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Docosanol is the only US Food and Drug Administration (FDA) approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis. Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products. A gas chromatography/selected ion monitoring mode mass spectrometry (GC/SIM-MS) method was developed and validated for docosanol determination in biological samples. Docosanol and isopropyl palmitate (internal standard) were separated on a high-polarity GC capillary column with (88% cyanopropyl)aryl-polysiloxane employed as the stationary phase. The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate, respectively; the total run time was 20 min. The GC/SIM-MS method was validated in accordance with USFDA guidelines, and the results met the USFDA acceptance criteria. The docosanol calibration standards were linear in the 100–10000 ng/mL concentration range (R2 > 0.994). The recoveries for docosanol from the receptor fluid and skin homogenates were >93.2% and >95.8%, respectively. The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples. On applying Abreva® cream tube and Abreva® cream pump, the amount of docosanol that penetrated human cadaver skin at 48 h was 21.5 ± 7.01 and 24.0 ± 6.95 ng/mg, respectively. Accordingly, we concluded that the validated GC/SIM-MS was sensitive, specific, and suitable for quantifying docosanol as a quality control tool. This method can be used for routine analysis as a cost-effective alternative to other techniques.

Some studies state that curcumin analog compounds can improve the bioavailability and biological activity of curcumin. One of the methods to predict the bioactivity of curcumin was computational using molecular docking method. This study has done bioactivity tests of curcumin analog compounds as antiviral using the molecular docking method with the software used are PLANTS, YASARA, MarvinSketch, and Pymol for visualization. This study used analog curcumin compounds derived from previous research. This study used five different viral reseptor types. The maraviroc, docosanol, ribavirin, and zanamivir were used as compound control in this research. The validated target protein consists of 5 (five) receptors with PDB codes 1V2I, 4WEG, 2HWI, 2QAD, and 3ALP. Based on this research, compounds that are predicted active as antiviral on each receptors that are: 2,5-bis(3,5-ditertbutyl-4-hydroxy benzyl)cyclopentanone (1V2I), 1,7- diphenyl-1,6-heptadiene-3,5-dione (4WEG), 1,7-bis(3,4-dibenzyloxiphenyl)-1,6-heptadiene-3,5-dione (2HWI), and 2,5-bis(3,5-ditertbutyl-4-hydroxybenzyl)cyclopentanone (3ALP).

Human papillomavirus (HPV) has been directly related to acuminate warts and cervical cancer, the second most common neoplasia among women. Given the lack of treatment against the virus itself, many medications have been utilised, mainly aiming in modifying the host’s immunological response. We present the case of a 54 years old postmenopausal patient with a history of vaginal cuff wart and HPV persistence that we managed in our clinic for 6 months with a mix of curcumin, aloe vera, amla and other natural ingredients. As the patient was found to be intolerant to imiquimod (one of the most common conservative methods of treatment) we attempted the use of curcumin, which was applied to the area of the wart three times per week for 6 months. Both clinical and colposcopical improvement was noted in regular clinic visits with regression of the lesion. The outcome of this case encourages our view that curcumin should be considered as a significant treatment modality against HPV infection and acuminate warts.

Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaherpesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that we provide interventions to keep them at bay, especially in immunocompromised patients. While numerous experimental vaccines are under consideration, current intervention consists solely of antiviral chemotherapeutic agents. This review explores all of the clinically approved drugs used to prevent the worst sequelae of recurrent outbreaks by these viruses.

Background. Higher fatty alcohols are a valuable raw material for pharmacology and can serve as an adaptogen in crop production, reducing post-stress effects in the cultivation of crops. Policosanols are linear saturated aliphatic alcohols with carbon atoms ranging from 20–24 to 32–34. Cereal germ contains some of the policosanols and can serve as a potential source for the isolation, purification, and further use of this class of chemical compounds. The purpose of the research is to study the features of the higher fatty alcohols content in various anatomical organs of barley seedlings under the influence of an ultra-high frequency electromagnetic field. Materials and methods. The content of some higher fatty alcohols in barley seedlings after grain processing by ultrahigh frequency electromagnetic fields was determined by the method of chromatography-mass spectrometry. Results. The character of distribution of 4 fatty alcohols – tetraconanol (lignocerin alcohol), docosanol (begenyl alcohol), dodecanol (lauric alcohol) and hexadecanol (cetyl alcohol) – in the anatomical organs of barley seedlings is shown. In sprouts, roots, shells and endosperm higher fatty alcohols are distributed unevenly. The predominant aliphatic alcohol is tetracosanol, found in all the studied anatomical parts of the seedling is dodecanol. Treatment of barley seeds before germination in the electromagnetic field of ultrahigh frequency allowed to increase the content of almost all studied alcohols. Conclusions. After microwave treatment, the number of detectable aliphatic alcohols increased by 1,67 times relative to the control. The higher fatty alcohols are unevenly distributed over the organs of the barley seedling – the maximum is noted in the sprouts, the minimum – in the endosperm. Barley sprouts can be considered as a potential source of lignocerine and begenyl alcohols, where their content ishigh and is 26,20 and 5,67 %, respectively. The content of tetracosanolcan be increased more than twice by pre-microwave treatment of barley grain.

Antimicrobial resistance is a major public health concern in infection control. Hence, a multi-pronged approach is necessary to curb the severity of infections. The present study entails the identification of docosanol (fatty alcohol) from Streptomyces as a novel antibiofilm agent which can target the virulence factors of MRSA. Results showed that docosanol as a potent antibiofilm agent and found to inhibit several virulence factors of MRSA. The antibiofilm efficacy of docosanol analyzed through light and scanning electron microscopy showed a significant reduction in adherent cells. Moreover, analysis of three-dimensional structure of biofilm matrix by confocal laser scanning microscope demonstrated effective antibiofilm potential of docosanol. In addition, docosanol reduced the survival rate of MRSA in healthy human blood and enhanced the neutrophil-mediated killing by interfering with hemolysin production. RT-qPCR analysis revealed the down regulation of several virulence genes, possibly by affecting the expression of the accessory gene regulator (agr) system and transcriptional regulator sarA. These findings suggest that docosanol could effectively reduce the biofilm phenotype and virulence production, and thus becomes a promising candidate to treat MRSA infections.

This 22-year-old woman is referred to you by her physician for evaluation and management of the findings noted on her lips. The patient reports that around 4 months ago, she developed a “cold sore” on the lower lip likely due to prolonged sun exposure during a sailing trip. Her initial attempts to address this with over-the-counter docosanol cream were unsuccessful. She consulted with her physician who prescribed penciclovir cream. The lesions were unresponsive after two courses of penciclovir and continued to progress in severity and extent (they involved the whole lower lip and upper lip vermilion). She was prescribed valacyclovir PO and has been on this medication for the past 3 months.

The major challenges to the clinical application of zidovudine are its moderate aqueous solubility, relative short half-life, and incapability to go across BBB after systemic administration makes the brain one of the dominant HIV reservoirs. We investigated the development of zidovudine-loaded NLCs based on docosanol and oleic acid which were further surface modified with PEG4000 and HAS. The drug content and entrapment efficiencies were assessed by UV analysis. The mean diameter of the SyLN was found to be at 54.7 ± 1.4 nm with a zeta potential of −21.6 ± 0.2 mV and relatively low polydispersity. The NLCs showed excellent stability in the refrigerated condition, in blood serum and were safe for IV administration. In vitro release studies showed a sustained release profile of zidovudine in aCSF. In vivo plasma and brain pharmacokinetics investigation in a rat model showed that SyLN and SyLN-Peg NLCs rapidly reached the brain and yielded higher MRT, Cmax, and AUC. The rat brain pharmacokinetic data confirm the brain localization and accumulation of the developed NLCs delivering AZT in a sustained manner for a prolonged period of time, which is further confirmed by CLSM images of brain cryosections labeled with SyLN-C6 NLCs. Our results suggest that the developed docosanol NLCs could be a promising drug delivery system for long-term brain delivery of zidovudine in the treatment of Neuro-AIDS.

Watercress oil (WCO) is the seed oil of Nasturtium officinale, Brassicaceae family. WCO is a cosmetic for hair growth approved by the Saudi Food and Drug Authority (SFDA). The study aimed to analyze by GC–MS, the phytochemical profile and the safety of WCO as a cosmetic according to SFDA, validates the traditional method of applying hot oil mixtures to the scalp, and also reports the pH, UV absorption, and in-silico binding mechanism of fatty acids for hair growth. The absorption of UV-B light (284.50 nm and 290.60 nm) by WCO suggests that it acts as a sunscreen for the scalp. The pH of the marketed WCO, 5.53 ± 0.02, shall not damage the scalp and hair. The GC–MS analysis confirmed fatty acids as the principal constituents (65.65%) of WCO composed of monounsaturated fatty acids (MUFAs): cis-11-Octadecenoic acid (17.14%), cis-9-Octadecenoic acid (17.11%), cis-13-Eicosenoic acid (11.13%), cis-11-Eicosenoic acid (3.48%), and cis-13-Docosenoic acid (1.64%); saturated fatty acid: n-Hexadecanoic acid (12.89%); saturated fatty alcohol: Docosanol (2.26%). The GC–MS results also confirmed the absence of colorants, toxic solvents, and therapeutic substances in WCO, a cosmetic requirement, according to SFDA. The densities of mixtures of WCO + Coconut oil was 0.801 ± 0.03 mg/mL, and WCO + Olive oil was 0.885 ± 0.01 mg/mL; the kinematic viscosities of WCO + Coconut oil was 21.5 ± 0.0 mm2/s, and WCO + Olive oil was 28.6 ± 0.1 mm2/s at 40℃, which was lesser than the mixtures at 27℃. The decrease in density and viscosity of hot oil mixtures can improve the penetration of oil into the hair filament, which substantiated the traditional application method. In-silico, molecular docking results revealed that all the fatty acid constituents except Docosanol contributed to the hair growth promotion effect by activating MAPK1, MAPK3, and MAPKp38 receptors. This work is the first report on WCO to establish the phytochemical profile to confirm SFDA standard by GC–MS and its in-silico efficiency of activation of MAPK receptors for hair growth.

Painful oral vesiculoerosive diseases (OVD) include lichen planus, pemphigus vulgaris, mucous membrane pemphigoid, erythema multiforme, and recurrent aphthous stomatitis. OVD lesions have an immunopathic cause. Treatment is aimed at reducing the immunologic and the following inflammatory response. The mainstay of OVD management is topical or systemic corticosteroids to include topical triamcinolone, fluocinonide, and clobetasol, whereas systemic medications used in practice can include dexamethasone, prednisone, and prednisolone. Oral herpetic lesions can be primary or recurrent. If management is desired, they can be treated by topical or systemic antiviral drugs. Topical antiviral creams include prescription acyclovir, penciclovir and over-the-counter docosanol.

Article history:Received 21 January 2015Accepted 2 May 2015Available online 28 May 2015Keywords:CHO-K1 cellsGrowth-arrestedHuman melanoma cellsPolycosanols Background:Polycosanolsderivedfromplantspecieshavetraditionallybeenusedinmedicineasantiproliferativeagentsfortreatingvariousviruses(primarilytheherpessimplexvirus).However,fewstudieshavestudiedtheireffects on hyperproliferative cell lines. In this work, the antiproliferative capacity of polycosanols from tall-oilpitch, obtained from black liquor soaps in the kraft pulping process of cellulose (specifically from Pinus radiata,Pinus taede,andEucalyptus globulus), was evaluated on CHO-K1 and CRL-1974 human melanoma cell lines.Results: The proliferative capacities and cell viabilities were measured for 72 and 140 h, respectively. TreatmentwithdocosanolproduceddifferentialeffectsontheCHO-K1andhumanmelanomacellsandsignificantlyaffectedtheir proliferation rates, but not their cell viabilities. Tetracosanol produced a significant negative effect on theproliferation of human melanoma cells, and this effect was less than that caused by docosanol. However, it hadno effect on the proliferation of CHO-K1 cells and did not induce any significant effect on the viability of thestudied cell lines.Conclusion: Docosanol and tetracosanol induced antiproliferative effects on the studied cell lines and exhibitedsignificantly greater effects on the oncogenic cell lines. Prior to this study, the capacity of these polycosanolshas never been investigated. Future studies will be necessary to determine their mechanisms of action onthese cell systems.©2015Pontificia UniversidadCatolicadeValparaiso. Production and hosting byElsevierB.V. Allrights reserved.

Despite their importance as bioactive compounds and authentication parameters in olive oil, the response of policosanol aliphatic alcohols to even the most influential sources of variability is practically unknown. To investigate policosanol variation in olive oil as a result of variety, ripening, and oil storage temperature, 36 samples were subjected to gas chromatographic (GC-FID) and mass spectrometric (GC-MS) analysis, and results were processed by univariate (ANOVA) and multivariate (SLDA) statistics. The concentration (mg/100 g) and relative amount (%) of pentacosanol accounted for the most variation due to variety. The largest influence of ripening was observed for pentacosanol (%) and docosanol (%). Docosanol, tricosanol, and tetracosanol amounts mostly increased during ripening, whereas those of pentacosanol, hexacosanol, heptacosanol, and octacosanol decreased in Črna and Rosinjola oils, whereas Buža showed different patterns in some cases. Variations as a result of storage were lower and inconsistent. Results suggest that the investigated olive oils retained the bulk of their health beneficial features of policosanol origin throughout shelf-life. Relatively successful differentiation of oils achieved by multivariate models pointed to the potential use of policosanol alcohols as chemical indicators of varietal origin which are independent on ripening degree, and vice versa, applicable both for fresh and stored oils.

Soxhlet-petroleum ether extraction was used to obtain oil from tomato seeds. Three tomato cultivars from South Italy (Principe Borghese, Rebelion F1 and San Marzano) were studied. Policosanol is a mixture of long chain linear fatty alcohols (n-alkanols), its content and composition was found to be highly significantly influenced by cultivar. Seven fatty alcohols were detected: docosanol (C22-ol), tricosanol (C23-ol), tetracosanol (C24-ol), pentacosanol (C25-ol), hexacosanol (C26-ol), heptacosanol (C27-ol) and octacosanol (C28-ol). The highest policosanol content was found in Principe Borghese 71.88 mg/Kg. Octacosanol was the linear alcohol present in highest quantity, i.e. 38-42% of the total linear alcohols detected in tomato seed oils (TSO). Chemometrics was applied to study the differences among cultivars. The sum of even long chained fatty alcohols was always more than 95% of the total policosanol content. One-way ANOVA and principal component analysis well differentiated the three cultivars.

Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyces cerevisiae platform strain for high-level production of very-long-chain fatty acid (VLCFA)-derived chemicals. Through rewiring the native fatty acid elongation system and implementing a heterologous Mycobacteria FAS I system, we establish an increased biosynthesis of VLCFAs in S. cerevisiae. VLCFAs can be selectively modified towards the fatty alcohol docosanol (C22H46O) by expressing a specific fatty acid reductase. Expression of this enzyme is shown to impair cell growth due to consumption of VLCFA-CoAs. We therefore implement a dynamic control strategy for separating cell growth from docosanol production. We successfully establish high-level and selective docosanol production of 83.5 mg l−1 in yeast. This approach will provide a universal strategy towards the production of similar high value chemicals in a more scalable, stable and sustainable manner., Production of chemicals by microbial fermentation is an economical alternative to chemical synthesis. Here the authors re-engineer the yeast S. cerevisiae to produce the very long chain fatty alcohol docosanol by expressing a heterologous Mycobacteria fatty acid synthase and a specific fatty acid reductase.

Evening primrose (Oenothera biennis L., Onagraceae) is a wild medicinal plant of Central American origin that is now one of the most widely used herbal medicines in different parts of the world. Oil extracted from it seeds is traditionally used in the treatment of eczema, asthma, rheumatoid arthritis, breast problem, premenstrual and menopausal syndrome, all they have an inflammatory component. The present study demonstrates the in vitro anti-inflammatory effect of long-chain fatty alcohols, minor compounds isolated from Evening primrose oil (EPO).A mixture of long chain fatty alcohols (LCFAs) was isolated from the non-triacylglycerol fraction of the EPO. Hexacosanol (C26OH: 38.65%), tetracosanol (C24OH: 31.59%), docosanol (C22OH: 11.36%) and octocosanol (C28OH: 7.64%), were the major constituents, identified and quantified by GC and GC-MS. LCFA was tested with LPS stimulated murine peritoneal macrophage. This fraction, significantly and dose-dependently decreased nitric oxide production induced by LPS (P0.001) and the inhibitory effect seems to be consequence of an action at the level of the inducible nitric-oxide synthethase (iNOS) gene enzyme expression rather than to a direct inhibitory action on enzyme activity. The release of PLA2 and TXB2 also was significantly inhibited by LCFAs (P0.001) although LCFAs did not affect to PGE2 generation, however the western blot assay showed that LCFAs reduced cyclooxygenase-2 enzyme gene expression at all doses assayed. In the same way, the secretion of inflammatory cytokines interleukin 1β (IL-1β) and tumour necrosis factor α (TNF-α) from LPS-stimulated murine macrophage, were also significantly reduced (P0.001).These results demonstrates the anti-inflammatory activity of LCFAs, providing an additional value about the role of bioactive minor compounds in the beneficial effect of EPO and supports its traditional uses in inflammatory processes management.

In the present study pufferfish, Arothron immaculatus muscle methanol extract (AIME) was used to evaluate the antidiabetic activity against the high-fat diet (HFD) in streptozotocin (STZ) induced diabetic rat models. Initially, the In vitro antioxidant activity of the different muscle extract was evaluated which showed that AIME has higher efficiency to scavenge the free radicals. The animal study results revealed that the AIME could decrease the blood glucose level after 14 days of oral treatment and recover the animal from the severe progression of the disease. The LC-ESI/MS analysis of AIME extract revealed the presence of compounds such as docosahexaenoic acid, adrenic acid, docosanol, codeine and metoprolol. Among these compounds, docosahexaenoic acid, adrenic acid and docosanol are reported for its antidiabetic studies. Hence, the muscle is recommended to consume by humans as natural food in order to overcome the development of diabetes. This is the first study on the muscle extract of marine pufferfish which is used as antidiabetic agent to treat the diabetes-induced in the animal model.