The essential oils chemical compositions and antimicrobial,antioxidant activities and toxicity of three Hyptis species

Abstract

Context: Hyptis suaveolens (Linn.) Poit., Hyptis rhomboidea Mart. et Gal., and Hyptis brevipes Poit., are three species of Hyptis Jacq. (Lamiaceae). Hyptis suaveolens is used for the treatment of fever, headache, gastrointestinal bloating and rheumatism in the traditional folk medicine; Hyptis rhomboidea for hepatitis, ulcer and swollen poison; and Hyptis brevipes for asthma and malaria.

Objective: To characterize chemical compositions of the oils from three Hyptis species and evaluate their potential antimicrobial, radical scavenging activities and toxicities against brine shrimp.

Materials and methods: The oils were obtained by hydrodistillation, and their chemical compositions were investigated by gas chromatography-mass spectrometry (GC-MS). Minimum inhibitory concentrations (MICs) were determined using the tube double-dilution technique. The antioxidant activities were investigated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and toxicities by the brine shrimp bioassay.

Results: Forty-seven, 33 and 28 constituents of oils isolated, respectively, from H. suaveolens, H. rhomboidea and H. brevipes were identified. Among the essential oils, the strongest antioxidant activity was exhibited by H. brevipes with an SC₅₀ value of 2.019?±?0.25?μg?mL^?1. The H. brevipes oil exhibited the strongest antimicrobial activity (3.125–6.25?μg?mL^?1) on pathogens employed in the assay. They all showed significant toxicities with median lethal concentration (LC₅₀) values of 62.2?±?3.07?μg?mL^?1, 65.9?±?6.55?μg?mL^?1 and 60.8?±?9.04?μg?mL^?1, respectively.

Discussion and conclusions: The three Hyptis species oils possess strong antimicrobial activities and toxicities. Hyptis rhomboidea and H. brevipes showed considerable antioxidant activity compared to the positive control.     

Biological activities of ethyl acetate extract of different parts of Hyssopus angustifolius

Context: Hyssopus angustifolius M. Bieb. (Lamiaceae) is one of the most important medicinal plants in Iranian traditional medicine for the treatment of lung inflammation, laryngitis and cough relief. Much attention has been paid to this medicinal plant because of its traditional uses.

Objective: The present study examined the antioxidant and antihemolytic activities of ethyl acetate extract of stems, leaf and flowers of Hyssopus angustifolius.

Materials and methods: Antioxidant activity of extracts was evaluated by employing six different models, i.e., DPPH, nitric oxide and hydrogen peroxide scavenging, metal chelating and reducing power activities and hemoglobin-induced linoleic acid system. Also, antihemolytic activity was evaluated against hydrogen peroxide-induced hemolysis.

Results: Flowers extract showed the better activity than leaf and stems extracts in DPPH radical scavenging activity (IC₅₀ was 275.4?±?7.6 μg mL^?1). Leaf, stems and flowers extracts showed good nitric oxide scavenging activity (IC₅₀ were 376.6?±?11.4 µg mL^?1 for flowers, 297.6?±?9.6 μg mL^?1 µg mL^?1 for leaves and 837.8?±?19.2 µg mL^?1 for stems). The leaf extract exhibited better hydrogen peroxide scavenging and Fe²⁺ chelating activity than stems and flowers extracts. In hemoglobin-induced linoleic acid system, all of the extracts exhibited very good activity. Also, extracts show weak reducing power activity. The ethyl acetate extract of leaf showed better antihemolytic activity than the flower and stems (IC₅₀ was 94.0?±?2.4 μg mL^?1).

Discussion and conclusion: These findings give a scientific basis to the traditional usage of Hyssopus angustifolius, also showing its potential as rich sources of natural antioxidant compounds.     

Nanosizing of valsartan by high pressure homogenization to produce dissolution enhanced nanosuspension: pharmacokinetics and pharmacodyanamic study

Purpose: The purpose of the present study was to formulate and evaluate nanosuspension of Valsartan (VAL), a poorly water soluble and low bioavailable drug (solubility of 0.18?mg?mL^?1; 23% of oral bioavailability) with the aim of improving the aqueous solubility thus the bioavailability and consequently better anti-hypertensive activity.

Methods: Valsartan nanosuspension (VAL-NS) was prepared using high-pressure homogenization followed by lyophilisation. The screening of homogenization factors influencing nanosuspension was done by 3-factorial, 3-level Box-Behnken statistical design. Model suggested the influential role of homogenization pressure and cycles on drug nanosizing. The optimized formulation containing Poloxamer^?188 (PXM 188) was homogenized for 2 cycles at 500 and 1000?bar, followed by 5 cycles at 1500 bars.

Results: The size analysis and transmission electron microscopy showed nanometric size range and uniform shape of the nanosuspension. The in vitro dissolution showed an enhanced release of VAL from nanosuspension (VAL-NS) compared to physical mixture with PXM 188. Pharmacodynamic results showed that, oral administration of VAL-NS significantly lowered (p?≤?0.001) blood pressure in comparison to non-homogenized VAL (VAL-Susp) in Wistar rat. The level of VAL in rat plasma treated with VAL-NS showed significant difference (p?≤?0.005) in C_max (1627.47?±?112.05?ng?mL^?1), T_max (2.00?h) and AUC_0→24 (13279.2?±?589.426?ng?h?mL^?1) compared to VAL-Susp that was found to be 1384.73?±?98.76?ng?mL^?1, 3.00?h and 9416.24?±?218.48?ng?h?mL^?1 respectively. The lower T_max value, proved the enhanced dissolution rate of VAL.

Conclusion: The overall results proved that newly developed VAL-NS increased the plasma bioavailability and pharmacodyanamic potential over the reference formulation containing crude VAL.     

Essential oil composition and antinociceptive activity of Thymus capitatus

Context: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties.

Objective: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures.

Materials and methods: Gas chromatography–mass spectrometry was used to identify and quantify the constituents of the T. capitatus EO. The antinociceptive activity was evaluated in vivo by the glutamate-induced nociception model in male Swiss mice (25?g), at doses of 3, 6 and 12?mg/kg, 1?h before evaluation of the licking time response (0–15?min). The mechanism of T. capitatus EO (1–500?μg/mL) on the isolated nerve excitability of Wistar rat (300?g) was assessed by the single sucrose technique.

Results and discussion: The EO of T. capitatus presented 33 components, mainly monoterpenes and sesquiterpenes, carvacrol (ca. 80%) was its major constituent. T. capitatus EO induced antinociception in orally treated mice (3, 6, and 12?mg/kg) reducing the licking time from control (100.3?±?11.9?s) to 84.8?±?12.2, 62.7.6?±?9.9, and 41.5?±?12.7?s, respectively (n?=?8; p?T. capitatus EO (500?μg/mL) decreased the compound action potential amplitude (V_CAP) of about 80.0?±?4.3% from control recordings (n?=?4; p?+?channels.

Conclusions: The present study demonstrated the antinociceptive activity of Thymus capitatus essential oil, which acts via peripheral nervous excitability blockade.     

Mosquito and tick repellency of two Anthemis essential oils from Saudi Arabia

The essential oils (EOs) of Anthemis melampodina (Am) and Anthemis scrobicularis (As) (Asteraceae) were extracted from the aerial parts of the plants by hydrodistillation, and their chemical compositions were analyzed using GC-FID and GC-MS. Fifty-six components representing 85.5% of the oil composition of Anthemis melampdina were identified, and the major components were α-pinene (17.1%) and β-eudesmol (13.8%). Forty-one components representing 86% of the oil composition of Anthemis scrobicularis were identified, and the major component was β-eudesmol (12.8%). Laboratory bioassays were conducted to determine repellency of Am and As EOs against the yellow fever mosquito Aedes aegypti L. and the lone star tick Amblyomma americanum L. The minimum effective doses (MEDs) of the Am and As EOs against mosquitoes were 0.187?±?0.000 and 0.312?±?0.063?mg/cm² respectively, which were significantly higher than that of DEET (0.023?±?0.000?mg/cm²) in human-based repellent bioassays. The As EO was more repellent than Am EO against nymphal ticks but was less effective than DEET in vertical paper bioassays.     

Differential effects of the essential oils of Lavandula luisieri and Eryngium duriaei subsp. juresianum in cell models of two chronic inflammatory diseases

Abstract

Context: Effective drugs to treat osteoarthritis (OA) and inflammatory bowel disease (IBD) are needed.

Objective: To identify essential oils (EOs) with anti-inflammatory activity in cell models of OA and IBD.

Materials and methods: EOs from Eryngium duriaei subsp. juresianum (M. Laínz) M. Laínz (Apiaceae), Laserpitium eliasii subsp. thalictrifolium Sennen & Pau (Apiaceae), Lavandula luisieri (Rozeira) Rivas-Martínez (Lamiaceae), Othantus maritimus (L.) Hoff. & Link (Asteraceae), and Thapsia villosa L. (Apiaceae) were analyzed by GC and GC/MS. The anti-inflammatory activity of EOs (5–200?μg/mL) was evaluated by measuring inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) activation (total and phosphorylated IκB-α), in primary human chondrocytes and the intestinal cell line, C2BBe1, stimulated with interleukin-1β (IL-1β) or interferon-γ (IFN-γ), IL-1β and tumor necrosis factor-α (TNF-α), respectively.

Results: The EO of L. luisieri significantly reduced iNOS (by 54.9 and 81.0%, respectively) and phosphorylated IκB-α (by 87.4% and 62.3%, respectively) in both cell models. The EO of E. duriaei subsp. juresianum caused similar effects in human chondrocytes, but was inactive in intestinal cells, even at higher concentrations. The EOs of L. eliasii subsp. thalictrifolium and O. maritimus decreased iNOS expression by 45.2?±?8.7% and 45.2?±?6.2%, respectively, in C2BBe1 cells and were inactive in chondrocytes. The EO of T. villosa was inactive in both cell types.

Discussion and conclusion: This is the first study showing anti-inflammatory effects of the EOs of L. luisieri and E. duriaei subsp. juresianum. These effects are specific of the cell type and may be valuable to develop new therapies or as sources of active compounds with improved efficacy and selectivity towards OA and IBD.     

Chemical composition of essential oil and oleoresins of Zingiber officinale and toxicity of extracts/essential oil against diamondback moth (Plutella xylostella)

Abstract

Essential oil (EO) of ginger and oleoresins isolated from extraction solvents by GC–MS. Zingiberene was the major constituent in all the samples, and ethanol could extract the maximum quantity (21.2%) from the dried de-oiled cake (EDD) followed by EO (20.3%) as compared to oleoresins. Hydro-distilled EO contains higher oxygenated monoterpenes (22.4%) than oleoresins. EDD showed more toxicity to larvae of Plutella xylostella (LC₅₀?=?4957.9?mg L^?1) after 96?h and was followed by EDW (LC₅₀?=?5067.6?mg L^?1) and EF (LC₅₀?=?6631.2?mg L^?1). EO also showed promising efficacy (LC₅₀?=?5875.9?mg L^?1) and repellency (97.1%) against P. xylostella.     

Antioxidant,anticholinesterase and antibacterial activities of Stachys guyoniana and Mentha aquatica

Context: Stachys guyoniana Noë ex. Batt. and Mentha aquatica L. are two Algerian Lamiaceae used in folk medicine.

Objective: To investigate their antioxidant, anticholinesterase and antibacterial activities.

Material and methods: n-Butanol (BESG), ethyl acetate (EESG) and chloroform (CESG) extracts of S. guyoniana and methanol (MEMA) and chloroform (CEMA) aerial part extracts of M. aquatica and methanol (MERMA) and acetone (AERMA) roots extracts of M. aquatica were evaluated for their antioxidant activity by the β-carotene-linoleic acid, DPPH^? and ABTS^?+?scavenging, CUPRAC and metal chelating assays. The anticholinesterase activity was tested against AChE and BChE. The antibacterial activity was assessed by MICs determination against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella heidelberg, Klebsiella pneumoniae, Enterobacter aerogenes and Morganella morganii strains.

Results: In the β-carotene test, the CESG (IC₅₀: 2.3?±?1.27?μg/mL) exhibited the highest activity. The BESG was the best scavenger of DPPH^? (IC₅₀: 2.91?±?0.14?μg/mL). In the ABTS test, AERMA was the most active (IC₅₀: 4.21?±?0.28?μg/mL). However, with the CUPRAC, the BESG exhibited the best activity (A_0.50: 0.15?±?0.05?μg/mL) and was active in metal chelating assay with 48% inhibition at 100?μg/mL. The BESG was the best AChE inhibitor (IC₅₀: 5.78?±?0.01?μg/mL) however, the AERMA showed the highest BChE inhibitory activity (IC₅₀: 19.23?±?1.42?μg/mL). The tested extracts exhibited a good antibacterial activity.

Conclusion: This study demonstrated good antioxidant, anticholinesterase and antibacterial potential of S. guyoniana and M. aquatica, which fits in well with their use in folk medicine.     

Evaluation of antioxidant and hepatoprotective effects of white cabbage essential oil

Context: There have been no reports of the extraction of essential oil (EO) from white cabbage [Brassica oleracea L. var. capitata (L.) Alef. f. alba DC. (Brassicaceae)] (Bocfal) or its chemical composition, antioxidant activity, or hepatoprotective effects.

Objective: To extract Bocfal EO, to identify and quantify its chemical components, to assess their antioxidant capacity, and to evaluate the hepatoprotective properties of Bocfal EO.

Materials and methods: Bocfal EO was obtained using hydrodistillation (200?mm Hg/58?°C). The chemical composition was analyzed using GC-MS and was quantified using GC-FID. The antioxidant activity of Bocfal EO and its main constituents was evaluated using TBARS in rat brain homogenates. A Bocfal EO hepatoprotective effect (192?mg/kg) on acute carbon tetrachloride (CT)-induced liver damage was determined in rats using biochemical markers and histological analysis. Diallyl disulphide (DADS) (1?mmol/kg) was used as a control for comparison.

Results: Bocfal EO contained organic polysulphides (OPSs), such as dimethyl trisulphide (DMTS) 65.43?±?4.92% and dimethyl disulphide (DMDS) 19.29?±?2.16% as major constituents. Bocfal EO and DMTS were found to be potent TBARS inhibitors with IC₅₀ values of 0.51 and 3?mg/L, respectively. Bocfal EO demonstrated better hepatoprotective properties than did DADS (p?per se, as observed using histopathology.

Discussion and conclusion: The antioxidant properties of Bocfal EO and DMTS may be the mechanism of hepatoprotective action; the parenchymal disturbances by Bocfal EO or DADS alone may be related to the high doses used.     

Phytochemical composition,anti-inflammatory activity and cytotoxic effects of essential oils from three Pinus spp.

Context: Inflammation and cell differentiation lead to a number of severe diseases. In the recent years, various studies focused on the anti-inflammatory and anticancer activity of essential oils (EOs) of numerous plants, including different Pinus species.

Objective: The phytochemical composition, anti-inflammatory and cytotoxic activity of EOs from needles and twigs of Pinus heldreichii Christ (Pinaceae) and P. peuce Griseb., and from needles, twigs and cones of P. mugo Turra were determined.

Materials and methods: For separation and identification of the EOs, gas chromatography/flame ion detector (GC/FID) and GC/mass spectrometry were performed. The amount of secreted IL-6 in a lipopolysaccharide (LPS)-stimulated macrophage model was quantified (concentration of oils: 0.0001–0.2%, 3?h incubation). Cytotoxicity on the cancer cell lines HeLa, CaCo-2 and MCF-7 were determined using a MTT (Thiazolyl Blue Tetrazolium Bromide) assay (concentration of oils: 0.001–0.1%, 24?h incubation).

Results: The most prominent members in the oils include: δ-3-carene, α-pinene and linalool-acetate (P. mugo); α-pinene, β-phellandrene and β-pinene (P. peuce); limonene, α-pinene and (E)-caryophyllene (P. heldreichii). EOs showed significant cytotoxic effects on cancer cell lines (IC₅₀ 0.007 to >0.1%), with a reduction in cell viability with up to 90% at a concentration of 0.1%, and anti-inflammatory activity (IC₅₀ 0.0008–0.02%) with a reduction of IL-6 secretion with up to 60% at a concentration of 0.01%.

Discussion and conclusion: The EOs of needles and twigs from P. peuce and P. heldreichii as well as of needles, twigs and cones of P. mugo can be considered as promising agents for anticancer and anti-inflammatory drugs.     

The role of human cytochrome P450 enzymes in metabolism of acrylamide in vitro

Abstract

Objective: Acrylamide (AA), a probable human carcinogen, is present in fried and baked starch-rich food. In vivo, the substance is partly biotransformed to glycidamide (GA), which may account for carcinogenic effects. Existing data suggest an important but not exclusive contribution of CYP2E1 to GA formation. The aim of this project was to derive respective enzyme kinetic parameters for CYP2E1 and to assess a possible role of other important human CYPs for this reaction in vitro.

Methods: AA (0.2–20?mM) was incubated with human liver microsomes (HLM) and human cytochrome P450 enzymes (supersomes?). GA was quantified by a specific LC-MS/MS method. Enzyme kinetic parameters were estimated assuming a single binding site. Furthermore, inhibition experiments were performed with diethyldithiocarbamate (DDC), a potent inhibitor of CYP2E1.

Results: The mean?±?SD maximum formation rate (V_max) and Michaelis–Menten constant (K_m) for GA formation in HLM were 199?±?36?pmol GA/mg protein/min and 3.3?±?0.5?mM, respectively. In AA incubations with supersomes?, only for CYP2E1 measurable GA formation was detected in all tested AA concentrations (V_max and K_m were 5.4?nmol GA/nmol CYP2E1/min and 1.3?mM, respectively). Inhibition constant (IC₅₀) of DDC was 3.1?±?0.5?µM for HLM and 1.2?±?0.2?µM for CYP2E1 supersomes?. Therefore, relevant participation of CYPs other than CYP2E1 in the metabolism of AA to GA in humans does not seem likely.

Conclusion: Our results confirm the major role of CYP2E1 in GA formation from AA, albeit with low affinity and low capacity. Further studies are needed to identify other pathways of GA formation.     

Antioxidant and anticholinesterase activities of five wild mushroom species with total bioactive contents

Abstract

Context: Recently, mushrooms are interesting natural products to be investigated due to exhibiting various bioactivities.

Objective: This study determines the antioxidant and anticholinesterase activities of various extracts of five wild mushroom species. In addition, the total bioactive contents, namely, ascorbic acid, β-carotene, and lycopene along with phenolic and flavonoid contents were also determined spectrophotometrically.

Materials and methods: Antioxidant activity was tested by using five complementary tests; namely, β-carotene-linoleic acid, DPPH^? scavenging, ABTS^?+ scavenging, cupric-reducing antioxidant capacity (CUPRAC), and metal chelating assays. The in vitro anticholinesterase activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the Ellman method. The spectrophotometric methods were used to determine the total phenolic, flavonoid, ascorbic acid, β-carotene, and lycopene contents.

Results: The current study has shown that ethyl acetate extracts of Ganoderma lucidum (Curtis) P. Karst (IC₅₀: 1.55?±?0.05?µg/mL) and Funalia trogii (Berk.) Bondartsev & Singer (IC₅₀: 4.31?±?0.18?µg/mL) exhibited good lipid peroxidation inhibitory activity. The DPPH, ABTS, and CUPRAC assays supported this activity. The ethyl acetate and methanol extracts of Funalia trogii and Ganoderma lucidum indicated good anticholinesterase activity. Ganoderma lucidum had rich phenolic and flavonoid contents, indicating 98.67?±?0.32?mg PEs/g extract and 160.38?±?1.25?mg QEs/g extract, respectively.

Discussion and conclusion: The results demonstrate that some of the mushroom species tested herein could be used in food and pharmaceutical industries as natural antioxidants.     

Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact

Context: Mefenamic acid (MEF) and the dried root of Scutellaria baicalensis Georgi (Radix Scutellariae, RS) share a high possibility of combined medication to treat inflammation.

Objective: The present study investigates the impact of MEF on absorption/disposition of three major components in RS (baicalein, B; wogonin, W; oroxylin A, OA) and further pharmacological changes.

Materials and methods: The apparent permeability (P_app) and percentage of metabolism of B, W and OA at 10?μΜ were measured at the absence/presence of MEF (100?μΜ) in the Caco-2 cell monolayer model. A modified whole blood assay was employed to quantify prostaglandin E₂ (PGE₂) 4, 6 and 8?h post-oral administration with water suspension of MEF at 40?mg/kg and RS at 200?mg/kg.

Results: In the presence of MEF, P_app of B, W and OA were increased from 1.69?±?0.89?×?10^?6, 1.57?±?0.10?×?10^?6 and 3.09?±?0.70?×?10^?6?cm/sec to 5.24?±?0.27?×?10^?6, 6.08?±?0.19?×?10^?6 and 4.13?±?0.38?×?10^?6, whereas their percentage of metabolism was decreased from 72.75?±?2.44%, 73.27?±?3.25% and 89.84?±?2.99% to 21.11?±?0.69%, 17.90?±?5.55% and 45.44?±?3.38%. PGE₂ level was much lower in the co-administration group (49.04?±?2.03?pg/ml) than in the MEF group (73.13?±?3.03?pg/ml) or RS group (494.37?±?11.75?pg/ml) 4?h post MEF dosing, suggesting a synergic effect.

Discussion and conclusion: Co-administration of MEF and RS could induce potential alterations in their pharmacokinetic profiles and anti-inflammatory effects.     

Analgesic activity of Eugenia jambolana leave constituent: A dikaempferol rhamnopyranoside from ethyl acetate soluble fraction

Context: Eugenia jambolana Lam. (Myrtaceae) is a medicinal plant used in folk medicine for the treatment of diabetes, inflammation, and pain.

Objective: We investigated the antinociceptive effect of kaempferol-7-O-α-l-rhamnopyranoside]- 4′-O-4′-[kaempferol-7-O-α-l-rhamnopyranoside (EJ-01), isolated from the E. jambolana leaves.

Materials and methods: EJ-01 (3, 10, and 30?mg?kg^?1, orally) was assessed for peripheral (formalin-nociception and acetic acid-writhing) and central (hot plate and tail flick test) analgesic activity in mice and the in vitro anti-inflammatory activity (25, 50, and 100?µg?mL^?1) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

Results and discussion: EJ-01 (10 and 30?mg?kg^?1) significantly inhibited mean writhing counts (37.74 and 36.83) in acetic acid writhing and paw licking time (55.16 and 45.66?s) in the late phase of the formalin test as compared with the respective control (60.66 and 104.33?s). EJ-01 did not show analgesic activity in central pain models. Significant reduction in the tumor necrosis factor (TNF)-α (295.48, 51.20, and 49.47?pg?mL^?1) and interleukin (IL)-1β (59.38, 20.08, and 15.46?pg?mL^?1) levels were observed in EJ-01-treated medium (25, 50, and 100?µg?mL^?1) as compared with vehicle-treated control values (788.67 and 161.77?pg?mL^?1), respectively. Significant reduction in total nitrite plus nitrate (NO_x) levels (70.80?nmol) was observed in the EJ-01-treated medium (100?µg?mL^?1) as compared with the vehicle-treated value (110.41?nmol).

Conclusion: EJ-01 is a valuable analgesic constituent of E. jambolana leaves and this study supports the pharmacological basis for the use of this plant in traditional medicine for curing inflammatory pain.     

Antioxidant,anticholinesterase and tyrosinase inhibition activities,and fatty acids of Crocus mathewii – A forgotten endemic angiosperm of Turkey

Context We report the first ever chemical/biochemical study on Crocus mathewii Kerndorff (Iridaceae) – a Turkish endemic angiosperm. This plant has never been explored for its phytochemistry and bioactivities.

Objective This study explores C. mathewii corm and aerial parts for the chemical and biological properties of hexane, ethyl acetate, methanol and water fractions of the extracts.

Material and methods Plant material (20 g) was extracted by methanol (250?mL?×?5, 3 days each) and fractioned into hexane, ethyl acetate, methanol and water. All fractions were subjected to β-carotene–linoleic acid, DPPH^·, ABTS^·+, CUPRAC, metal chelating and tyrosinase inhibition activities. Hexane fractions were submitted to GC–MS analysis.

Results Ethyl acetate fractions showed excellent IC₅₀ values in DPPH^· (aerial 36.21?±?0.76 and corm 33.87?±?0.02?mg/L) and ABTS^·+ (aerial 33.01?±?0.79 and bulb 27.87?±?0.33?mg/L); higher than the IC₅₀ of the standard α-tocopherol (DPPH 116.25?±?1.97; ABTS 52.64?±?0.37?mg/L), higher than BHA in DPPH (57.31?±?0.25?mg/L), but slightly lower in ABTS (19.86?±?2.73?mg/L). Methanol extract of aerial parts also showed higher activity than α-tocopherol in DPPH (85.56?±?11.51?mg/L) but slightly less (72.90?±?3.66?mg/L) than both the standards in ABTS. Linoleic (aerial 53.9%, corm 43.9%) and palmitic (aerial 22.2%, corm 18%) were found as the major fatty acids.

Discussion and conclusion Some fractions of C. mathewii showed higher antioxidant activities than the standards. There is a need to explore more about this plant.     

Anti-proliferative and matrix metalloproteinase-2 inhibition of Longkong (Lansium domesticum) extracts on human mouth epidermal carcinoma

Abstract

Context: Longkong [Lansium domesticum Corr. (Meliaceae)] is a popular tropical plant producing economic edible fruits found mainly in Southeast Asia. However, limited information is available concerning anticancer activity of Longkong.

Objective: To investigate anticancer activities in human mouth epidermal carcinoma (KB) of Longkong extracts.

Materials and methods: Various parts of Longkong which was collected from Northern and Eastern of Thailand were extracted by the hot and cold processes using water, chloroform, and methanol. The extracts were tested for anti-oxidative activities and anti-proliferation as well as matrix metalloproteinase inhibition on KB cells.

Results: The hot water extract of seeds from Northern region (NSEWH), the cold water extract of old leaves from Northern region (NOLWC), and the hot chloroform extract of young leaves from Eastern region (EYLCH) showed the highest free radical scavenging, metal ion chelating, and lipid peroxidation inhibition with SC₅₀, MC₅₀ and IPC₅₀ values of 0.34?±?0.03, 0.47?±?1.60 and 0.86?±?0.31?mg/ml, respectively. The hot and cold chloroform extract of young fruits from Northern region (NYFCH and NYFCC) exhibited anti-proliferation effect against KB cells with IC₅₀ values of 603.45?±?55.35 and 765.06?±?46.19?mg/ml, respectively. NYFCC exhibited the highest pro- and active MMP-2 inhibition at 53.03?±?2.65 and 31.30?±?0.43%, more than all tested standard anticancer drugs except cisplatin.

Discussion and conclusion: The cold chloroform extract of young fruits from Northern region appeared to contain anticancer active compounds against KB cells because of its high anti-proliferation and MMP-2 inhibition activities.     

Delivery of atovaquone and proguanil across sublingual membranes,in vitro

Malarone^?, a combination of atovaquone (AT) and proguanil (PR), is indicated for the prophylaxis and treatment of uncomplicated Plasmodium falciparum malaria. This study aimed to determine in vitro the feasibility of delivering the combination of AT and PR as a spray formulation via the sublingual route, using Franz diffusion cells incorporating porcine sublingual mucosa. Firstly, 1?mg mL^?1 of each drug in 20% 1,8-Cineole in ethanol was used; and secondly, 5?mg mL^?1 AT and 1?mg mL^?1 PR in 20% 1-methyl-2-pyrrolidone in ethanol was examined, dosed every 2?h over a 12-h period and receptor phase samples were analyzed by HPLC. From the first study, mean fluxes for AT and PR were 12.89?±?1.2 and 5.88?±?0.9 µg cm^?2 h^?1 respectively; pharmacokinetic calculations indicated that these fluxes were insufficient to achieve the target plasma concentrations for AT and PR of 1.4 µg mL^?1 and 200?ng mL^?1 respectively, in the treatment of falciparum malaria. However, in the second study, the fluxes of AT and PR increased to 50.92?±?20.8 and 12.01?±?1.5 µg cm^?2 h^?1 respectively, and pharmacokinetic calculations indicated that therapeutic plasma concentrations are attainable for pediatric application.     

The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study

Abstract

Context: Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown.

Objective: We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels.

Methods: Thirty-two adults (25.9?±?6.6 years) were exposed to coarse CAP (76.2?±?51.5?μg?m^?3) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n?=?21), white blood cell (n?=?24) and vascular endothelial growth factor (VEGF) (n?=?16–19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests.

Results: Circulating EPC levels were elevated 2 [108.29 (6.24–249.71) EPC?mL^?1; median (25th–75th percentiles), p?=?0.052] and 20 h [106.86 (52.91–278.35) EPC?mL^?1, p?=?0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00–84.83) and 50.16 (0.00–104.79) EPC?mL^?1]. VEGF and white blood cell (WBC) levels did not differ between exposures.

Conclusions: Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute “endothelial injury” and/or a circulating EPC response to sympathetic nervous system activation.     

Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery

The purpose of the present study was to develop Tamoxifen loaded β-cyclodextrin nanosponges for oral drug delivery. The three types of Tamoxifen loaded β-cyclodextrin nanosponges were synthesized by varying the molar ratios of β-cyclodextrin to carbonyldiimidazole as a crosslinker viz. 1:2, 1:4 and 1:8. The Tamoxifen nanosponge complex (TNC) with particle size of 400–600?nm was obtained by freeze drying method. Differential scanning calorimetry, Fourier transformed infra-red spectroscopy and X-ray powder diffraction studies confirmed the complexation of Tamoxifen with cyclodextrin nanosponge. AUC and C_max of TNC formulation (1236.4?±?16.12 µg·mL^?1 h, 421.156?±?0.91 µg/mL) after gastric intubation were 1.44 fold and 1.38 fold higher than plain drug (856.079?±?15.18 µg·mL^?1 h, 298.532?±?1.15 µg/mL). Cytotoxic studies on MCF-7 cells showed that TNC formulation was more cytotoxic than plain Tamoxifen after 24 and 48?h of incubation.     

Bioactive compounds from endemic plants of Southwest Portugal: Inhibition of acetylcholinesterase and radical scavenging activities

Context: Natural products are reported to have substantial neuroprotective activity due to their radical scavenging capacity, and also acetylcholinesterase (AChE) inhibitory capacity, both activities important in neurodegeneration.

Objective: The undesirable side effects of compounds in pharmacological use make it important to identify natural neuroprotective molecules. This work assesses the potential of five endemic Portuguese plants as sources of neuroprotective compounds.

Materials and methods: Antioxidant capacity for peroxyl radical was determined by Oxygen Radical Absorbance Capacity method and for hydroxyl by Electron Paramagnetic Resonance, as well as AChE inhibitory capacity of the plant hydroethanolic extracts. The molecules responsible for these valuable properties were also tentatively identified by HPLC.

Results and discussion: Armeria rouyana and Thymus capitellatus presented some of the highest phenolic contents (76.60?±?7.19 and 12.82?±?0.24?mg GAE g^?1 dw, respectively) and antioxidant capacities (592?±?116 and 449?±?57 μmol TE g^?1 dw, respectively). The flavonoids were identified as the phytomolecules related to the antioxidant capacity of these plant extracts; in the case of A. rouyana, l-ascorbic acid also made an important contribution (3.27?±?0.26?mg g^?1 dw). Plant extracts clearly demonstrated effective AChE inhibitory activity (480?±?98 and 490?±?46 μg mL^?1, respectively), that could be associated to polyphenols.

Conclusions: The extracts of A. rouyana and T. capitellatus and their active components, especially polyphenols, demonstrate interesting neuroprotective potential. They, therefore, deserve further study as their phytomolecules are promising sources of either natural neuroprotective products and/or novel lead compounds.