Antimicrobial evaluation of Tripleurospermum callosum (Boiss. & Heldr.) E. Hossain extracts using in vitro and in vivo Caenorhabditis elegans model against urinary system pathogens.

Tripleurospermum callosum (Boiss. & Heldr.) E. Hossain was recorded in Turkish ethnobotanical data for its use against urinary and respiratory system ailments. Infusion, decoction and 96% ethanol extracts of T. callosum aerial parts were prepared for in vitro antimicrobial activity against urinary system pathogens Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Klebsiella aerogenes ATCC 1348 and Candida albicans ATCC 10231. The non-toxic concentrations of extracts and in vivo antimicrobial assay were performed using C. elegans. The extracts were analysed by Liquid Chromatography Mass Spectrometry (LC-MS/MS) for phytochemical composition. The water extracts were non-toxic at between 5000 and 312 µg/mL, while 96% ethanol extract at 312 µg/mL for C. elegans. The infusion extract showed in vivo anti-infective effect 5000-312 µg/mL against Gram-negative strains. The results indicate a potential role of plant extracts with relatively non-toxic and anti-infective effects against urinary system pathogens.

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches.

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol.

Origanum spp. are used both for culinary purposes and for their biological activities. In this study, commercial Origanum majorana, Origanum minutiflorum, Origanum vulgare, and Origanum onites essential oils and their prominent constituent carvacrol were evaluated for their in vitro and in silico angiotensin-converting enzyme 2 and lipoxygenase enzyme inhibitory potentials. The essential oils were analysed by gas chromatography-flame ionisation detection and gas chromatography-mass spectrometry, where carvacrol was identified as the major component (62 - 81%), confirming the quality. In vitro enzyme inhibition assays were conducted both with the essential oils (20 µg/mL) and with carvacrol (5 µg/mL). The comparative values of angiotensin-converting enzyme 2 percent inhibition for O. majorana, O. minutiflorum, O. vulgare, and O. onites essential oils were determined as 85.5, 79.1, 74.3, and 42.8%, respectively. As a result of the enzyme assays, carvacrol showed 90.7% in vitro angiotensin-converting enzyme 2 inhibitory activity. The in vitro lipoxygenase inhibition of the essential oils (in the same order) was 89.4, 78.9, 81.1, and 73.5%, respectively, where carvacrol showed 74.8% inhibition. In addition, protein-ligand docking and interaction profiling was used to gain structural and mechanistic insights into the angiotensin-converting enzyme 2 and lipoxygenase inhibitory potentials of major Origanum essential oil constituents. The in silico findings agreed with the significant enzyme inhibition activity observed in vitro. Further in vivo studies are suggested to confirm the safety and efficacy of the oils.

Binary Synergistic Combinations of Lavender and Fennel Essential Oils with Amoxicillin.

Microbial resistance is an important problem in modern healthcare systems. In addition to drug resistance, the side effects of current antibiotic applications are also known issues. In this present study, binary combinations of amoxicillin with European Pharmacopoeia quality lavender (Lavandula angustifolia) and fennel (Foeniculum vulgare) essential oils were evaluated against human pathogenic microbial strains. The checkerboard method was used to quantify the efficacy of the essential oils in combination with amoxicillin. As an initial result, remarkable in vitro antimicrobial activity was observed at relatively low amoxicillin concentrations using different oil combinations against Staphylococcus aureus ATCC 6538, Enterococcus faecalis ATCC 29212, Bacillus cereus ATCC 14579, Escherichia coli NRRL B-3008, Salmonella typhi (clinical isolate), respectively. Fractional inhibitory concentrations were calculated and interpreted in terms of addition, synergy, antagonism, or indifferent. A synergistic interaction with the combination F. vulgare essential oil and amoxicillin (fractional inhibitory concentration index = 8.05 × 10-4) was observed against the pathogens E. faecalis and Escherichia coli. Both essential oils together and in combination with amoxicillin showed a synergistic effect with possible future applications.

An Investigation Into the Degree of Sinus Mucosal Delivery of Inhaled Black Cumin Volatile and Peppermint Essential Oils.

The aim of this study was to investigate the quantity of volatile components reaching the sinus mucosa (SM) by inhalation, which is responsible for the therapeutic effect, as a first step toward targeted drug design. In this study, 18 Wistar-Albino female rats with an average weight between 200 and 250 g were used. The rats to be used in the study were randomized: Black cumin (BC) essential oil group (group 1) (n = 6), Peppermint essential oil (PEO) group (group 2) (n = 6), and Control (group 3) (n = 6). Volatile oils were inhaled in group 1 and 2; in the control group volatile oils were not inhaled. In all groups, SM was removed and essential volatile oil composition was determined. In group 1, α-pinene was identified as the principal component in the gas phase from five different glass bottles containing SM. The data obtained were evaluated using the single sample T-test and results show that the α-pinene component in the group of inhaled BC essential oil reached significance (P < .001) when compared with the control group. The active component of the BC essential oil could not be identified as thymoquinone. In group 2, eucalyptol (1,8-cineole) was identified as the principal component in the gas phase from five different glass bottles containing SM. The data obtained were evaluated using the single sample T-test and it was found that the eucalyptol component in the group which inhaled PEO reached statistical significance (P < .001) compared with the control group. In group 3, no volatile oil compounds were detected. We have demonstrated that both oils (BC and peppermint) are delivered to the SM. There is a need for the optimum dose to be clarified by different methods of measurement than those used in the spectrometric data we have obtained. We are convinced that our work will lead to pharmacological, toxicological, and subsequent clinical trials in this area.

Secondary metabolites from Verbascum bugulifolium Lam. and their bioactivities.

Five iridoid glycosides catalpol (1), specioside (2), ajugol (3), ajugoside (4), 8-O-acetylharpagide (5), two phenylethanoid glycosides, verbascoside (6) and glucopyranosyl-(1→Gi-6)-martynoside (7), four flavonoids, luteolin (8), luteolin 7-O-ß-glucopyranoside (9), luteolin 7-O-rutinoside (10), apigenin 7-O-rutinoside (11), quercetin 3-O-rutinoside (12) and ß-sitosterol (13) were isolated from the aerial parts of Verbascum bugulifolium Lam. for the first time. Their structures were elucidated by NMR and MS experiments. The extracts, and the isolates were evaluated for their in vitro antioxidant (DPPH•, ABTS• and CUPRAC), anti-inflammatory (LOX inhibition) and antimicrobial activities. Compounds 6 and 8 showed the highest antioxidant activity in all tests, where luteolin (8) showed the relatively best anti-inflammatory activity compared to other samples with 54.1 ± 5.0% inhibition at 1 µg/mL. All the tested compounds showed weak antimicrobial activity against tested microorganisms. This is the first phytochemical and bioactivity study on V. bugulifolium.[Figure: see text].

Anti-inflammatory, analgesic and in vivo-in vitro wound healing potential of the Phlomis rigida Labill. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The preparations of Phlomis aerial parts are used traditionally in Anatolia for wound healing and in inflammatory disorders. METHODS: For the identification of the active fraction, the air dried aerial parts of Phlomis rigida Labill. were extracted by methanol and fractionated successively by n-hexane, dichloromethane and ethyl acetate, respectively. The phenolic constituents were characterized by the Folin-Ciocaltheu method; the antioxidant activity was performed by ABTS and DPPH radical scavenging assays. In vitro anti-inflammatory activity was evaluated by LOX enzyme inhibition, spectrophotometrically as well as cell cultures. The wound healing properties of P. rigida extract gels were studied via in vitro cell culture methods and in vivo by excisional wound model using Balb-c mice. The P. rigida extract was analyzed and characterized by GC-FID, GC-MS, and LC-MS. RESULTS: The P. rigida methanol extract showed moderate LOX inhibitory at IC50 = 19.5 ± 2.8 µg/mL whereas the antioxidant activity was by DPPH• IC50 = 0.89 mg/mL, and by ABTS• IC50 = 0.99 mg/mL, respectively. In addition, a remarkable P. rigida extracts anti-inflammatory activity was observed in the cell culture assay, which was then confirmed by the in vitro wound healing activity applied at 0.125-0.5 mg/mL concentrations, resulting in a dose-dependent increase in wound closure at the final stage. The P. rigida gel formulation was prepared to evaluate the extract in vivo, whereas the experimental results of the new gel formulation supported the findings of the in vitro wound healing activity. CONCLUSION: The findings of this in vitro and in vivo study suggest that the wound healing and anti-inflammatory properties provide a scientific evidence of the ethnopharmacological application of Phlomis species.

Synergistic antibacterial combination of Lavandula latifolia Medik. essential oil with camphor.

Combination of various compounds and essential oils for pharmaceutical formulations withdraw attention. In this present study, it was aimed to evaluate the in vitro potential synergistic antibacterial effect of Lavandula latifolia (spike lavender) essential oil with camphor by using the checkerboard method against the human pathogens; Staphylococcus aureus and Listeria monocytogenes. Pharmacopoeia quality L. latifolia essential oil and racemic camphor were analyzed and verified by GC-FID and GC/MS, simultaneously. In vitro antibacterial activity of essential oil and camphor (MIC range: 0.16-20 mg/mL) and standard antimicrobial clarithromycin (MIC range: 0.125-16 µg/mL) were carried out by broth microdilution against S. aureus and L. monocytogenes standard strains, respectively. Resulting antibacterial effects were evaluated for their fractional inhibitory concentrations (FICs) as antagonistic, additive and synergistic effects. The analytical results showed that the major component of essential oil was linalool (45.2%) and 1,8-cineole (25.6%). Antibacterial effects of essential oil were determined as MIC 1.25-5 mg/mL. As a result of the experiments, L. latifolia essential oil-camphor combinations were identified as "synergistic (FIC ≤ 0.5), and additive (0.5 < FIC ≤ 1)" in the respective combinations, suggesting further evaluation for formulations for potential antimicrobial applications in food and pharmaceuticals.

In Vivo Wound Healing and In Vitro Anti-Inflammatory Activity Evaluation of Phlomis russeliana Extract Gel Formulations.

The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH• assay showed IC50 = 0.89 mg/mL, and the ABTS• assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC-FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.

Chemical Characterization and Biological Activity of the Mastic Gum Essential Oils of Pistacia lentiscus Var. Chia from Turkey.

The essential oils (EOs) were isolated by hydrodistillation from wild and cultivated Pistacia lentiscus L. var. chia-mastic gum tree (Anacardiaceae) from two natural habitats, namely from Cesme-Uzunkoy (1) and Mordogan (2), and one cultivated source, Cesme-Germiyan (3), in Izmir, Turkey. This comparative study evaluated the chemical composition and biological activity of mastic gum essential oils (MGEOs). For this purpose, MGEOs 1-3 were analyzed by gas chromatography-flame ionization detection (GC-FID), gas chromatography-mass spectrometry (GC-MS), and chiral GC for α-pinene. Laboratory assays were conducted to assess for potential in vitro cytotoxicity (multiple in vitro cancer cell lines), antimicrobial properties (five bacterial species and yeast), anti-inflammatory activity (inhibition of inducible nitric oxide synthase, iNOS), and the attraction of Ceratitis capitata (Mediterranean fruit fly, medfly), respectively. Chemical analysis indicated that MGEOs 1 and 2 were rich in α-pinene (56.2% and 51.9%), myrcene (20.1% and 18.6%), and ß-pinene (2.7% and 3.1%), respectively; whereas MGEO-3 was characterized by a high level of α-pinene (70.8%), followed by ß-pinene (5.7%) and myrcene (2.5%). Chiral GC analyses showed that concentration ratios between (-)/(+)-α-pinene and (-)-α-pinene/myrcene allowed for differentiation between wild and cultivated MGEO sources. In biological assays, MGEOs 1-3 did not exhibit significant antimicrobial effects against the pathogens evaluated and were not strong attractants of male medflies; however, all three MGEOs displayed a dose-dependent inhibition of iNOS, and MGEOs 1 and 2 exhibited selective in vitro cytotoxicity against human cancer cells. These results suggest that wild-type mastic gum oils from Cesme and Mordogan (MGEOs 1 and 2) are potential sources of beneficial products and warrant further investigation.

Antiprotozoal Activity of Turkish Origanum onites Essential Oil and Its Components.

Essential oil of Origanum species is well known for antimicrobial activity, but only a few have been evaluated in narrow spectrum antiprotozoal assays. Herein, we assessed the antiprotozoal potential of Turkish Origanum onites L. oil and its major constituents against a panel of parasitic protozoa. The essential oil was obtained by hydrodistillation from the dried herbal parts of O. onites and analyzed by Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). The in vitro activity of the oil and its major components were evaluated against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. The main component of the oil was identified as carvacrol (70.6%), followed by linalool (9.7%), p-cymene (7%), γ-terpinene (2.1%), and thymol (1.8%). The oil showed significant in vitro activity against T. b. rhodesiense (IC50 180 ng/mL), and moderate antileishmanial and antiplasmodial effects, without toxicity to mammalian cells. Carvacrol, thymol, and 10 additional abundant oil constituents were tested against the same panel; carvacrol and thymol retained the oil's in vitro antiparasitic potency. In the T. b. brucei mouse model, thymol, but not carvacrol, extended the mean survival of animals. This study indicates the potential of the essential oil of O. onites and its constituents in the treatment of protozoal infections.

Anti-inflammatory and antibacterial evaluation of Thymus sipyleus Boiss. subsp. sipyleus var. sipyleus essential oil against rhinosinusitis pathogens.

Thymus sipyleus Boiss. subsp. sipyleus var. sipyleus of the Lamiaceae, locally known as thyme scented lemon, which is an endemic taxon collected from Sivas in Anatolia, was investigated in this study due to its folk medicine use against rhinosinusitis. The aromatic characteristics of the plant material gave the idea for the detailed evaluation of the volatiles and essential oil thereof. Consequently, the oil was obtained by Clevenger type hydrodistillation followed by gas chromatography-flame ionization detector (GC-FID) and gas chromatography/mass spectrometry (GC/MS) analyses for phytochemical characterization. To confirm the folk medicinal use against sinusitis, in vitro antimicrobial activities of the essential oil was evaluated by agar diffusion, microdilution and vapour diffusion methods against selected rhinosinusitis associated strains such as Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, Streptococcus pyogenes, S. pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae and Moraxella catarrhalis. Additionally, the in vitro anti-inflammatory activity was evaluated by 5-lipoxygenase (5-LOX) inhibitory effect of the essential oil spectrophotometrically. Furthermore, the composition of the volatiles of the vapour phase of the oil was determined by headspace-solid phase microextraction (HS-SPME-GC/MS) after 15 min and 24 h in accordance with antimicrobial vapour diffusion method conditions, respectively. According to the analytical results, the main component was determined as thymol (66.2%). Whereas in the HS-SPME method p-cymene (26.1%) and γ-terpinene (26%) were identified as the main volatile components within the 15. min., and thymol (75.3%) after 24 h, respectively. The antibacterial activity against rhinosinusitis pathogens varied between 160 and 1250 µg/mL minimum inhibitory concentrations, with the best inhibitory effects observed against the S. aureus, S. pyogenes and M. catarrhalis. The anti-inflammatory activity of the oil was determined as 12.1 ±â€¯1.8% in 100 µg/mL. The results showed the in vitro antimicrobial and anti-inflammatory potential of the oil also in vapour phase against sinusitis supporting the traditional use.

Rhanterium epapposum Oliv. essential oil: Chemical composition and antimicrobial, insect-repellent and anticholinesterase activities.

The essential oil (EO) of the aerial parts of Rhanterium epapposum Oliv. (Asteraceae), was obtained by hydrodistillation. The oil was subsequently analyzed by both GC-FID and GC-MS, simultaneously. Forty-five components representing 99.2% of the oil composition were identified. The most abundant compounds were camphene (38.5%), myrcene (17.5%), limonene (10.1%) and α-pinene (8.7%). Referring to the ethnobotanical utilization, an insecticidal assay was performed, where the oil repelled the yellow fever mosquito Aedes aegypti L. at a minimum effective dose (MED of 0.035 ± 0.010 mg/cm2) compared to the positive control DEET (MED of 0.015 ± 0.004 mg/cm2). Additionally, the in vitro antimicrobial activity against a panel of pathogens was determined using a microdilution method. The acetyl- and butyrylcholine esterase inhibitory activities were measured using the colorimetric Ellman method. The bioassay results showed that the oil was rather moderate in antimicrobial and cholinesterase inhibitions when compared to the standard compounds.

Secondary Metabolites from the Leaves of Digitalis viridiflora.

A new phenylethanoid glycoside, named digiviridifloroside (1), was isolated from the leaves of Digitalis viridiflora Lindley along with a known phenylethanoid glycoside, calceolarioside A (2), two flavonoid glycosides, scutellarein 7-Ο-ß-D-glucopyranoside (3) and hispidulin 7-0-ß-D-glucopyranoside (4), two cleroindicins, cleroindicins B (5) and F (6), a nucleoside, adenosine (7), as well as a mixture of ß-glucopyranosyl-(1-6)-4-O-caffeoyl-α/ß glucopyranose and 3,4-dihydroxyphenylethanol. The structure of the new compound was established as 3,4-dihydroxy-ß-phenylethoxy-6-O-(E)-feruloyl-ß- glucopyranosyl-(l->6)-4-0-(E)-caffeoyl-ß-glucopyranoside (1) based on extensive ID- and 2D-NMR spectroscopy, as well. as HR-ESI-MS. Digiviridifloroside represents a rare type of phenylethanoid glycoside which bears two aromatic acyl units in its structure. In addition to phytochemical studies, the isolates were evaluated for their in vitro antimicrobial activities against three pathogenic bacteria and three yeast strains using a microdilution method. Among the tested compounds, 5 exhibited moderate antibacterial activity against Bacillus cereus NRRLB 3711 with a MIC value of 25 µg/mL, whereas compounds 5 and 6 showed relatively high anticandidal activity against Candida strains with MIC values down to 12.5 µg/mL, in comparison to the standard antimicrobial compounds.

Anticandidal Effects of Thymoquinone: Mode of Action Determined by Transmission Electron Microscopy (TEM).

Thymoquin6ne (TQ) is one of the bioactive constituents of black cumin seed (Nigella sativa L.) oil. It is well known that this natural volatile quinone has remarkable antimicrobial effects, especially against Candida species. Consequently, in this present study TQ was evaluated for its anticandidal effects against. 14 differet.pathogenic Candida strains by using the in vitro, partly modified, microdilution CLSI M27-A2 method. After TQ treatment at the minimum inhibitory concentration (MIC), ultra-thin sections of C. albicans cells were thoroughly evaluated by transmission electron microscopy (TEM). The mode of action of TQ on different Candida cells was elaborated, where their disintegration and disorganization with amorphous nucleus were observed microscopically.

Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities.

A new prenylated isoflavan, iconisoflavan (1), and a new prenylated isoflav-3-ene, iconisoflaven (2) were isolated from the roots of Glycyrrhiza iconica together with four known ones namely (3S)-licoricidin (3), licorisoflavan A (4), topazolin (5) and glycycoumarin (6). The structures were elucidated on the basis of extensive spectroscopic analysis including 1D and 2D NMR as well as HR-MS. Furthermore, the absolute configurations of compounds 1, 3 and 4 were established by electronic circular dichroism (ECD). All the isolated compounds (1-6) were evaluated for their in vitro antimicrobial activities against five pathogenic bacteria and one yeast (Candida albicans) using an in vitro microdilution method. Compounds 1 and 3-5 displayed significant activity against Salmonella typhimurium ATCC 13311 with MIC values ranging from 2 to 8 µg/mL. Additionally, all compounds were screened for their in vitro free radical scavenging activities using an in vitro microdilution DPPH assay spectrofotometrically. The tested compounds exhibited IC50 values in the range of 0.18-0.56 mg/mL, suggesting an activity comparable with that of ascorbic acid (IC50: 0.07 mg/mL). To the best of our knowledge, the present study constitutes the first phytochemical and bioactivity investigation on G. iconica.

Efficacy of capecitabine monotherapy as the first-line treatment of metastatic HER2-negative breast cancer.

AIMS AND BACKGROUND: Capecitabine is a potent and safe agent that can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of capecitabine monotherapy as a first-line treatment in human epidermal receptor 2 (HER2)-negative patients with MBC. METHODS AND STUDY DESIGN: In this single-center trial, a total of 109 HER2-negative patients with MBC who received capecitabine monotherapy as first-line treatment between 2003 and 2014 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression-free survival (PFS) and for overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. RESULTS: Median PFS was 7.0 ± 0.67 (confidence interval (CI) 5.6-8.3) months and median OS was 30 ± 4.1 (CI 21.8- 38.1) months. First-line capecitabine treatment for HER2-negative MBC was more effective in the estrogen receptor (ER)-positive patient population compared to the ER-negative group (median PFS 9 vs 4 months (p = 0.002), median OS 33 vs 21 months (p = 0.01)). Indeed, the overall response rate in the ER-negative group was 16%, while this was calculated as 38% for ER-positive cases. While most of our patient population was treated with a higher dose (1250 mg/m2), the observed grade 3-4 toxicities were lower compared to some previously reported phase II and phase III capecitabine studies. CONCLUSIONS: Capecitabine monotherapy is an effective and safe regimen for ER-positive, HER2-negative patients with MBC. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease of its oral administration make this agent a preferable option for both physicians and patients.

Supplemental carvacrol can reduce the severity of inflammation by influencing the production of mediators of inflammation.

Carvacrol (CVC) is a monoterpenic phenol, which is present in the essential oil of various plants. It has been widely used both as antibacterial feed additive and food preservative. Therefore, our objective was to evaluate the prophylactic effects of carvacrol on inflammatory mediators of sepsis. Serum tumor necrosis factor alpha and interleukin 6 levels as proinflammatory markers were evaluated using an enzyme-linked immunosorbent assay technique. Malondialdehyde (MDA) was determined in the sample by using thiobarbituric acid test. Nitric oxide (NO) levels and arginase activity and also all measurements were evaluated after 24 h from lipopolysaccharide (LPS) injections done (1 mg/kg i.p.). All carvacrol doses (20, 40, and 80 mg/kg) were given by intra gastric gavage during six days before LPS injection (7th day). Proinflammatory cytokines, MDA, NO levels, and arginase activity were decreased by carvacrol according to the carvacrol doses. These results indicate that carvacrol may have a potent anti-inflammatory and antioxidant effects in a dose-dependent manner. Subchronic use of CVC can be assisted to pre-treat of sepsis as a prophylactic.

The in vivo evaluation of anti-angiogenic effects of Hypericum essential oils using the chorioallantoic membrane assay.

CONTEXT: Hypericum species including Hypericum confertum Choisy, H. hircinum L., H. hyssopifolium Chaix. subsp. elongatum (Ledeb.) Woron var. microcalycinum (Boiss. & Heldr.) Boiss. and H. perforatum L. (Clusiaceae) are used as medicinal plants in Turkey. OBJECTIVE: The anti-angiogenic evaluation of Hypericum essential oils using the chick embryo chorioallantoic membrane (CAM) assay are performed with this study for the first time. MATERIALS AND METHODS: The anti-angiogenic activity of Hypericum essential oils (0.5-5.0 mg/ml) was evaluated in vivo using the CAM assay, compared to standard anti-angiogenic substances at the same concentrations, in trice replicated independent assays. GC and GC-MS analyses were carried out simultaneously to identify the chemical compositions of the Hypericum essential oils. RESULTS: The CAM treated with H. perforatum essential oil showed anti-angiogenic effect (score 0.6 ± 0.3) at 50 µg/pellet concentration, whereas other tested Hypericum essential oils showed no effect compared to the standards (e.g. suramin score 0.5 ± 0.2). Furthermore, the tested oils showed neither membrane toxicity nor irritation at the tested concentrations. The major compound of the essential oil of H. confertum was identified as germacrene D (30.2%). The major compound of the essential oils of the H. hircinum. H. hyssopifolium subsp. elongatum var. microcalycinum and H. perforatum was identified as α-pinene (88.3, 57.8, 33.3%), respectively. DISCUSSION AND CONCLUSION: Hypericum species and in particular H. perforatum essential oil may have important effect toward wound healing and various inflammations. The data obtained in this experiment suggest further investigations on various cancers due to its anti-angiogenic effects observed.