Temperature-Sensitive Microemulsion Gel: An Effective Topical Delivery System for Simultaneous Delivery of Vitamins C and E

Microemulsions (ME)—nanostructured systems composed of water, oil, and surfactants—have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-like ME with temperature-sensitive rheological properties was formed. The temperature-driven changes in its microstructure were confirmed by rotational rheometry, viscosity measurements, and droplet size determination. The release studies have shown that the vitamins’ release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). According to effectiveness in skin delivery of both vitamins, o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer, indicating that no simple correlation between vitamins release and skin absorption could be found. The cytotoxicity studies revealed good cell viability after exposure to ME and confirmed all tested microemulsions as nonirritant. This work was supported by a grant of Slovenian Research Agency.     

Amino acids and protein profile in floral nectar: Much more than a simple reward

Nectar is considered a primary alimentary reward for a large variety of pollinators. Recent studies demonstrated that nectar may have other functions in addition to attracting pollinators. Mainly other two functions have been recognized: defense against microbial invasion and post-secretion modification of sugar profile. The floral nectar of Cucurbita pepo L. has been analyzed to confirm the presence of defense proteins, namely xylosidases that were identified by means of a proteomic approach in a previous study. An enzyme assay was also performed that revealed low invertase activity for which the optimal pH was determined. This invertase activity is not able to modify the sugar profile significantly during the short period of anthesis (6 h). The amino acids complement of the nectar of both sexes was also determined. Sixteen of the 20 protein amino acids have been detected. Proline comprises more than 30% of total amino acid content in male and female flowers. Three non-protein amino acids (taurine, β-alanine, and GABA) represent almost one third of the total amino acid content, and of these, GABA is the most abundant (16%). Several biological activities were attributed to these amino acids and further studies are needed to assess their presumed involvement in managing the foraging behavior of insects. More recent studies, including our own, demonstrate that the various functions of nectar are much more complex than previously thought.     

Synthesis and investigation of the conversion reactions of pyrimidine‐thiones with nucleophilic reagent and evaluation of their acetylcholinesterase,carbonic anhydrase inhibition,and antioxidant activities

The conversion reactions of pyrimidine‐thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2‐epoxy propane, 1,2‐epoxy butane, and 4‐chlor‐1‐butanol and pyrimidine‐thiones. These pyrimidine‐thiones derivatives ( A–K ) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 ± 33.7–467.5 ± 126.9 nM. The hCA I and II were effectively inhibited by these compounds, with K_i values in the range of 4.3 ± 1.1–9.1 ± 2.7 nM for hCA I and 4.2 ± 1.1–14.1 ± 4.4 nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed K_i value of 13.9 ± 5.1 nM against hCA I and 18.1 ± 8.5 nM against hCA II. The antioxidant activity of the pyrimidine‐thiones derivatives ( A–K ) was investigated by using different in vitro antioxidant assays, including Cu²⁺ and Fe³⁺ reducing, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH^?) radical scavenging, and Fe²⁺ chelating activities.     

Synthesis of some novel pyridine compounds containing bis‐1,2,4‐triazole/thiosemicarbazide moiety and investigation of their antioxidant properties,carbonic anhydrase,and acetylcholinesterase enzymes inhibition profiles

Some novel derivatives of thiosemicarbazide and 1,2,4‐triazole‐3‐thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine‐2,5‐dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine‐2,5‐dicarboxylate ( 1 ). The reaction of dimethyl‐2,5‐pyridinedicarboxylate ( 1 ) with hydrazine hydrate good yielded pyridine‐2,5‐dicarbohydrazide ( 2 ). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3–8 h afforded 1,4‐disubstituted thiosemicarbazides ( 3a–e ). Base‐catalyzed intra‐molecular dehydrative cyclization of these intermediates furnished the 4,5‐disubstituted bis‐mercaptotriazoles ( 4a–e ) in good yield (85%–95%). Among the target compounds, 2,2′‐(pyridine‐2,5‐diyldicarbonyl)bis[N‐(p‐methoxyphenyl)hydrazinecarbothioamide] ( 3c ) showed very high activity with value of 72.93% against 1,1‐diphenyl‐2‐picrylhydrazyl free radical at the concentration of 25 μg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with K_is in the range of 3.07 ± 0.76–87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37–10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57–7.66 ± 2.06 nM against hCA II, respectively.     

Much more than a ratio: multivariate selection on female bodies

Studies of the attractiveness of female bodies have focussed strongly on the waist, hips and bust, but sexual selection operates on whole phenotypes rather than the relative proportions of just two or three body parts. Here, we use body scanners to extract computer‐generated images of 96 Chinese women’s bodies with all traits unrelated to body shape removed. We first show that Chinese and Australian men and women rate the attractiveness of these bodies the same. We then statistically explore the roles of age, body weight and a range of length and girth measures on ratings of attractiveness. Last, we use nonlinear selection analysis, a statistical approach developed by evolutionary biologists to explore the interacting effects of suites of traits on fitness, to study how body traits interact to determine attractiveness. Established proxies of adiposity and reproductive value, including age, body mass index and waist‐to‐hip ratio, were all correlated with attractiveness. Nonlinear response surface methods using the original traits consistently outperform all of these indices and ratios, suggesting that indices of youth and abdominal adiposity tell only part of the story of body attractiveness. In particular, our findings draw attention to the importance of integration between abdominal measures, including the bust, and the length and girth of limbs. Our results provide the most comprehensive analysis to date of the effect of body shape and fat deposition on female attractiveness.     

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation

In the present study, coumarin‐bearing three pyridinium and three tetra‐alkyl ammonium salts were synthesized. The compounds were fully characterized by ¹H‐ and ¹³C‐NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco‐2) and non‐cancer mouse fibroblast (L‐929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.     

The old world salsola as a source of valuable secondary metabolites endowed with diverse pharmacological activities: a review

Salsola is an important genus in the plant kingdom with diverse traditional, industrial, and environmental applications. Salsola species are widely distributed in temperate regions and represent about 45% of desert plants. They are a rich source of diverse phytochemical classes, such as alkaloids, cardenolides, triterpenoids, coumarins, flavonoids, isoflavonoids, and phenolic acids. Salsola spp. were traditionally used as antihypertensive, anti-inflammatory, and immunostimulants. They attracted great interest from researchers as several pharmacological activities were reported, including analgesic, antipyretic, antioxidant, cytotoxic, hepatoprotective, contraceptive, antidiabetic, neuroprotective, and antimicrobial activities. Genus Salsola is one of the most notorious plant genera from the taxonomical point of view. Our study represents a comprehensive review of the previous phytochemical and biological research on the old world Salsola secies. It is designed to be a guide for future research on different plant species that still belong to this genus or have been transferred to other genera.     

Chitosan-reduced gold nanoparticles: a novel carrier for the preparation of spray-dried liposomes for topical delivery

Exposure of skin to various chemical and physical agents results in excessive stress to the outermost cell layer of the skin, causing different degenerative effects that can be minimized by using antioxidant formulations. The major challenge, in this regard, is to develop a formulation, which can prevent photodegradation of the actives, thus allowing a significant amount to be deposited at the site. In recent decades, liposomal formulations have been extensively employed to overcome the barrier properties of the skin and photodegradation of actives. In the present study, chitosan-reduced gold nanoparticles were investigated for its potential as a carrier to prepare liposomes by a spray-drying method. Liposomes so obtained were characterized for phospholipid recovery, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, particle size, zeta potential, encapsulation efficiency, and deposition of drug and gold nanoparticles in the rat skin. Further, a liposomal gel formulation was prepared using Carbopol^® 980 NF (Noveon Systems, Kochi, India) and evaluated for drug deposition in the skin. Antioxidant activity of vitamin C encapsulated in gold liposomes was determined on a human leukemia (HL-60) cell line. The use of gold nanoparticles as a carrier showed improved phospholipid recovery and thus overcomes the liposome scalability problem. DRIFT spectra confirmed the presence of phospholipid in the formulation. Liposomal gel showed improved drug deposition, as compared to control and marketed preparations. A more interesting contribution of the chitosan-reduced gold nanoparticles was an enhanced antioxidant activity seen in case of the vitamin C–loaded gold liposomal formulation. Liposomal formulation was found to be stable for 3 months at 30°C and 65% relative humidity.     

Mushroom Species Stereum hirsutum as Natural Source of Phenolics and Fatty Acids as Antioxidants and Acetylcholinesterase Inhibitors

Many lignicolous mushroom species are used as a food supplement and may represent an alternative treatment of Alzheimer's disease (AD). This study aimed to evaluate acetylcholinesterase inhibition (AChEI) of Stereum hirsutum together with antioxidant activity (AO) and cytotoxic activity against HepG2 cells. Different extracts (water, ethanol, methanol, polysaccharide) were analyzed, with respect to their mineral composition and chemical content. Ethanol extract was the most potent in AChEI (98.44 %) and demonstrated cytotoxic activity (91.96 % at 900.00 μg/mL), while the highest AO was demonstrated for polar extracts (methanol and water) as well. These activities may be attributed to determined phenolics (hydroxybenzoic and quinic acid) and fatty acids (FA), while biflavonoid amentoflavone may be responsible for cytotoxic activity. The most prevalent FA was linoleic (40.00 %) and the domination of unsaturated FA (UFA) (71.91 %) over saturated (26.96 %) was observed. This is the first report of AChEI of S. hirsutum extracts and first detection of amentoflavone. Due to high amount of UFA and well-expressed AChEI, this species can be considered as a potent food supplement in the palliative therapy of AD.     

Smoking among shift workers: More than a confounding factor

In studies on the cardiovascular disease risk among shift workers, smoking is considered to be a confounding factor. In a study of 239 shift and 157 daytime workers, it was found that shift work was prospectively related to increased cigarette consumption, indicating that smoking might be in the causative pathway; however, the number of study subjects was too low to warrant sound conclusions. Therefore, data from the Maastricht Cohort study were used to investigate the longitudinal relation between smoking and shift work in a much larger population. In this study, a total of 12,140 employees were followed for two years by means of self-administered questionnaires. The authors compared workers who normally worked during daytime hours only (74%) with those who worked other than day shifts (26%). Logistic regression analyses were performed, adjusting for demographic factors of age, gender, and educational level to evaluate the risk of starting to smoke (n=25) in the group of non-smoking workers and the risk of quitting (n=318) in the group of smoking workers. Logistic regression analysis showed a significant association between shift work and taking up smoking during the two-year follow-up (odds ratio: 1.46, p=0.03). The risk to stop smoking was somewhat lower in shift workers (odds ratio: 0.91) but not statistically significant (p=0.5). To conclude, this study showed that, independent of educational level, shift workers are more prone to start smoking. This finding might have important implications for studies on the health effects of shift workers and for possible interventions aimed at the reduction of the excess health risk among shift workers.     

GC/MS Profiling,In Vitro and In Silico Pharmacological Screening and Principal Component Analysis of Essential Oils from Three Exotic and Two Endemic Plants from Mauritius

The chemical and pharmacological profiles of essential oils (EOs) hydrodistilled in yields of 0.03–0.77 % (w/w) from three exotic (Cinnamomum camphora, Petroselinum crispum, and Syzygium samarangense) and two endemic (Pittosporum senacia subsp. senacia and Syzygium coriaceum) medicinal plants were studied. GC-MS/GC-FID analysis of the EOs identified the most dominant components to be myristicin (40.3 %), myrcene (62.2 %), 1,8-cineole (54.0 %), β-pinene (21.3 %) and (E)-β-ocimene (24.4 %) in P. crispum, P. senacia and C. camphora, S. samarangense and S. coriaceum EOs, respectively. All EOs were found to possess anti-amylase (0.70–1.50 mM ACAE/g EO) and anti-tyrosinase (109.35–158.23 mg KAE/g) properties, whereas no glucosidase inhibition was displayed. Only Syzygium EOs acted as dual inhibitors of both acetyl- and butyryl-cholinesterases, while P. senacia and C. camphora EOs inhibited acetylcholinesterase selectively and P. crispum EO was inactive (AChE: 4.64–4.96 mg GALAE/g; BChE: 5.96 and 7.10 mg GALAE/g). Molecular docking revealed 1,8-cineole to present the best binding affinities with butyrylcholinesterase, amylase and tyrosinase, while both myristicin and β-pinene with acetylcholinesterase and finally β-pinene with glucosidase. In vitro antioxidant potency was also demonstrated in different assays (DPPH: 13.52–53.91 mg TE/g, ABTS: 5.49–75.62 mg TE/g; CUPRAC: 45.38–243.21 mg TE/g, FRAP: 42.49–110.64 mg TE/g; and phosphomolybdenum assay: 82.61–160.93 mM TE/g). Principal component analysis revealed the EOs to differ greatly in their bioactivities due to their chemodiversity. This study has unveiled some interesting preliminary pharmacological profiles of the EOs that could be explored for their potential applications as phytotherapeutics.     

Microemulsion for topical delivery of fenoprofen calcium: in vitro and in vivo evaluation

The aim of this study was to investigate microemulsion (ME) based topical delivery system for fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. ME was prepared by the water titration method using oleic acid as oil phase, tween 80 as a surfactant and propylene glycol as a cosurfactant. Oleic acid was selected as oil phase due to its good solubilizing capacity. ME existence region was determined using pseudo-ternary phase diagrams for preparing different formulations. Six different formulations were selected with various values of oil (25–68%), water (2–3%), and the mixture of surfactant and cosurfactant (1:1) (24–67%). The selected ME formulae were characterized for optical birefringence, transmission electron microscopy (TEM), pH, % transmittance, electronic conductivity, drug content, droplet size, rheological properties and stability evaluation. In vitro release study of FPCa from ME s through the synthetic membrane and hairless rat skin were evaluated. The optimized formula ME5 consisting of 5% w/w FPCa, 60% w/w oleic acid as oil phase, 3% w/w aqueous phase, and 32% w/w of surfactant phase containing Tween 80 and propylene glycol (1:?1) showed the highest transdermal flux and highest skin permeation rate. Finally, the % inhibition of carrageenan-induced rat paw edema of the optimized formula ME5 was highly significant (p?0.001) as compared to plain gel of FPCa. In conclusion, ME is a promising technique for topical delivery of FPCa.     

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

A new synthetic pathway was devised to reach tetrasubstituted 3-arylthiophene 2-carboxylic acids in a three-step solid-phase synthesis. This very efficient methodology provided more than 20 new compounds that were evaluated for their ability to inhibit protein farnesyltransferase from different species as well as Trypanosoma brucei and Plasmodium falciparum proliferation.     

重金属在拟水狼蛛体内的分布及对其体内抗氧化酶活性的影响

为了探明重金属在拟水狼蛛Pirata subpiraticus体内的分布及对其体内抗氧化酶活性的影响,本研究于2009年6月在河南南阳地区5种不同生境下,共采集50份土壤样本和300头拟水狼蛛样本,采用原子吸收光谱法测定了5种不同生境下雄雌拟水狼蛛体内重金属的分布、GSH含量以及GST,CAT和SOD的活性。结果表明：5个采集样点（S1, S2, S3, S4和S5） 拟水狼蛛体内重金属（Cd,Pb,Cu和Zn）的含量差异显著（P<0.05）。同一地点拟水狼蛛体内重金属（Cd,Pb,Cu和Zn）的含量不同身体部位差异显著（P<0.05）,头胸部>足部>腹部,同一地点雄性拟水狼蛛重金属含量显著高于雌性（P<0.05）。在重金属胁迫下,重金属含量高（S1,S2,S3和S4）的拟水狼蛛体内GSH 含量显著高于参照组（S5）,雄性GSH 含量高于雌性（P<0.05）。对于不同身体部位,GSH 含量差异显著,头胸部GSH 含量最高,其次为足部,腹部含量最低;GSH 含量与重金属含量显著正相关（r2=0.9854,P<0.05）。对于GST,CAT和SOD,重金属含量高则酶活性低,雄性酶活性显著低于雌性,不同身体部位酶活差异不显著;GST,CAT和SOD酶活性与重金属（Cd和Pb或者Pb）含量显著负相关。因此检测拟水狼蛛不同身体部位的酶活性变化就可知环境中重金属的污染程度,拟水狼蛛可以作为重金属污染的重要监测指示生物。     

Chemical modification of hyaluronidase as a means to regulate its inhibition by heparin

The modification of hyaluronidase by aldehydodextran regulates inhibition of the enzyme by heparin. A 70–90% modification of the surface amino groups of hyaluronidase results in sharp conformational changes and a substantial decrease of its inhibition by heparin, whereas hyaluronidase derivatives with a modification degree of 96–100% are practically uninhibited.     

Rosmarinus officinalis L. essential oils from Spain: composition,antioxidant capacity,lipoxygenase and acetylcholinesterase inhibitory capacities,and antimicrobial activities

Abstract

Six Rosmarinus officinalis L. essential oils (RoEOs) from Murcia (Spain) were studied using gas chromatography. Analysis of their relative and absolute composition showed 1,8-cineole, camphor, α-pinene and camphene to be the main compounds. Moreover, enantioselective gas chromatographies showed different enantiomeric ratios of camphor, limonene and borneol. The antioxidant and chelating capacities of RoEOs and their individual components were measured in an attempt to ascertain the cause of RoEO activity as a whole. All the essential oils were able to inhibit lipoxygenase activity due to bornyl acetate, camphor, terpinen-4-ol and 1,8-cineole and acetylcholinesterase activity due to 3-carene and 1,8-cineole, mainly. When the antimicrobial activities were tested against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans, the least sensitive microorganism was P. aeruginosa and the most sensitive C. albicans. This study furthers our knowledge of six RoEOs from two chemotypes, all of which show potential for industrial applications.     

高温胁迫对筛豆龟蝽成虫抗氧化能力的影响

为探索筛豆龟蝽Megacopta cribraria (Fabricius)对高温的耐受性及其体内抗氧化系统对极端高温胁迫的响应机制.以25℃为对照温度,经高温37℃、40℃、43℃和46℃胁迫处理4h后,测定筛豆龟蝽成虫存活率及其体内超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、过氧化物酶(POD)的活性以及总抗氧化(T-AOC)能力和丙二醛(MDA)含量的变化.在37℃～46℃高温胁迫下,筛豆龟蝽成虫存活率与对照无显著差异,其体内SOD和CAT活性较对照组均显著增加,其中,SOD活性在37℃最高,随着温度进一步升高,其活性有所下降,但仍显著高于对照.CAT一直保持较高活性,随着处理温度的升高CAT活性呈逐渐升高趋势,在极端高温46℃时其活性最高.POD活性在37℃～ 40℃显著高于对照,43℃和46℃处理与对照无显著差异.T-AOC活性在各处理温度下均显著高于对照,且随着处理温度的升高T-AOC活性呈先升高后降低趋势.各处理MDA含量与对照无显著差异.筛豆龟蝽体内3种抗氧化酶的活力、总抗氧化能力和MDA在适应高温胁迫过程中发挥了重要作用.     

Functional constituents of wild and cultivated Goji (L. barbarum L.) leaves: phytochemical characterization,biological profile,and computational studies

Goji (Lycium barbarum L.) leaves are emphasized as a functional tea or as dietary supplements. The phenolic compound profile, antioxidant, enzyme inhibitory, antimicrobial, and antimutagenic activities of leaf extracts from two selected cultivars in comparison with wild-growing plants have been evaluated. HPLC-DAD/ESI-ToF-MS analysis revealed the presence of phenolic acids and flavonoids with chlorogenic acid and rutin being the dominant compounds in the cultivated plants, whereas rutin and kaempeferol-3-O-rutinoside for wild growing ones. In particular, cv. Erma contained the highest amount of chlorogenic acid and showed a strong tyrosinase-inhibitory effect. Staphylococcus aureus, Listeria monocytogenes, and Penicillium funiculosum were the most sensitive strains when exposed to extracts from cultivated plants. Antimutagenic activity was evaluated by Ames' test. The tested extracts provided high protection against mutagenicity induced by 2-anthramine (2-AA) to Salmonella typhimurium strains TA 98 and TA 100 (max. inhibition (%) 88% and 74.2%, respectively). Overall, Goji leaves are a rich source of bioactive compounds with functional properties that need further risk/benefit evaluation when used in foods or health-promoting formulations.