IR-Akt-GLUT2 expression and the enhancement of insulin sensitivity may contribute to the hypoglycemic action of borapetoside C in diabetic mice.

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures - Corrected Proof

2012-05-09

Abstract: Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP+) toxicity. MPP+ is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP+ (10μM) was administered for 48h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10μM.All cannabinoids exhibited in vitro antioxidative action ranging from 669±11.1 (THC), 16±3.2 (THCA) to 356±29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1–20% at concentrations of 0.01–10μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count.Exposure of cultures to 10μM of MPP+ for 48h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP+ treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10μM lead to significantly increased cell counts to 123% and 117%, respectively. Even though no significant preservation or recovery of neurite outgrowth to control values could be observed, our data show that cannabinoids THC and THCA protect dopaminergic neurons against MPP+ induced cell death.

α-Santalol, a derivative of sandalwood oil, induces apoptosis in human prostate cancer cells by causing caspase-3 activation - Corrected Proof

2012-05-09

Graphical abstract: α-Santalol, a major component of sandalwood oil showed anti-cancer activity in prostate cancer cells by inducing apoptosis and activation of caspase-3 activity. These results provide new evidence in support of α-santalol as a promising agent for preventing prostate cancer.Abstract: The anticancer effects of α-santalol, a major component of sandalwood oil, have been reported against the development of certain cancers such as skin cancer both in vitro and in vivo. The primary objectives of the current study were to investigate the cancer preventive properties of α-santalol on human prostate cancer cells PC-3 (androgen independent and P-53 null) and LNCaP (androgen dependent and P-53 wild-type), and determine the possible mechanisms of its action. The effect of α-santalol on cell viability was determined by trypan blue dye exclusion assay. Apoptosis induction was confirmed by analysis of cytoplasmic histone-associated DNA fragmentation using both an apoptotic ELISA kit and a DAPI fluorescence assay. Caspase-3 activity was determined using caspase-3 (active) ELISA kit. PARP cleavage was analyzed using immunoblotting. α-Santalol at 25–75μM decreased cell viability in both cell lines in a concentration and time dependent manner. Treatment of prostate cancer cells with α-santalol resulted in induction of apoptosis as evidenced by DNA fragmentation and nuclear staining of apoptotic cells by DAPI. α-Santalol treatment also resulted in activation of caspase-3 activity and PARP cleavage. The α-santalol-induced apoptotic cell death and activation of caspase-3 was significantly attenuated in the presence of pharmacological inhibitors of caspase-8 and caspase-9. In conclusion, the present study reveals the apoptotic effects of α-santalol in inhibiting the growth of human prostate cancer cells.

Hypocholesterolemia of Rhizoma Coptidis alkaloids is related to the bile acid by up-regulated CYP7A1 in hyperlipidemic rats - Corrected Proof

2012-05-03

Graphical abstract: Coptis alkaloids extract (CAE) showed significant hypocholesterolemic effect at least by (1) up-regulating the gene expression and activity of CYP7A1 which promotes the conversion of cholesterol (Ch) into bile acid (BA); (2) increasing the cholesterol excretion in feces. CAE up-regulating the gene expression of CYP7A1 might be related to the positive regulation of PPARα and the negative modulation of FXR in the livers of high lipid diet-induced hyperlipidemic rats.Abstract: This study is to investigate the cholesterol-lowering effect and the new mode of action of coptis alkaloids on high lipid diet-induced hyperlipidemic rats. Coptis alkaloids extract (CAE) was prepared by alcohol extraction from Rhizoma Coptidis that have been quality-controlled according to the protocol. The cholesterol-lowering effect of CAE was evaluated on SD rats fed with high-lipid diet. Serum level of lipid, Bile acid and cholesterol in the liver and feces of the rats were measured using colorimetric assay kit. RT-PCR and Western blot were used to analyze the mRNA and protein expression of cholesterol metabolism-related genes including cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptor-alpha (PPARα) and farnesoid X receptor (FXR) in the livers of the rats. A HPLC analysis was used to assess the activity of CYP7A1. The results showed that CAE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C). CYP7A1 gene expression and its activity was up-regulated dose-dependently acompanying with the increased level of bile acid and the reduced cholesterol level in the livers of the CAE treated hyperlipidemic rats. Meanwhile, the mRNA expression of PPARα was also up-regulated in dose-dependent way acompanying the down-modulation of the FXR mRNA expression in the livers of the CAE treated hyperlipidemic rats.The results indicate that the cholesterol-lowering effect of coptis alkaloid extract is at least partly attributed to its promoting the cholesterol conversion into bile acids by up-regulating the gene expression of CYP7A1 and thus increasing its activity in the liver of the hyperlipidemic rats, which might related to the positive regulation of PPARα and the negative modulation of FXR.

β-Amyrin acetate and β-amyrin palmitate as antidyslipidemic agents from Wrightia tomentosa leaves - Corrected Proof

2012-04-30

Abstract: The ethanolic extract and fractions of Wrightia tomentosa Roem. & Schult (Apocynaceae) leaves were tested in vivo for their antidyslipidemic activity in high fat diet (HFD) induced dyslipidemic hamsters. Activity guided isolation resulted in identification of antidyslipidemic compounds β-AA and β-AP. Compounds β-AA and β-AP decrease the levels of LDL by 36% and 44%, and increase the HDL-C/TC ratio by 49% and 28%, respectively, at a dose of 10mg/kg. In addition, the isolated compounds β-AA and β-AP showed significant HMG-CoA-reductase inhibition, which was further established by docking studies.

Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells - Corrected Proof

2012-04-27

Graphical abstract: Abstract: Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250μM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50μM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents.

An in vitro assessment of the effect of Athrixia phylicoides DC. aqueous extract on glucose metabolism - Corrected Proof

N. Chellan, C.J.F. Muller, D. de Beer, E. Joubert, B.J. Page, J. Louw — 2012-04-20

Abstract: Athrixia phylicoides DC. is an aromatic shrub indigenous to the eastern parts of Southern Africa. Indigenous communities brew “bush tea” from dried twigs and leaves of A. phylicoides, which is consumed as a beverage and used for its medicinal properties. Plant polyphenols have been shown to be beneficial to Type 2 diabetes mellitus (T2D) and obesity. Aqueous extracts of the plant have been shown to be rich in polyphenols, in particular phenolic acids, which may enhance glucose uptake and metabolism. The aim of this study was to determine the phenolic composition of a hot water A. phylicoides extract and assess its in vitro effect on cellular glucose utilisation. The most abundant phenolic compounds in the extract were 6-hydroxyluteolin-7-O-glucoside, chlorogenic acid, protocatechuic acid, a di-caffeoylquinic acid and a methoxy-flavonol derivative. The extract increased glucose uptake in C2C12, Chang and 3T3-L1 cells, respectively. Intracellular glucose was utilised by both oxidation (C2C12 myocytes and Chang cells; p<0.01 and p<0.05, respectively) and by increased glycogen storage (Chang cells; p<0.05). No cytotoxicity was observed in Chang cells at the concentrations tested. The effects of the extract were not dose-dependent. A. phylicoides aqueous extract stimulated in vitro glucose uptake and metabolism, suggesting that consumption of this phenolic-rich extract could potentially ameliorate metabolic disorders related to obesity and T2D.

Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models - Corrected Proof

2012-04-20

Graphical abstract: Abstract: Antrodia camphorata (AC) is a native Taiwanese mushroom which is used in Asian folk medicine as a chemopreventive agent. The triterpenoid-rich fraction (FEA) was obtained from the ethanolic extract of AC and characterized by high performance liquid chromatography (HPLC). FEA caused DNA damage in leukemia HL 60 cells which was characterized by phosphorylation of H2A.X and Chk2. It also exhibited apoptotic effect which was correlated to the enhancement of PARP cleavage and to the activation of caspase 3. Five major triterpenoids, antcin K (1), antcin C (2), zhankuic acid C (3), zhankuic acid A (4), and dehydroeburicoic acid (5) were isolated from FEA. The cytotoxicity of FEA major components (1–5) was investigated showing that dehydroeburicoic acid (DeEA) was the most potent cytotoxic component. DeEA activated DNA damage and apoptosis biomarkers similar to FEA and also inhibited topoisomerase II. In HL 60 cells xenograft animal model, DeEA treatment resulted in a marked decrease of tumor weight and size without any significant decrease in mice body weights. Taken together, our results provided the first evidence that pure AC component inhibited tumor growth in vivo model backing the traditional anticancer use of AC in Asian countries.

Preconditioning of brain slices against hypoxia induced injury by a Gynostemma pentaphyllum extract – Stimulation of anti-oxidative enzyme expression - Corrected Proof

L. Schild, T. Cotte, G. Keilhoff, R. Brödemann — 2012-04-19

Abstract: A short period of hypoxia/hypoglycaemia (oxygen and glucose deprivation, OGD) induced by perfusion with O2/glucose-free medium caused immediate loss and incomplete restoration of evoked field potentials in the CA1 region of transverse hippocampus slices. OGD-dependent decrease in evoked field potentials can be prevented by a proceeding short OGD event (preconditioning). We report about a study investigating the effect of an ethanolic Gynostemma pentaphyllum extract on evoked field potentials when administered before the OGD episode. Using this procedure, the extract completely protected the cells of the slices from functional injury. In an astroglia rich cell culture the ethanolic Gynostemma pentaphyllum extract caused within 48h of cultivation increased protein and activity levels of the anti-oxidative enzymes manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPx). Consequently, the cellular H2O2 concentration remained at a low level. These data suggest that the Gynostemma pentaphyllum-mediated increase in antioxidative enzyme activities may contribute to the protection of transverse hippocampus slices from OGD induced functional injury. Our results demonstrate that the prophylactic administration of the ethanolic extract from Gynostemma pentaphyllum has a high potential to protect from ischemia/reperfusion injury.

Inhibition of cholinesterase by essential oil from food plant - Corrected Proof

Wantida Chaiyana, Siriporn Okonogi — 2012-04-17

Abstract: Inhibition of cholinesterase has attracted much attention recently because of its potential for the treatment of Alzheimer's disease. In this work, the anticholinesterase activities of plant oils were investigated using Ellman's colorimetric method. The results indicate that essential oils obtained from Melissa officinalis leaf and Citrus aurantifolia leaf showed high acetylcholinesterase and butyrylcholinesterase co-inhibitory activities. C. aurantifolia leaf oil revealed in this study has an IC50 value on acetylcholinesterase and butyrylcholinesterase of 139±35 and 42±5μg/ml, respectively. GC/MS analysis revealed that the major constituents of C. aurantifolia leaf oil are monoterpenoids including limonene, l-camphor, citronellol, o-cymene and 1,8-cineole.

Fucoidan extract derived from Undaria pinnatifida inhibits angiogenesis by human umbilical vein endothelial cells - Corrected Proof

2012-04-17

Abstract: In recent years, anti-angiogenic therapy has become an effective strategy for inhibiting tumor growth. Fucoidan is a class of fucose-enriched sulfated polysaccharides found in brown algae, and it is known to have strong anti-tumor property. Using a human umbilical vein endothelial cells (HUVEC)-based cell culture model, the present study investigated the anti-angiogenic activity of fucoidan extracted from the brown seaweed Undaria pinnatifida. Treatment of HUVECs with various concentrations of fucoidan resulted in significant inhibition of cell proliferation, cell migration, tube formation and vascular network formation. However, significant inhibition of cell proliferation only occurred with longer treatment time (48h instead of 24h or less). About 40% of cell proliferation and cell migration and 61% of tube formation by HUVECs were inhibited by 400μg/ml fucoidan, the maximum concentration tested. These results appeared to suggest that modulation of angiogenesis by fucoidan might not occur through growth inhibition and apoptosis. Ex vivo angiogenesis assay demonstrated that at 100μg/ml, fucoidan caused significant reduction in microvessel outgrowth. Western blot and RT-PCR analyses indicated that at 400μg/ml, fucoidan significantly reduced the expression of the angiogenesis factor VEGF-A in the suppression of angiogenesis activity. Our results showed that fucoidan isolated from U. pinnatifida may have a new therapeutic potential in the prevention angiogenesis-related diseases.

Efficacy of 20-OH-ecdysone on hepatic key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats - Corrected Proof

2012-04-09

Abstract: The aim of the present investigation was to evaluate the anti-diabetic activity of 20-OH-ecdysone on glucose metabolic key enzymes in control and streptozotocin induced diabetic rats. On oral administration of 20-OH-ecdysone at a dose of 5mg/kg body weight per day to diabetic rats for 30 days resulted in a significant decrease in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and an increase in the levels of insulin and hemoglobin. Administration of 20-OH-ecdysone showed significant increase in the levels of glycolytic enzyme (hexokinase) and hepatic shunt enzyme (glucose-6-phophate dehydrogenase) whereas significant decrease in the levels of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in diabetic treated rats. Furthermore, protection against body weight loss of diabetic animals also observed. This study indicates that the administration of 20-OH-ecdysone to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels. A comparison was made between the action of 20-OH-ecdysone and antidiabetic drug-glibenclamide. The effects produced by the 20-OH-ecdysone were comparable to that of glibenclamide.

Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract - Corrected Proof

2012-04-06

Abstract: Garlic (Allium sativum) is considered one of the best disease-preventive foods. We evaluated in vitro the effect of a commercial garlic powder (GP), at concentrations of 0.1% and 1% (w/v), upon the viability of representative gut bacteria. In pure culture studies, Lactobacillus casei DSMZ 20011 was essentially found to be resistant to GP whereas a rapid killing effect of between 1 and 3logCFU/ml reduction in cell numbers was observed with Bacteroides ovatus, Bifidobacterium longum DSMZ 20090 and Clostridium nexile A2-232. After 6h incubation, bacterial numbers increased steadily and once the strains became resistant they retained their resistant phenotype upon sub-culturing. A colonic model was also used to evaluate the effect of GP on a mixed bacterial population representing the microbiota of the distal colon. Lactic acid bacteria were found to be more resistant to GP compared to the clostridial members of the gut microbiota. While for most bacteria the antimicrobial effect was transient, the lactobacilli showed a degree of resistance to garlic, indicating that its consumption may favour the growth of these beneficial bacterial species in the gut. Garlic intake has the potential to temporarily modulate the gut microbiota.

Polydatin protects learning and memory impairments in a rat model of vascular dementia - Corrected Proof

2012-04-06

Graphical abstract: Abstract: Polydatin is one of the most common encountered stilbenes of nature and a key component of the Chinese herb Polygonum cuspidatum. This study is to investigate the effects of polydatin on learning and memory impairments induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Both common carotid arteries and both vertebral arteries occlusion (four-vessel occlusion, 4-VO) induced severe cognitive deficits tested by water maze task, along with oxidative stress in hippocampus. Oral administration of polydatin for 30 days markedly attenuated cognitive deficits compared with the control (p<0.05). Biochemical determination revealed that polydatin decreased the production of malondialdehyde (MDA) and significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, polydatin effectively alleviated the injuries of cultured neurons induced by oxygen-glucose deprivation (OGD). These results suggest that polydatin exhibit therapeutic potential for vascular dementia, which is most likely related, at least in part, to its anti-oxidant activity and the direct protection of neurons.

Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin - Corrected Proof

Duo Wu, Wei Wen, Chun-Li Qi, Ru-Xia Zhao, Jun-Hua Lü, Chun-Yan Zhong, Yi-Yu Chen — 2012-04-06

Abstract: Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250mg/kg metformin-treated, iv and v) 100 and 200mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.

Cardioprotective effect of total paeony glycosides against isoprenaline-induced myocardial ischemia in rats - Corrected Proof

2012-04-06

Abstract: Paeoniae radix is a traditional Chinese medicinal herb for treating some diseases; important components are total paeony glycosides (TPGs), an approved drug by the State Food and Drug Administration (SFDA) for the therapy of rheumatoid arthritis (RA). We firstly reported myocardial benefits of TPGs previously, and the present study is to further investigate the underlying mechanisms for preventing oxidative damage in cardiomyopathy. We measured the capacity of TPGs to scavenge free radicals in vitro. Then 60 SD rats were randomly divided into five groups: (1) a normal control group, (2) an isoprenaline (ISO)-induced myocardial ischemic model group, (3) a TPG treatment group (TPGs 269.4mg/kg delivered by intragastric administration for 3 days before ISO administration and TPGs 449mg/kg delivered for 3 days after ISO administration), (4) a TPG therapy group (TPGs 449mg/kg delivered for 3 days after ISO administration), and (5) a positive control group (propranolol 15mg/kg for 3 days after ISO administration). The ISO-induced myocardial ischemic model was established by subcutaneous injection of 1mg/kg/8h ISO (2 times). The activities of myocardial enzymes, including glutamic oxaloacetic transaminase (GOT), creatine kinase (CK), lactate dehydrogenase (LDH), antioxidant enzyme superoxide dismutase (SOD) as well as the content of lipid peroxidation product malondialdehyde (MDA) were detected. We found that TPGs potently eliminated hydroxyl radicals and superoxide in vitro using ESR assays. Compared with model rats, TPG treatment, TPG therapy and the positive control treatment exhibited significantly reduced activities of GOT, LDH, and CK (p<0.01), increased activity of SOD (p<0.01) and lower levels of MDA (p<0.05). More interestingly, the protective effect of TPG treatment was even better than that of propranolol. These results suggest that TPGs significantly ameliorate ISO-induced myocardial ischemia and their action might be through reducing oxidative stress in ischemic myocardium.

Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1α and caspase-3 mechanisms - Corrected Proof

2012-04-06

Abstract: Curcumin, a yellow pigment derived from Curcuma longa Linn, has been favored by the Eastern as dietary ingredients for centuries. During the past decade, extensive investigations have revealed curcumin sensitized various chemotherapeutic agents in human breast, colon, pancreas, gastric, liver, brain and hematological malignant disorders in vivo and in vitro. Several pathways and specific targets including NF-κB, STAT3, COX-2, Akt and multidrug resistant protein have been identified to facilitate curcumin as a chemosensitizer. Recent studies suggest HIF-1α participated in the development of drug resistance in cancer cells and targeting HIF-1α either by RNAi or siRNA successfully overcame chemotherapeutic resistance. To investigate the mechanism basis of curcumin as a chemosensitizer in lung cancer, we examined curcumin's effects on HIF-1α in cis-platin (DDP) sensitive A549 and resistant A549/DDP cell lines by RT-PCR and Western blot. HIF-1α in A549/DDP cells was found to be overexpressed at both mRNA and protein levels together with a poor response to DDP. Results from transient transfection and flow cytometry showed the HIF-1α abnormality contributed to DDP resistance in A549/DDP lung cancer cells. Combined curcumin and DDP treatment markedly inhibited A549/DDP cells proliferation, reversed DDP resistance and triggered apoptotic death by promoting HIF-1α degradation and activating caspase-3, respectively. Expression of HIF-1α-dependent P-gp also seemed to decrease as response to curcumin in a dose-dependent manner. Our findings shed light on drug resistant reversing effect of curcumin in lung cancer cells by inhibiting HIF-1α expression and activating caspase-3.

Is lavender an anxiolytic drug? A systematic review of randomised clinical trials - Corrected Proof

R. Perry, R. Terry, L.K. Watson, E. Ernst — 2012-04-05

Abstract: Background: Lavender (Lavandula angustifolia) is often recommended for stress/anxiety relief and believed to possess anxiolytic effects.Aim: To critically evaluate the efficacy/effectiveness of lavender for the reduction of stress/anxiety.Methods: Seven electronic databases were searched to identify all relevant studies. All methods of lavender administration were included. Data extraction and the assessment of the methodological quality of all included trials were conducted by two independent reviewers.Results: Fifteen RCTs met the inclusion criteria. Two trials scored 4 points on the 5-point Jadad scale, the remaining 13 scored two or less. Results from seven trials appeared to favour lavender over controls for at least one relevant outcome.Conclusion: Methodological issues limit the extent to which any conclusions can be drawn regarding the efficacy/effectiveness of lavender. The best evidence suggests that oral lavender supplements may have some therapeutic effects. However, further independent replications are needed before firm conclusions can be drawn.

Ethanol extracts of fruiting bodies of Antrodia cinnamomea exhibit anti-migration action in human adenocarcinoma CL1-0 cells through the MAPK and PI3K/AKT signaling pathways - Corrected Proof

2012-04-05

Graphical abstract: Abstract: Cancer metastasis is a primary cause of cancer death. Antrodia cinnamomea (A. cinnamomea), a medicinal mushroom in Taiwan, has been shown antioxidant and anticancer activities. In this study, we first observed that ethanol extract of fruiting bodies of A. cinnamomea (EEAC) exerted a concentration-dependent inhibitory effect on migration and motility of CL1-0 cells in the absence of cytotoxicity. The results of a gelatin zymography assay showed that A. cinnamomea suppressed the activity of matrix metalloproteinase (MMP)-2 and MMP-9 in a concentration-dependent manner. Western blot results demonstrated that treatment with A. cinnamomea decreased the expression of MMP-9 and MMP-2; while the expression of the endogenous inhibitors of these proteins, i.e., tissue inhibitors of MMP (TIMP-1 and TIMP-2) increased. Two major compounds from EEAC codycepin and zhankuic acid A alone and together inhibited MMP-9 and MMP-2 expressions. Further investigation revealed that A. cinnamomea suppressed the phosphorylation of p38, and JNK1/2. A. cinnamomea also suppressed the expressions of PI3K and phosphorylation of AKT. This is the first report confirming the anti-migration activity of this potentially beneficial mushroom against human lung adenocarcinoma CL1-0.

Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status - Corrected Proof

Ching Hui Chen, Linda A. deGraffenried — 2012-04-05

Abstract: Background: Many traditional Chinese medicines target the treatment of inflammation which is emerging to be a critical component to cancer development and progression. The key aromatic compound in star anise anethole has demonstrated both anti and pro-cancerous effects depending on the estrogen receptor statuses in individual cell lines. In this study, we investigated the effect of anethole on the physiological responses and specific apoptotic pathways in human breast cancer MCF-7 and MDA-MB-231 cells that are well-characterized to represent estrogen receptor (ER) positivity and its counterpart in breast cancer respectively. How anethole affects the activity and expression of apoptotic caspases, the function of transcriptional factor NF-kB and the relative influence ER exerts on these events are areas of significant research relevance and results may impact the pharmaceutical development of anethole and its use as dietary supplementation.Methodology/principal findings: Initial analyses of physiological responses using MTT and colony formation assays had demonstrated a preferentially suppression of cell survival to cell proliferation in both ER+ and ER− cells when cells were exposed to anethole. Western blot analysis has demonstrated induction of caspase 9 and PARP1/2 cleavage in parallel with elevated expression of c-FLIP (s) and p53. The transcriptional activity of NF-kB, an upstream activator of p53 is suppressed in both cell lines when treated with anethole.Conclusions: In conclusion, anethole in an ER independent manner suppresses cell survival and induces apoptotic events in MCF-7 and MDA-MB-231 at an optimal concentration of 1×10−3M. In search of alternative compounds for therapeutic development, this study has demonstrated that anethole may be viable as an anti-cancer agent through the modulation of apoptosis, cell survival and proliferation in breast cancer cells.

Phase II trial on the effects of Silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder - Corrected Proof

B. Uehleke, S. Schaper, A. Dienel, S. Schlaefke, R. Stange — 2012-04-04

Abstract: Silexan, a novel lavender oil preparation for oral use, has been authorized in Germany for the treatment of states of restlessness during anxious mood. An open-label, exploratory trial was performed to assess the potential of the medicinal product in the treatment of restlessness caused by anxiety as related to several disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R), von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey Questionnaire (SF-36), and a sleep diary.50 male and female patients with neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or somatization disorder (F45.0, F45.1) were included to receive 1×80mg/day Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%, resp. 62% showed improvements during treatment (p<0.001). For all patients, mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as compared to baseline, (p<0.001), while the SF-36 Mental Health Score increased by 48.2% (p<0.001). Waking-up frequency (p=0.002), Waking-up duration (p<0.001) and morning tiredness (p=0.005) were reduced, while efficiency of sleep (p=0.018) and mood (p=0.03) improved. Patients suffering from neurasthenia or PSD showed comparable improvements with most outcomes.The results in this trial justify to further investigate Silexan in disorders with accompanying restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly gastrointestinal complaints, were judged as mild or moderate.

Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p21 - Corrected Proof

2012-03-30

Abstract: Triptolide, a diterpene triepoxide compound extracted from the traditional Chinese medicine herb Tripterygium wilfordii Hook F., is a potential cancer chemotherapeutic for tumors. However, the mechanism of anti-proliferative mechanism of triptolide in colon cancer cells is not entirely clear. Triptolide markedly inhibited HT29 and SW480 cells proliferation in a dose- and time-dependent manner. Triptolide decreased ERK and AKT phosphorylation, and GABPα expression in colon cancer cells. Beta-catenin expression and phosphorylation were not altered by incubation of triptolide. However, we found that triptolide repressed expression of LEF/TCF. Although it did not significantly affect cells apoptosis, triptolide induced G1 phase arrest dose-dependently. Further detection for the expression of cell cycle-related proteins suggesting that triptolide stimulate expression of p21 and repress cyclin A1. Increased p21 binded to CDK4/CDK6, therefore blocked function of CDK4/CDK6, and subsequently contribute to the G1 arrest. These data suggested that triptolide is a potential agent for treatment of colon cancer, and its anti-proliferation effect mainly occur through G1 phase arrest.

Acetylcholinesterase inhibition in cognition-relevant brain areas of mice treated with a nootropic Amazonian herbal (Marapuama) - Corrected Proof

2010-09-16

Abstract: The goal of acetylcholinesterase inhibitors (AChEIs) used to treat Alzheimer's patients is an improvement in cholinergic transmission. While currently available AChEIs have limited success, a huge impediment to the development of newer ones is access to the relevant brain areas. Promnesic, anti-amnesic and AChEI properties were identified in a standardized ethanol extract from Ptychopetalum olacoides (POEE), a medicinal plant favored by the elderly in Amazon communities. The purpose of this study was to provide conclusive evidence that orally given POEE induces AChE inhibition in brain areas relevant to cognition. Histochemistry experiments confirmed that the anticholinesterase compound(s) present in POEE are orally bioavailable, inducing meaningful AChE inhibition in the hippocampus CA1 (∼33%) and CA3 (∼20%), and striatum (∼17%). Ellman's colorimetric analysis revealed that G1 and G4 AChE isoforms activities were markedly inhibited (66 and 72%, respectively) in hippocampus and frontal cortex (50 and 63%, respectively), while G4 appeared to be selectively inhibited (72%) in the striatum. Western blotting showed that POEE did not induce significant changes in the AChE immunocontent suggesting that its synthesis is not extensively modified. This study provides definitive proof of meaningful anticholinesterase activity compatible with the observed promnesic and anti-amnesic effects of POEE in mice, reaffirming the potential of this extract for treating neurodegenerative conditions where a hypofunctioning cholinergic neurotransmission is prominent. Adequate assessment of the safety and efficacy of this extract and/or its isolated active compound(s) are warranted.

WITHDRAWN: Apoptosis of human tumor cell lines by a lectin (futalin) of Artocarpus incisa seeds - Corrected Proof

Maria do Carmo Avides, J.A. Teixeira, A. Vicente — 2010-01-22

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

WITHDRAWN: Hypoglycemic and hypolipidemic effect of a novel Gymnemic triacetate on STZ-induced diabetic rats - Corrected Proof

P. Daisy, J. Eliza, K.A. Mohamed Farook — 2009-09-14

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

WITHDRAWN: Monitoring herbal safety: Current debate and resources: Symposium report: Pharmacovigilance of herbal medicines: Current state and future direction, London, 24–26 April 2006 - Corrected Proof

Simon Mills — 2009-07-24

WITHDRAWN: New Community herbal monographs - Corrected Proof

Barbara Steinhoff — 2009-07-24

WITHDRAWN: New Community herbal monographs - Corrected Proof

Barbara Steinhoff — 2009-07-24

WITHDRAWN: Awards 2008 of the Society for Medicinal Plant Research (GA) - Corrected Proof

H. Wagner — 2009-07-24

WITHDRAWN: EDITORIAL - Corrected Proof

Barbara Steinhoff — 2009-07-24