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Purpose : To define the actions of boron on normal neurophysiology and glioblastoma growth. Materials and Methods : PubMed and other relevant databases were searched. Results : Discovery of novel boron compounds in treatment of glioblastoma is being actively investigated, but the majority of such studies is focused on the synthesis of boron compounds as sensitizers to Boron Neutron Capture Therapy (BNCT). Nonetheless, the translational functionality of boron compounds is not limited to BNCT as many boron compounds possess direct tumoricidal activity and there is substantial evidence that certain boron compounds can cross the blood-brain barrier. Moreover, boron-containing compounds interfere with several tumorigenic pathways including intratumoral IGF-I levels, molybdenum Fe-S containing flavin hydroxylases, glycolysis, Transient Receptor Potential (TRP) and Store Operated Calcium Entry (SOCE) channels. Conclusions : Boron compounds deserve to be studied further in treatment of systemic cancers and glioblastoma due to their versatile antineoplastic functions.

Background: There is currently insufficient evidence for the clinical effectiveness and cost-effectiveness of psychological therapies for post-stroke depression., Objective: To evaluate the feasibility of undertaking a definitive trial to evaluate the clinical effectiveness and cost-effectiveness of behavioural activation (BA) compared with usual stroke care for treating post-stroke depression., Design: Parallel-group, feasibility, multicentre, randomised controlled trial with nested qualitative research and a health economic evaluation., Setting: Acute and community stroke services in three sites in England., Participants: Community-dwelling adults 3 months to 5 years post stroke who are depressed, as determined by the Patient Health Questionnaire-9 (PHQ-9) or the Visual Analogue Mood Scales 'Sad' item. Exclusions: patients who are blind and/or deaf, have dementia, are unable to communicate in English, do not have mental capacity to consent, are receiving treatment for depression at the time of stroke onset or are currently receiving psychological intervention., Randomisation and Blinding: Participants were randomised (1 : 1 ratio) to BA or usual stroke care. Randomisation was conducted using a computer-generated list with random permuted blocks of varying sizes, stratified by site. Participants and therapists were aware of the allocation, but outcome assessors were blind., Interventions: The intervention arm received up to 15 sessions of BA over 4 months. BA aims to improve mood by increasing people's level of enjoyable or valued activities. The control arm received usual care only., Main Outcome Measures: Primary feasibility outcomes concerned feasibility of recruitment to the main trial, acceptability of research procedures and measures, appropriateness of baseline and outcome measures, retention of participants and potential value of conducting the definitive trial. Secondary feasibility outcomes concerned the delivery of the intervention. The primary clinical outcome 6 months post randomisation was the PHQ-9. Secondary clinical outcomes were Stroke Aphasic Depression Questionnaire - Hospital version, Nottingham Leisure Questionnaire, Nottingham Extended Activities of Daily Living, Carer Strain Index, EuroQol-5 Dimensions, five-level version and health-care resource use questionnaire., Results: Forty-eight participants were recruited in 27 centre-months of recruitment, at a recruitment rate of 1.8 participants per centre per month. The 25 participants randomised to receive BA attended a mean of 8.5 therapy sessions [standard deviation (SD) 4.4 therapy sessions]; 23 participants were allocated to usual care. Outcome assessments were completed by 39 (81%) participants (BA, n  = 18; usual care, n  = 21). Mean PHQ-9 scores at 6-month follow-up were 10.1 points (SD 6.9 points) and 14.4 points (SD 5.1 points) in the BA and control groups, respectively, a difference of -3.8 (95% confidence interval -6.9 to -0.6) after adjusting for baseline PHQ-9 score and centre, representing a reduction in depression in the BA arm. Therapy was delivered as intended. BA was acceptable to participants, carers and therapists. Value-of-information analysis indicates that the benefits of conducting a definitive trial would be likely to outweigh the costs. It is estimated that a sample size of between 580 and 623 participants would be needed for a definitive trial., Limitations: Target recruitment was not achieved, although we identified methods to improve recruitment., Conclusions: The Behavioural Activation Therapy for Depression after Stroke trial was feasible with regard to the majority of outcomes. The outstanding issue is whether or not a sufficient number of participants could be recruited within a reasonable time frame for a definitive trial. Future work is required to identify whether or not there are sufficient sites that are able to deliver the services required for a definitive trial., Trial Registration: Current Controlled Trials ISRCTN12715175., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 47. See the NIHR Journals Library website for further project information., Competing Interests: Shirley A Thomas and Avril ER Drummond report grants from the National Institute for Health Research (NIHR) and the Stroke Association outside the submitted work. Rebecca L Palmer is an author of the Consent Support Tool, which was piloted in the work and is discussed in the report. Roshan das Nair is a member of the NIHR Health Services and Delivery Research Board. Nicholas R Latimer is supported by the NIHR (NIHR Post Doctoral Fellowship PDF-2015-08-022). Stephen J Walters is a member of the NIHR Health Technology Assessment (HTA) Clinical Trials Board and the NIHR HTA Funding Boards Policy Group; he also reports grants from the NIHR HTA programme during the conduct of the study, personal fees from royalties, research grants from the NIHR and the Medical Research Council, personal fees from external examining fees and book royalties outside the submitted work. Cindy L Cooper is a member of the NIHR Clinical Trials Unit Standing Advisory Committee.

Noscapine is a phthalide isoquinoline alkaloid that easily traverses the blood brain barrier and has been used for years as an antitussive agent with high safety. Despite binding opioid receptors, noscapine lacks significant hypnotic and euphoric effects rendering it safe in terms of addictive potential. In 1954, Hans Lettré first described noscapine as a mitotic poison. The drug was later tested for cancer treatment in the early 1960's, yet no effect was observed likely as a result of its short biological half-life and limited water solubility. Since 1998, it has regained interest thanks to studies from Emory University, which showed its anticancer activity in animal models with negligible toxicity. In contrast to other microtubule-inhibitors, noscapine does not affect the total intracellular tubulin polymer mass. Instead, it forces the microtubules to spend an increased amount of time in a paused state leading to arrest in mitosis and subsequently inducing mitotic slippage/mitotic catastrophe/apoptosis. In experimental models, noscapine does not induce peripheral neuropathy, which is common with other microtubule inhibitors. Noscapine also inhibits tumor growth and enhances cancer chemosensitivity via selective blockage of NF-κB, an important transcription factor in glioblastoma pathogenesis. Due to their anticancer activities and high penetration through the blood-brain barrier, noscapine analogues strongly deserve further study in various animal models of glioblastoma as potential candidates for future patient therapy.

Objective: To investigate Phosphorylated adenosine monophosphate activated protein kinase (AMPK) levels in healthy pregnant women and pregnant women with preeclampsia (PE)., Methods: Twenty-eight women with mild-PE, 22 with severe-PE, and 30 normotensive controls were included in this cross-sectional study. The serum AMPK levels of these patients were analyzed. The patients were followed up to delivery., Results: No statistically significant difference was found between the groups for age, gravida, parity, and gestational age at the time the blood samples were obtained (p > .05). No significant difference between the group with mild-PE and the control group was found, while in the severe-PE group, serum AMPK levels were significantly higher relative to both the mild-PE and control groups (p < .001 and p < .001, respectively). No correlation was detected between serum AMPK levels and age, body mass index (BMI), and gestational age at the time the blood samples were collected. A negative correlation was found between AMPK levels and gestational week and birthweight at delivery, while a positive correlation was detected between systolic and diastolic blood pressures and AMPK levels., Conclusions: Serum AMPK was higher in patients with severe-PE compared with healthy pregnant women and patients with PE without severe features so it might be a new biomarker for the prediction of disease and its severity.

Chloroform, ethyl acetate and methanol extracts from the aerial parts of Ferula caspica M. Bieb. were tested for their antioxidant capacities by CUPRAC, ABTS, FRAP, Folin-Ciocalteu and aluminum chloride methods and for antimicrobial activities by the broth microdilution method. Chloroform and ethyl acetate extracts showed the highest antioxidant capacity and antimicrobial activity. Three known sesquiterpene derivatives; 1-(2',4'-dihydroxyphenyl)-3,7,11-trimethyl-3-vinyl-6(E),10-dodecadien-1-one ( 1 ), 2,3-dihydro-7-hydroxy-2,3-dimethyl-2-[4',8'-dimethyl-3',7'-nonadienyl]-furo[3,2,c]coumarin ( 2 ), 2,3-dihydro-7-hydroxy-2,3-dimethyl-3-[4',8'-dimethyl-3',7'-nonadienyl]-furo[3,2,c]coumarin( 3 ); phenylpropanoid; laserine/2-epilaserine ( 4/5 ) and steroid mixtures; stigmasterol and β -sitosterol ( 6/7 ) were isolated from chloroform extract; three known flavonoids; kaempferol-3- O - β -glucopyranoside ( 8 ), kaempferol-3- O - α -rhamnopyranoside ( 9 ), quercetin-3- O - β -glucopyranoside ( 10 ), and one benzoic acid derivative; 2,4-dihydroxybenzoic acid ( 11 ) were isolated from the ethyl acetate extract. The structures were elucidated by spectroscopic methods.

Objective: To determine the feasibility of conducting a trial of a pre-surgical psychological intervention on pain, function, and mood in people with knee osteoarthritis listed for total knee arthroplasty., Design: Multi-centre, mixed-methods feasibility randomized controlled trial of intervention plus usual care versus usual care., Setting: Participants' homes or hospital., Participants: Patients with knee osteoarthritis listed for total knee arthroplasty and score >7 on either subscales of Hospital Anxiety and Depression Scale., Intervention: Up-to 10 sessions of psychological intervention (based on cognitive behavioural therapy)., Main Measures: Feasibility outcomes (recruitment and retention rates, acceptability of trial procedures and intervention, completion of outcome measures), and standardized questionnaires assessing pain, function, and mood at baseline, and four and six months post-randomisation., Results: Of 222 people screened, 81 did not meet inclusion criteria, 64 did not wish to participate, 26 were excluded for other reasons, and 51 were randomized. A total of 30 completed 4-month outcomes and 25 completed 6-month outcomes. Modal number of intervention sessions completed was three (range 2-8). At 6-month follow-up, mood, pain, and physical function scores were consistent with clinically important benefits from intervention, with effect sizes ranging from small ( d = 0.005) to moderate ( d = 0.74), and significant differences in physical function between intervention and usual care groups ( d = 1.16). Feedback interviews suggested that participants understood the rationale for the study, found the information provided adequate, the measures comprehensive, and the intervention acceptable., Conclusion: A definitive trial is feasible, with a total sample size of 444 people. Pain is a suitable primary outcome, but best assessed 6 and 12 months post-surgery.

Flavonoids are naturally occurring phenolic compounds named as 2-phenyl-1-benzopyran- 4-one and classified into several subclasses according to their basic chemical structures such as flavones, flavonols, flavanones, flavanonols, and flavanols. Among them, flavonols (3-hydroxyflavone), containing a 3-hydroxyl group in association with its 4-keto group and double bond between 2- and 3- carbon atoms, have the best electron conjugated skeleton in flavonoid family, providing several resonance structures and chelating ability, through which various pharmacological activities such as antiviral, antitumour, anti-inflammatory, anticholinesterase, cytotoxicity and particularly high antioxidant activity are demonstrated. They prevent generation of free radicals and are used as food preservatives. Their strong electron conjugation provides them with fluorescent property, which make them used as imaging agents for therapeutic purpose., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Oleanolic acid (OA) is a known natural compound with many important biological activities. Thirteen oleanolic acid derivatives linked at C-3 and C-28 were synthesized and their structures were confirmed by 1H- and 13C NMR and mass spectral analyses. Among them, compounds 4, 6, 8-10, 12, 13 were synthesized for the first time. They were evaluated for their cytotoxic activity. They showed proliferative effect at low concentrations while cytotoxic effect was observed at high concentrations in a dose dependent manner., Methods: We have first synthesized compounds 1 and 2 from the reaction of methyl iodide and OA. Compound 1 was reduced with LiAlH4 to give compound 3, and compound 2 gave compound 9 with MOMBr as a new compound. The compound 10 was then obtained from the reduction of compound 9 with LiAlH4 as a new oleanolic acid derivative. A diol derivative 11 was synthesized from OA and LiAlH4 at the room temperature. Compound 4 was obtained from the reaction of compound 3 with CBr4 as a new analogue of OA, and the reduction of compound 4 afforded compound 5 as a known product. In addition, we synthesized compounds 6-8 from compound 3 using MsCl, MeI and p-nitrobenzoyl chloride, respectively, in good yields. Compounds 6 and 8 are new analogues of OA. The new compounds 12 and 13 were also synthesized starting from OA using with MOMBr and TBDMSiCl as the reagents. The all synthesized compounds were purified by using column chromatography and/or crystallization., Results: In the present study, thirteen OA derivatives linked at C-28 and (or) C-3 were synthesized and evaluated for their cytotoxic activity on 3T3 cell lines which are the standard fibroblast cell lines, derived from Swiss albino mouse embryo tissue. 3T3 cell viability was observed at low concentrations of the tested triterpenoids while they displayed anti-proliferative effect at higher concentrations., Conclusion: Oleanolic acid 28-methyl ester (2) showed fairly different behavior from all the other compounds tested and found to be the least cytotoxic compound. However, at 200 µM concentration, it exhibited the same cytotoxicity with compounds 3, 9 and 10 around 58-59%. Among the tested 13 compounds, 7 exhibited the most drastic decline for the viability from 12,5 µM to 25 µM concentration. Compound 6 displayed the most cytotoxic effect, almost in all concentrations, particularly at 6.25 and 25 µM concentrations while the highest cytotoxic effect at 50 µM was observed for compound 11 among all the tested triterpenoids. As a result, all the tested OA derivatives showed proliferative effect at 1,56 µM although no proliferative effect was observed for OA. Moreover, OA exhibited higher cytotoxic effect than its derivatives, particularly at higher concentrations (50, 100, 200 µM) with an exception for compound 11. Because, the latter showed highest proliferative effect at lowest concentration, and highest anti-proliferative effect at highest concentration which surpassed all the OA derivatives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Self-assembly systems (SAS) mainly consist of micelles, and liposomes are the classes of Nano Drug Delivery Systems with superior properties compared to traditional therapeutics in targeting cancer tumors. All commercially available nano-formulations of chemotherapeutics currently consist of SAS. According to our knowledge, a specific toxicity comparison based on material differences has not yet been performed. The purpose of this study was to evaluate and compare the toxicity of two SAS consisting of Sterically Stabilized Micelles (SSM) made of a lipid-based amphiphilic distearoyl-sn-glycero-phosphatidylethanolamine-polyethylene glycol (PEG)-2000 and a polymeric micelle (PM) consisting of Y-shape amphiphilic block copolymer, synthesized using poly ε-caprolactone and PEG. The mechanism of cytotoxicity and genotoxicity of micelles on L-929 healthy mouse fibroblast cells was assessed using Sulforhodamine-B, WST-1, Acridine Orange/Ethidium Bromide and alkaline single-cell gel electrophoresis assays. Results showed that SSM in conc. of 40 mg/mL shows very low cytotoxicity at the end of 24, 48 and 72 h. The DNA damage caused by SSM was much lower than PM while the latter one showed significant toxicity by causing apoptosis with the ED50 value of 3 mg/mL. While the DNA damage caused by SSM was ignorable, some DNA chain breaks were detected on cells treated with PM., Competing Interests: The authors declare no conflict of interest.

Background: In this study a combination of Mometasone Furoate (MF)+Levofloxacin hemihydrate (LH)+Retinyl palmitate (RP) with an in situ gel-forming delivery system was evaluated at different stages of nasal mucosal damage repair in a rabbit maxillary sinus model., Methods: In this study, 28 rabbits were included and assigned randomly to four groups. In all rabbits, a standard ostium was opened in the medial wall of the maxillary sinus by using a drill. Two different subsequently prepared gels with an in situ gel-forming delivery system were used. Of these 14 nasal cavities, combination 1 (active combination) was applied daily to 5, combination 2 (placebo) to 5, while 4 did not receive any pharmaceutical treatment. The diameter of the ostium was measured. Histopathological assessment was performed., Results: After 2, 3 and 4 weeks, the ostium diameter was significantly wider in the group where gel 1 had been applied compared to both the placebo group and control group. In the group treated with gel 1, after 2, 3 and 4 weeks the presence of superficial cilia was significantly greater, surface epithelium significantly less. In the 4th week, histologic scores for fibroblastic proliferation and vascular proliferation in the group treated with gel 1 were better than in either the control group or the placebo group. With gel 1, chronic inflammation parameters were also significantly lower than in the other groups., Conclusion: The MF+LH+RP mixture with an in situ gel-forming nasal delivery system applied for wound healing after FESS prevents the formation of stenosis and is favorable for proper wound healing., (Copyright © 2017. Published by Elsevier Masson SAS.)

Context: Origanum (Lamiaceae) has been used in food and pharmaceutical industries., Objective: Isolation and identification of bioactive compounds from Origanum rotundifolium Boiss. and investigation of their antiproliferative and antioxidant activities., Materials and Methods: The aerial part of O. rotundifolium was dried and powdered (1.0 kg ±2.0 g) then extracted with hexane, ethyl acetate, methanol and water. Solvent (3 × 1 L) was used for each extraction for a week at room temperature. The aqueous extract was partitioned with ethyl acetate (3 × 1 L) to yield the water/EtOAc extract subjected to chromatography to isolate the active compounds. The structures of isolated compounds were elucidated by 1 D, 2 D NMR and LC-TOF/MS., Results: Apigenin (1), ferulic acid (2), vitexin (3), caprolactam (4), rosmarinic acid (5), and globoidnan A (6) were isolated and identified. Globoidnan A (6), vitexin (3), and rosmarinic acid (5) revealed the excellent DPPH • scavenging effect with IC 50 values of 22.4, 31.4, 47.2 μM, respectively. Vitexin (3) (IC 50 3.6), globoidnan A (6) (IC 50 4.6), apigenin (1) (IC 50 8.9) and ferulic acid (2) exhibited more ABTS •+ activity than standard Trolox (IC 50 13.8 μg/mL). Vitexin (3) revealed the most antiproliferative activity against HeLa, HT29, C6 and Vero cells lines with IC 50 values of 35.6, 32.5, 41.6, 46.7 (μM), respectively., Discussion and Conclusion: Globoidnan A (6) has the most antioxidant effects on all assays. This has to do with the chemical structure of the compound bearing the acidic protons. Vitexin (3) could be a promising anticancer agent.

Introduction: Salvia, an important and widely available member of Lamiaceae family. Although comparative analysis on secondary metabolites in several Salvia species from Turkey has been reported, their hallucinogenic chemicals have not been screened thoroughly., Objective: This study provides LC-MS/MS analysis of 40 Salvia species for screening their psychoactive constituents of salvinorin A and salvinorin B. 5S-rRNA gene non-coding region of Salvia plants was sequenced, aligned and compared with that sequence of Salvia divinorum plant., Methodology: Targeted molecules of salvinorin A and salvinorin B were quantified, using LC-MS/MS, from all aerial parts of 40 Salvia species, collected from different parts of Turkey. Regions of 5S-rRNA gene from different species were amplified by polymerase chain reaction and DNA sequences were aligned with Salvia divinorum DNA sequences., Results: Very few of the Salvia species (S. recognita, S. cryptantha and S. glutinosa) contained relatively high levels of salvinorin A (212.86 ± 20.46 μg/g, 51.50 ± 4.95 μg/g and 38.92 ± 3.74 μg/g, respectively). Salvinorin B was also found in Salvia species of S. potentillifolia, S. adenocaulon and S. cryptantha as 2351.99 ± 232.22 μg/g, 768.78 ± 75.90 μg/g and 402.24 ± 39.71 μg/g, respectively. The sequences of 5S-rRNA gene of 40 different Salvia species were presented and it was found that none of the Salvia species in Turkey had similar DNA sequence to Salvia divinorum plant., Conclusion: This is the first report of screening 40 Salvia species in Turkey according to their psychoactive constituents, salvinorin A and salvinorin B and their genomic structures. It is possible that some of these Salvia species may exhibit some psycho activity. Thus, they need to be screened further. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Flavones, are a class of naturally occuring polyphenolic compounds which have 2-phenylchromen-4-one structure. Various studies showed that flavones have several pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antitumour and antiallergic. In the present study, 3-hydroxyflavones also called flavonols, posessing 4'-dialkylamino moiety were synthesized, and their antioxidant and anticholinesterase activities were investigated by comparison with unmodified 3-hydroxflavone., Method: For investigation of antioxidant potential, radical scavenging assays (DPPH•, ABTS+&#95;, O2.-) were used along with CUPRAC and lipid peroxidation inhibitory assays, as well as anticholinesterase activity by Ellman method., Results: The best results were obtained for 4'-N,N-dimethyl flavonol (1) in both antioxidant and anticholinesterase activity tests, possibly due to its least steric hinderance effect. It exhibited remarkable DPPH free radical scavenging activity (2.43±0,09 μg/mL) competing with a standard compound quercetin (2.10±0,10 μg/mL). Moreover, the other tested flavonols also showed high antioxidant activities. Compounds 5 and 6 exhibited close IC50 values to those of compound 1., Conclusion: Antioxidant activity test results were found to be well correlated with anticholinesterase activity test results indicating possible role of antioxidant compounds in the treatment of Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: The lack of adequate conceptualisation and operationalisation of quality of life (QoL) limits the ability to have a consistent body of evidence to improve QoL research and practice in informal caregiving for people with multiple sclerosis (MS). Thus, we conducted a meta-synthesis of qualitative research to improve the conceptual understanding of the experiences of MS carers and to identify factors that affect carers' QoL., Design: Systematic searches of five electronic databases yielded 17 qualitative studies which were synthesised using the principles of meta-ethnography., Results: The synthesis resulted in nine inter-linking themes: Changes and losses; challenges revolving around MS; caregiving demands; burden of care; future concerns; external stressors; experiences of support; strategies used in managing the caregiving role; and motivating factors. Our findings suggest that MS carers can have both positive and negative experiences which may bring challenges and rewards to the carers., Conclusion: We present a proposed QoL model for MS caregiving which can be used to inform the development of interventions for MS carers to improve their QoL. However, further empirical research is needed to examine the utility of this model and to explore the concept of QoL in MS carers in more detail.

We study the high-temperature behavior of an intermediate-statistics fermionic gas model whose quantum statistical properties enable us to effectively deduce the details about both the interaction among deformed (quasi)particles and their anyonic behavior. Starting with a deformed fermionic grand partition function, we calculate, in the thermodynamical limit, several thermostatistical functions of the model such as the internal energy and the entropy by means of a formalism of the fermionic q calculus. For high temperatures, a virial expansion of the equation of state for the system is obtained in two and three dimensions and the first five virial coefficients are derived in terms of the model deformation parameter q. From the results obtained by the effect of fermionic deformation, it is found that the model parameter q interpolates completely between bosonlike and fermionic systems via the behaviors of the third and fifth virial coefficients in both two and three spatial dimensions and in addition it characterizes effectively the interaction among quasifermions. Our results reveal that the present deformed (quasi)fermion model could be very efficient and effective in accounting for the nonlinear behaviors in interacting composite particle systems.

Context: In Turkey, Veronica species (Plantaginaceae) have been used as a diuretic and for wound healing in traditional medicine., Objective: To examine the fatty acid and essential oil profiles, the antioxidant, anticholinesterase, antimicrobial, and DNA damage effects of Veronica thymoides P.H. Davis subsp. pseudocinerea M.A. Fischer as a potential source of natural active compounds., Materials and Methods: GC/MS was used to analyze essential oil and fatty acid obtained from whole plant. The antioxidant activity was evaluated by the β-carotene-linoleic acid test system, DPPH-free and ABTS cation radicals scavenging, and cupric reducing antioxidant capacity assays. The anticholinesterase and antimicrobial activities were determined by Ellman and broth macrodillution methods, respectively. The effect of the methanol extract on DNA cleavage was investigated., Results: Hexatriacontene (21.0%) was found to be the main constituent in essential oil, and linoleic acid (25.2%) and palmitic acid (20.6%) in fatty acid. Methanol extract demonstrated the best IC50 values in lipid peroxidation (49.81 ± 0.31 µg/ml) and DPPH-free radical scavenging activity (15.32 ± 0.17 µg/ml). Methanol and water extracts possessed strong ABTS cation radical scavenging activity with IC50 values 9.15 ± 0.28 and 8.90 ± 0.1  µg/ml, respectively. The acetone extract exhibited moderate butyrylcholinesterase inhibitory activity. The highest antimicrobial activity was determined in methanol extract against Escherichia coli with 31.25 µg/ml MIC value. Inhibition of methanol extract on plasmid DNA cleavage by OH radicals was found to be 93.32% at 500 µg/ml., Conclusion: The methanol extract having strong antioxidant and DNA damage effects could be investigated phytochemically to find natural active compounds.

Trifolium nigrescens was researched for its chemical constituents for the first time. Bioassay-guided isolation of the EtOAc extract from the leaves of T. nigrescens resulted in the purification of a new biflavone, 4''',5,5″,7,7″-pentahydroxy-3',3'''-dimethoxy-3-O-β-d-glucosyl-3″,4'-O-biflavone (1) along with eleven known compounds consisting of three phenolics (2-4), and eight flavonoid glycosides (5-12). Their structures were determined by extensive 1D and 2D NMR, and MS data analyses. The isolated compounds were evaluated for their antioxidant activity and inhibitory activity on mushroom tyrosinase. Highly potent inhibitions were found by compounds 7 (IC50 = 0.38 mM), 8 (IC50 = 0.19 mM), and 12 (IC50 = 0.26 mM) when compared with standard tyrosinase inhibitors kojic acid (IC50 = 0.67 mM) and l-mimosine (IC50 = 0.64 mM). The antioxidative effect of the isolated compounds and the extracts were determined by using β-carotene-linoleic acid, DPPH(•) scavenging, ABTS(+•) scavenging, superoxide scavenging, and CUPRAC assays. The experimental findings indicated that all the compounds demonstrated activity in all antioxidant activity tests employed except for the compounds 2-6. Compounds 2-6 showed moderate activity only in ABTS(+•) scavenging assay. The new compound 1 exhibited better activity than standard α-tocopherol in DPPH(•) scavenging, and ABTS(+•) scavenging assays. The results show that T. nigrescens can be regarded as a potential source of antioxidant compounds and tyrosinase inhibitors of significance in both the pharmaceutical and food industries.

Two bischromones, 3,3'-dimethoxy-2'-oxychromone (1), 3,3'-dihydroxy-2,2'-oxychromone (2) and a biflavone, 5,7,4',5″,3'",4″″-hexahydroxy-3″-O-β-glucosyl-3',7″-O-biflavone (3) have been isolated from whole plant of Trifolium echinatum Bieb. together with five known flavonoids. The structures of the compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds were investigated for their antioxidant activity and tyrosinase inhibitory activity. Highly potent inhibition was found for compounds 1 (IC50=0.41 mM), 5 (IC50=0.47 mM) and 8 (IC50=0.45 mM) compared to those of standard tyrosinase inhibitors kojic acid (IC50=0.67 mM) and l-mimosine (IC50=0.64 mM). The antioxidative effect of the extracts was determined by using β-carotene-linoleic acid, DPPH scavenging, ABTS(+) scavenging, and CUPRAC assays. The experimental findings indicated that the compounds 2 and 8 were found to be active in radical scavenging and CUPRAC assays., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Aims: Ankaferd Blood Stopper (ABS) is a herbal extract obtained from five different plants. It has a therapeutic potential for the management of external hemorrhage and controlling gastrointestinal bleeding. However, ABS's effects are not unknown on gastrointestinal systems. The aim of this study was to assess the effect of short- and long-term systemic exposure and gastrointestinal safety following the oral administration of high-dose ABS in rats., Methods: Eighteen healthy adult male rats were included into the study. The rats were divided into 4 groups: group A was fed with high dose ABS (2ml/Kg) for one week, group B for one month, group C for three months and group D's diet did not contain any ABS. On termination of the ABS treatment, the gastrointestinal system from the esophagus to the anus and the liver were surgically removed and histological investigated., Results: During the study period, there was no mortality; signs of intoxication in any of the studied groups. No gastrointestinal tissue fibrosis, dysplasia, or metaplasia was detectable in any of the groups. The stomach had a normal morphology in all groups. However, the other gastrointestinal tract sections showed mucosal inflammation, goblet cell decrements, and intra-epithelial lymphocyte infiltration. The most common changes were mucosal inflammation in all rats in group B and C. Frequency of inflammation was greater in groups B and C in comparison to group A (P= 0.001). Loss of goblet cell and intra-epithelial lymphocyte infiltration were not significantly different between groups A and B (P=0.308 and P=0.189, respectively). However, there was significantly higher intra-epithelial lymphocyte infiltration in group C than in group A (P=0.04). Histopathological examination of the liver showed no inflammation, fibrosis, bile duct destruction or proliferation in any of the groups. However, each groups revealed vascular dilatation and erythrocyte accumulation at the sinusoidal structures of the liver., Conclusions: ABS seems to be a safe agent and it can be used for hemorrhage originated from gastric lesions. Further work needs to be done to establish whether ABS leads to be used to stop gastrointestinal bleeding.

A new sterol glucoside, (24R)-5 alpha-stigmast-9-(11)-en-3beta-D-glucopyranoside (1) has been isolated from a methanol extract of the red alga Gracilaria verrucosa, while cholesterol and (Z)-9-hexadecenoic acid (palmitoleic acid) have been isolated from a dichloromethane-acetone extract of the same alga. Additionally, an oily fraction of a dichloromethane-acetone extract has been investigated by gas chromatography/mass spectrometry (GC/MS). The main components in the oily fraction were heneicosanoic acid (49.8%), (Z)-9-octadecenoic acid (15.8%), and 15-tetracosenoic acid (15.6%) in addition to a few hydrocarbons, simple aromatics and a new compound, namely 3,4-dimethyl-5-carboxyclic acid-1-oxacyclopent-3-en-2-one. The structures of the isolated compounds have been elucidated by spectroscopic methods.

A new phenolic ester 2-( p-hydroxyphenyl)ethyl eicosaheptanoic acid ester (1) and a known one hexacosylferulate (2) were isolated from the acetone extract of Salvia microphylla. In addition, two sesquiterpenes beta-eudesmol (3) and 8alpha-hydroxy-beta-eudesmol (4), a diterpene carnosic acid 12-methyl ether (12-methoxycarnosic acid) (5), three triterpenes erithrodiol 3-acetate, oleanolic acid, lupeol and beta-sitosterol were obtained as known compounds from this plant extract. The structures of the isolated compounds were elucidated by spectroscopic methods, including one- and two- dimensional 1H- and 13C-NMR and MS spectroscopies. The selected compounds were tested for antimicrobial activity against standard bacterial strains, and only carnosic acid 12-methyl ether showed antimicrobial activity against S. aureus at 78 microg mL(-1).

We report on the synthesis by coupling of a triterpenoid oleanolic acid with 4'-diethylamino-3-hydroxyflavone (FE) to produce an environment-sensitive biomembrane probe with two-band ratiometric response in fluorescence emission. The synthesized compound (probe FOT) was tested in a series of model solvents and demonstrated the response to solvent polarity and intermolecular hydrogen bonding very similar to that of parent probe FE. Meantime when incorporated into lipid bilayer membranes, it showed new features differing in response between lipids of different surface charges as well as between glycerophospholipids and sphingomyelin. We observed that in the conditions of coexistence of rafts and non-raft structures the probe is excluded from the rafts.

From the roots of Saliva caespitosa Montbret and Aucher ex. Bentham a new diterpene 6beta-hydroxyisopimaric acid (1) has been isolated together with four known diterpenes, one new triterpenoid, 3-acetylvergatic acid (2), as well as five known triterpenoids, two steroids and a flavone. The structures of the compounds were established by spectroscopic analyses. The isolated compounds were tested against standard bacterial strains. Only the new diterpene, 6beta-hydroxyisopimaric acid has strong activity (MIC 9 microg/ml) against S. aureus and (MIC 18 microg/ml) against S. epidermidis as well as against B. subtilis (MIC 9 microg/ml).

A simplified hplc system is described for the detection of compounds capable of binding to DNA. Compounds known to interact with DNA were found to invoke a positive response with this system, and the concentration-dependence and sensitivity were determined. When applied to 17 randomly selected plant extracts, five elicited a positive response and, of these, four were subsequently found to be cytotoxic with cultured KB or P-388 cells. As described in a companion paper, one of these extracts (derived from Albizia amara) has been further processed and found to contain a group of structurally-unique macrocyclic alkaloids that demonstrate a variety of biological activities. Therefore, this approach should prove a value in facilitating the identification of plant extracts that contain substances capable of binding to DNA and the subsequent activity-directed fractionation for the procurement of active principles. As a prescreen or monitor, these relatively uncomplicated hplc procedures can be used in laboratories not prepared to perform more complicated or costly bioassay techniques. Thus, the pool of potentially active novel chemical substances to be considered for more advanced testing could be increased.

Investigation of the leaves of Montanoa tomentosa Cerv. ssp. microcephala (Sch.-Bip.) Funk (Compositae) resulted in the isolation of three novel guaianolide sesquiterpenes, montacephalin (1), tomencephalin (2), and 5-hydroxytomencephalin (3), which were shown to be cytotoxic (P-388). The structures of these sesquiterpenes were elucidated through analysis of their spectroscopic characteristics, and complete proton and carbon-13 assignments were made for the new compounds. Also isolated were the known terpenes, beta-amyrin, beta-amyrin acetate, stigmasterol, stigmasterol-3 beta-D-glucoside, (-)-kaur-16-en-19-oic acid, and monoginoic acid.