Effects of Calendula officinalis and Capsicum annum glycolic extracts on planktonic cells and biofilms of multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa.

Empirical knowledge of natural plant extracts is increasingly proving to be a promising field. The effect of Calendula officinalis L. (CO) and Capsicum annum (CA) glycolic extracts (GlExt) have potential that should be further developed in microbial tests. The effect of CO-GlExt and CA-GlExt was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as collection strains for each bacterial. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined in comparison with 0.12% chlorhexidine. The tests were performed on single species biofilms, at 5 min and 24 h, using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The MIC and MBC of the extract ranged from 1.56 to 50 mg mL-1 for all strains evaluated. Analysis of the MTT assay revealed a strong antimicrobial potential of CA-GlExt, comparable to chlorhexidine. The findings suggest that CA-GlExt is effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic state and biofilms.

Cancer-Mitochondria Dual-Targeting Glycol/Ferrocenium-Based Polydopamine Nanoparticles for Synergistic Photothermal and Photodynamic Therapy.

A cancer-mitochondria dual-targeting nanoparticle based on lactose and ferrocenium derivatives conjugated polydopamine (PDA@Lac/Fc/Hyp) was constructed, which exhibited cancer-targeting and mitochondria-targeting ability deriving from lactose and ferrocenium derivatives due to the specific carbohydrate-protein interaction and cationic species properties, respectively. Moreover, PDA@Lac/Fc/Hyp showed great biocompatibility and phototherapeutic efficiency. This work displays a good example of constructing cancer-mitochondria dual-targeting nanoparticle for synergistic phototherapy.

Antiviral activity of different extracts of standardized propolis preparations against HSV.

BACKGROUND: Viral infections are among the most common problems in health-care practice. Natural products offer great promise as potentially effective antiviral drugs. Propolis is a honeybee product with biological properties and therapeutic applications. We aimed to investigate the antiviral activity of different extracts of Standardized Propolis Preparations (M.E.D.®) with glycol, ethanol, glycerol and soya oil, against herpes simplex type-1 (HSV-1) and type 2 (HSV-2) viruses. METHODS: Chemical composition and antiviral activity of each extract were determined. The selective index (SI=CC50/EC50) was determined as a parameter to indicate the in vitro antiviral activity of the extracts compared with acyclovir as the control. RESULTS: SI values of glycol, ethanol, glycerol, soya oil extracts and acyclovir were determined as 6.8, 4.1, 2.2, 3.3 and 6.3 against HSV-1, and as 6.4, 7.7, 1.9, 4.2 and 2.9 against HSV-2, respectively. Glycolic propolis extract was found to possess a greater antiviral activity than acyclovir for both HSV-1 and 2, while glycolic, ethanolic and soya oil preparations were found to have more significant activity than acyclovir for HSV-2. CONCLUSIONS: It was determined that standardized propolis preparations have antiviral bioactivity against HSV.

The anti-inflammatory and antioxidant properties of 1,2-decanediol and willow bark extract in lipopolysaccharide-stimulated keratinocytes.

BACKGROUND: 1,2-Decanediol (S-Mal) is an organic compound belonging to the 1,2-alkanediol family, with two hydroxyl groups located on the first and second carbon of the alkane chain, probably responsible for the enhanced anti-bacterial efficacy. The willow bark total extract (W-Mal) has been used since thousands of years as an herbal remedy for its antipyretic, analgesic, anti-inflammatory and anti-microbial activities. S-Mal is used in cosmetic preparations, whether W-Mal can be topically or systemically administered. Aim of our study was to evaluate in vitro the anti-inflammatory and antioxidant properties of S-Mal and W-Mal, singularly or in combination, in LPS-stimulated keratinocytes. METHODS: The possible toxic effect of S-Mal and W-Mal was assessed through analysis of cell viability 24 hours after treatment. The anti-inflammatory and antioxidant activities were evaluated by measuring IL-8, TNF-α and IL-1ß production as well as cellular antioxidants (GSH and NADPH) consumption, 24 and 48 hours, respectively, after LPS stimulation. RESULTS: Both substances resulted able to: 1) increase cell viability (P<0.05); 2) decrease the release of inflammatory mediators (IL-8, TNF-α and IL-1ß) (P<0.05 - P<0.001); and 3) limit the depletion of cellular antioxidants (GSH and NADPH) (P<0.001). CONCLUSIONS: S-Mal and W-Mal have shown a potential cytoprotective activity when used together, and good anti-inflammatory and antioxidant effects when used either singularly or in combination. In light of our results, S-Mal and W-Mal could represent effective and safe options in the management of bacterial-induced or aggravated skin conditions.

[Identification and preparation of a glycol-protein fraction AN from tea extracts and its in vivo and in vitro anti-hyperglycosemia activity].

The present study compared active ingredients of tea from different sources to select tea type and the fraction of tea extracts for the highest anti-hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected tea extract. Tea extracts were separated and enriched by molecular weight using ultra-filtration technology. The extracts were first screened by α-glucosidase inhibition assay, followed by using a rat inverted intestine sac system to measure the effect on glucose transport. Both alloxan-induced diabetic rat model and high-fat diet combined with streptozotocin-induced rat diabetes mellitus model were used to study the effects of active components on blood glucose, body weight, insulin resistance. The experimental results showed that the different kinds of tea extracts had different inhibitory effects on α-glucosidase, and the inhibitory effect of tea extract E on α-glucosidase was stronger. The effects of different components of tea extract E also varied greatly, of which Fraction AN protein had stronger inhibitory effect on α-glucosidase than other fragments, and Fraction AN protein had a strong inhibitory effect on glucose transport, reduced blood sugar and normalized insulin secretion in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the extracts might be responsible for the anti-hyperglycemic activity of tea polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on both α-glucosidase activity and glucose transport by the small intestine. It also reduced blood glucose level and normalized insulin secretion in diabetic rats, and has a protective effect on diabetic rats.

Pleiotropic Effects of White Willow Bark and 1,2-Decanediol on Human Adult Keratinocytes.

BACKGROUND: Acne vulgaris is a common skin defect, usually occurring during adolescence, but often it can persist in adults leaving permanent face scarring. Acne is usually treated with topical drugs, oral antibiotics, retinoids, and hormonal therapies, but medicinal plants are increasingly employed. OBJECTIVE: To investigate the protective role of white willow bark (WWB) and 1,2-decanediol (DD) on the damage caused by lipopolysaccharides (LPS) on human adult keratinocytes (HaCaT). METHODS: HaCaT were exposed to LPS alone or in association with WWB and DD. Epidermal viability, metabolic modulation, inflammatory activity, and cell migration were assessed with both common standardized protocols or high-throughput screening systems. RESULTS: The preincubation of HaCaT with WWB and DD (used separately or in combination) differently prevented the alterations induced by LPS on HaCaT in terms of growth factor release (IGF, EGF, VEGF), cytokine production (IL-1α, IL-6, IL-8), or expression of the transcription factor FOXO-I. Moreover, they partially restore wound repair lowered by LPS. CONCLUSIONS: These results suggest that both natural compounds were able to differently affect several functions of LPS-stressed keratinocytes suggesting their potential role for the prevention of acne vulgaris, without adverse effects.

Activity of alkanediol alkanoates against pathogenic plant fungi Rhizoctonia solani and Sclerotium rolfsii.

Thirty known dialkanoates of ethylene, propylene and diethylene glycols were synthesized by reacting the glycols with acyl chlorides and their structures confirmed by IR, NMR and mass spectral analyses. They exhibited significant antifungal activity against two phytopathogenic fungi Rhizoctonia solani Kuehn and Sclerotium rolfsii Sacc in a dose dependent manner. Propylene glycol dipentanoate was the most active against R. solani. followed by diethylene glycol dibutanoate and ethylene glycol dibutanoate. Against S. rolfsii ethylene glycol diheptanoate was found to be most active followed by diethylene glycol diisobutanoate As compared to the standard reference benomyl (EC50 5.16 microg/mL), the potential alkanediol dialkanoates showed EC50 in the range of 33 - 60 microg/mL.

Antimicrobial polyacetylenes from Panax ginseng hairy root culture.

Two new polyacetylenes, 1-hydroxydihydropanaxacol (3) and 17-hydroxypanaxacol (4), were isolated from Panax ginseng hairy root culture, along with dihydropanaxacol (1), panaxacol (2) and ginsenoyne D (5). Highly hydroxylated compounds 1-4 were isolated from the medium and compound 5, which was a biosynthetic precursor of compound 1, was isolated from the roots. Compounds 1-4 showed antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Cryptococcus neoformans and Aspergillus fumigatus. It is suggested that P. ginseng plants release antimicrobial polyacetylenes into the surrounding soil from the roots as defense compounds.

Properties of a new mouthrinse for patients receiving radiation therapy.

INTRODUCTION: Patients receiving radiation therapy due to oral cancer develop complications such as hyposalivation, mucositis, oral infections, dental hypersensitivity and caries. Mouthrinses can alleviate some of these problems. AIMS AND OBJECTIVES: To investigate the in vitro antimicrobial properties and cytotoxicity of an experimental mouthrinse. METHODS: The mouthrinse contained 30% hexylene glycol (glycerine), 7% potassium nitrate and 0.025% sodium fluoride. The minimal inhibitory concentration (MIC) of these ingredients and the mixture was determined for C. albicans, S. aureus and S. mutans over 24 hours at different concentrations. The MICs of two commercial mouthrinses, Corsodyl and Plax, were also determined using the same organisms. All mouthrinses were then tested to determine the percentage kill over 1, 2, and 3 minutes. RESULTS: The MICs for hexylene glycol were 10%, 30% and 10% for C. albicans, S. aureus and S. mutons respectively. Potassium nitrate and sodium fluoride had no antimicrobial effects. The MIC of Corsodyl was 0.016 mg/ml for all the test organisms. The MIC for Plax varied from 0.0002 mg/ml to 0.001 mg/ml. The kill rates for all mouthrinses were acceptable, with no statistical differences between them. The experimental mouthrinse was not toxic to human oesophageal SCC cells after 1 minute exposure. At the time of the experiment, the costs of a similar quantity of the experimental mouthrinse, Corsodyl and Plax were R5.24, R30.00 and R10.00 respectively. CONCLUSIONS: The experimental mouthrinse was cost-effective and proved to have an antimicrobial effect and could be used safely to alleviate oral infections, desensitize teeth, improve oral hygiene and control dental caries in cancer patients after radiation therapy.

Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice.

BACKGROUND AND PURPOSE: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4'-[[pentanoyl (phenyl) amino]methyl]-1,1'-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). EXPERIMENTAL APPROACH: A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. KEY RESULTS: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose-response curve for compound A showed peaks at around 0.005-0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT(2) receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. CONCLUSIONS AND IMPLICATIONS: Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists.

Sizing particles of natural uranium and nuclear fuels using poly-allyl-diglycol carbonate autoradiography.

Theoretical and experimental methods were developed to assess the size distribution of alpha-emitting particles captured on air-sampler filters. The particle size of oxides of low enriched, depleted and natural uranium and also aged plutonium in mixed oxide reactor fuels of known composition was determined using poly-allyl-diglycol carbonate (PADC) autoradiography, the commercial product TASTRAK((R)), solid-state nuclear track detectors. The exposed PADC was chemically etched to reveal clusters of tracks, radially dispersing from central points. A theoretical model was developed which converted the number of tracks in a track cluster to the hot particle diameter. The diameters of 26 particles of natural uranium oxide were measured (4-130 microm) using an optical microscope. There was a good agreement between these particle size measurements and a theoretical assessment based on the track cluster count.

Development and biopharmaceutical evaluation of quinupramine-EVA matrix containing penetration enhancer for the enhanced transdermal absorption in rats.

To increase the skin permeation of quinupramine through the rat skin, different types of enhancers were added to an ethylene-vinyl acetate (EVA) matrix containing 2% quinupramine. The effects of the enhancers on the level of quinupramine permeation through the skin were evaluated by using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, which included fatty acids (saturated and unsaturated), glycerides, pyrrolidones, and nonionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The pharmacokinetics and bioavailability of quinupramine from an EVA matrix were examined to determine the level of percutaneous absorption in rats. The percutaneous absorption of quinupramine from the EVA matrix with or without an enhancer was investigated. Quinupramine was administered orally or intravenously to compare the pharmacokinetic parameters with that of the transdermal route. The relative bioavailability of quinupramine in the matrix containing polyoxyethylene-2-oleyl ether as an enhancer was approximately 2.81 times higher than the group without an enhancer. Histological examination revealed that the skin pretreated with the EVA matrix containing the enhancers had a loosely layered stratum corneum. These results show that the quinupramine-EVA matrix containing a permeation enhancer could be a good transdermal delivery system for providing sustained plasma concentrations.

Preparation and evaluation of bioadhesive benzocaine gels for enhanced local anesthetic effects.

This study was performed to develop new enhanced anesthetic benzocaine gels with a suitable bioadhesive property for local anesthetic effects. As the concentration of benzocaine in the HPMC gels increased up to 15%, the permeation of drug increased, thereafter slightly increased. The activation energy of drug permeation was 11.29 kcal/mol. Bioadhesive forces were also measured. The permeation rate of drug through the skin was studied using various enhancers, such as glycols, non-ionic surfactants or fatty acids. Among the enhancers used, diethylene glycol showed the most enhancing effects. Analgesic activity was examined using a tail-flick analgesimeter. According to the rat tail-flick test, the value of AUEC (0 - 360min) of 15% benzocaine gels containing diethylene glycol was 4662 +/- 200 s min, while that of gels without diethylene glycol was 3353 +/- 132 s min, showing about 1.39-fold increase in analgesic activity. Fifteen percentage of benzocaine gels containing diethylene glycol showed the most enhanced, prolonged analgesic effects, showing the maximum anesthetic effects at 240 min, while the gels without diethylene glycol showed maximum effect at 180 min.

Modulation of leukotriene B4 receptor-1 expression by dexamethasone: potential mechanism for enhanced neutrophil survival.

Glucocorticoids can down-regulate many inflammatory and immune responses and constitute a powerful therapeutic tool in a number of diseases. However, they have a somewhat paradoxical effect on neutrophils, in that they prolong their survival. Because leukotriene B(4) (LTB(4)) can also extend neutrophil survival, we proposed that glucocorticoids could prevent neutrophil apoptosis by up-regulating their expression of the high-affinity LTB(4) receptor (BLT1). Here we show that, indeed, dexamethasone (DEX) up-regulates the steady-state levels of BLT1 mRNA in human neutrophils. The effect was time and concentration dependent, being maximal at 4 h and at 10-100 nM DEX. The effect was also dependent on transcriptional activity, whereas BLT1 mRNA stability was not affected. DEX-induced up-regulation of BLT1 expression was prevented by pretreatment with the LTB(4) antagonist LY255283. Moreover, LTB(4) itself up-regulated the expression of BLT1 mRNA. BLT1 protein expression on neutrophils exposed to DEX for 24 h was also up-regulated 2- to 3-fold, and DEX-treated as well as LTB(4)-treated cells showed enhanced responsiveness to LTB(4) in terms of intracellular Ca(2+) mobilization and chemotaxis. Whereas DEX and LTB(4) alone decreased neutrophil apoptosis by approximately 50%, neutrophils treated with both LTB(4) and DEX showed >90% survival at 24 h. Moreover, BLT1 antagonists prevented the increased neutrophil survival induced by DEX as well as by LTB(4). Taken together, our results suggest that DEX-induced up-regulation of BLT1 expression in neutrophils may be one mechanism through which glucocorticoids can prolong neutrophil survival, namely by enhancing cell responses to the antiapoptotic effect of LTB(4).

Studies on the resistance of activated sludge bacteria to high concentrations of methanol, butanol, glycol, cyclohexanone and cyclohexylamine.

The resistance of bacterial strains isolated from activated sludge purifying petrochemical wastewaters to high concentrations of methanol, butanol, glycol, cyclohexanone and cyclohexylamine was examined. The strains were found to be resistant to up to 5000 mg/l of methanol, butanol and glycol. Cyclohexylamine in concentration 1500 mg/l completely inhibited the growth of all examined strains whereas cyclohexanone even at concentration 4500 mg/l eliminated only about half of the isolated strains. The highest resistance to cyclohexane derivatives was shown by bacteria belonging to Pseudomonas III. None of the studied strains was, however, able to utilize cyclohexanone and cyclohexylamine as a source of barbon and energy.

The antimycotic activity in vitro of five diols.

The antimycotic activity of ethane-1,2-diol, propane-1,2-diol, butane-1,3-diol, pentane-1,5-diol, and hexane-2,5-diol in vitro against Pityrosporum orbiculare, Candida albicans, Trichophyton rubrum, T. mentagrophytes var. interdigitale and Epidermophyton floccosum was studied. Ethane-1,2-diol had the lowest activity (MIC of 40-100 g 1(-1)), and hexane-2,5-diol the highest activity (MIC of 10-40 g 1(-1)). Among, the higher diols there can be both effective antifungal agents and substances with a lower risk of allergic and irritative skin reactions than propane-1,2-diol.

The importance of the "bay region" diol-epoxide in 7,12-dimethylbenz[a]anthracene skin tumor initiation and mutagenesis.

The skin tumor-initiating and V79 mutagenic activities of various derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) were investigated to determine what possible cellular metabolite(s) may be responsible for its carcinogenicity and/or mutagenicity. 1-,2-,3-,4- and 5-hydroxyDMBA were found to be essentially inactive as skin tumor initiators whereas 9- and 10-hydroxyDMBA had weak activity. The (+/-)-trans DMBA 8,9- and 5,6-dihydrodiols were also essentially inactive as skin tumor initiators and (+/-)-DMBA 8beta,9alpha-diol-10alpha-11alpha-epoxide had weak skin tumor initiating activity. All of the above tested derivatives of DMBA were essentially inactive as mutagens in the cell-mediated or direct V79 mutagenesis systems. A methyl or fluoro addition to the 1, 2 or 5 positions almost completely blocked the skin tumor initiating and V79 mutagenic activities of DMBA, whereas a fluoro addition to position 11 did not. From our data we suggest that a 'bay region' diol-epoxide may be important in DMBA carcinogenicity and mutagenicity.