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  1. Fulltext Hydroxytyrosol Promotes Proliferation of Human Schwann Cells: An In Vitro Study
    Kamil K, Yazid MD, Idrus RBH, Kumar J
    Int J Environ Res Public Health, 2020 06 19;17(12).
    PMID: 32575426 DOI: 10.3390/ijerph17124404
    Recent advances in phytomedicine have explored some potential candidates for nerve regeneration, including hydroxytyrosol (HT). This study was undertaken to explore the potential effects of HT on human Schwann cells' proliferation. Methods: The primary human Schwann cell (hSC) was characterized, and the proliferation rate of hSC supplemented with various concentrations of HT was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and protein expression of glial fibrillary acidic protein (GFAP) and p75 nerve growth factor receptor (p75 NGFR) were evaluated via the immunofluorescence technique. Results: In vitro culture of hSCs revealed spindle-like, bipolar morphology with the expression of specific markers of hSC. Hydroxytyrosol at 10 and 20 ng/mL significantly increased the proliferation of hSCs by 30.12 ± 5.9% and 47.8 ± 6.7% compared to control (p < 0.05). Cell cycle analysis showed that HT-treated hSCs have a higher proliferation index (16.2 ± 0.2%) than the control (12.4 ± 0.4%) (p < 0.01). In addition, HT significantly increased the protein expression of GFAP and p75NGFR (p < 0.05). Conclusion: HT stimulates the proliferation of hSCs in vitro, indicated by a significant increase in the hSC proliferation index and protein expression of hSCs' proliferation markers, namely p75 NGFR and GFAP.
    Matched MeSH terms: Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/pharmacology
  2. Fulltext Antifilarial activity of caffeic acid phenethyl ester on Brugia pahangi in vitro and in vivo
    Al-Abd NM, Nor ZM, Junaid QO, Mansor M, Hasan MS, Kassim M
    Pathog Glob Health, 2017 Oct;111(7):388-394.
    PMID: 29065795 DOI: 10.1080/20477724.2017.1380946
    Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5, 10, 15, 20 μg/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial activity of CAPE was measured in worms by quantification of Wolbachial wsp gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both in vitro and in vivo. 20 μg/ml of CAPE halts the release of mf in vitro by day 6 of post treatment. Also, the number of adult worms recovered in vivo were reduced significantly during and after treatment with 50 mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/therapeutic use
  3. Fulltext Fibrinolytic activity and dose-dependent effect of incubating human blood clots in caffeic acid phenethyl ester: in vitro assays
    Elnager A, Hassan R, Idris Z, Mustafa Z, Wan-Arfah N, Sulaiman SA, et al.
    Biomed Res Int, 2015;2015:627471.
    PMID: 25664321 DOI: 10.1155/2015/627471
    Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.
    Matched MeSH terms: Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/pharmacology
  4. Caffeic acid phenethyl ester (CAPE) reverses fibrosis caused by chronic colon inflammation in murine model of colitis
    Tambuwala MM, Kesharwani P, Shukla R, Thompson PD, McCarron PA
    Pathol Res Pract, 2018 Nov;214(11):1909-1911.
    PMID: 30170869 DOI: 10.1016/j.prp.2018.08.020
    Fibrosis is known to be the hallmarks of chronic inflammation of the bowel. Epithelial damage due to inflammation compromises the barrier function of the gastrointestinal tract. This barrier dysfunction leads to further spread of inflammation resulting in a chronic state of inflammation. This chronic inflammation leads to development of fibrosis, which has very limited therapeutic options and usually requires surgical removal of the affected tissue. Our previous work has shown that Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, has been found to be protective in experimental colitis via enhancement of epithelial barrier function. However, the impact of CAPE on resolution of fibrosis in the long-term is unknown. The aim of this follow up study was to investigate the effect of CAPE on colon fibrosis in a chronic model of Dextran sulphate sodium induced colitis in mice. Dextran sulphate sodium (DSS) 2.5% w/v was administered in drinking water to induce colitis in C57/BL6 mice for 5 days on the 6th day DSS was stopped and test group mice were treated with intraperitoneal administration of CAPE (30 mg kg-1 day-1) for a further 7 days. Disease activity index (DAI) score, colon length and tissue histology and level of tissue fibrosis was observed. CAPE-treated mice had significantly lower levels of DAI, tissue inflammation scores and fibrosis as compared with control group. Our results show that CAPE is effective in resolving colon fibrosis in chronic inflammation. Thus, we can conclude CAPE could be a potential therapeutic agent for further clinical investigations for treatment of fibrosis in inflammatory bowel diseases in humans.
    Matched MeSH terms: Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/pharmacology
  5. Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles
    Siddique MI, Katas H, Amin MCIM, Ng SF, Zulfakar MH, Buang F, et al.
    J Pharm Sci, 2015 Dec;104(12):4276-4286.
    PMID: 26447747 DOI: 10.1002/jps.24666
    Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.
    Matched MeSH terms: Phenylethyl Alcohol/adverse effects; Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/chemistry
  6. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model
    Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Buang F, Sahudin S
    Int J Pharm, 2013 Feb 28;444(1-2):109-19.
    PMID: 23337632 DOI: 10.1016/j.ijpharm.2013.01.024
    In this study, hydroxytyrosol (HT; a potent antioxidant) was co-administered with hydrocortisone (HC) to mitigate the systemic adverse effects of the latter and to provide additional anti-inflammatory and antioxidant benefits in the treatment of atopic dermatitis (AD). The co-loaded nanoparticles (NPs) prepared had shown different particle sizes, zeta potentials, loading efficiencies, and morphology, when the pH of the chitosan solution was increased from 3.0 to 7.0. Ex vivo permeation data showed that the co-loaded NPs formulation significantly reduced the corresponding flux (17.04μg/cm(2)/h) and permeation coefficient (3.4×10(-3)cm/h) of HC across full-thickness NC/Nga mouse skin. In addition, the NPs formulation showed higher epidermal (1560±31μg/g of skin) and dermal (880±28μg/g of skin) accumulation of HC than did a commercial HC formulation. Moreover, an in vivo study using an NC/Nga mouse model revealed that compared to the other treatment groups, the group treated with the NPs formulation efficiently controlled transepidermal water loss (13±2g/m(2)/h), intensity of erythema (207±12), and dermatitis index (mild). In conclusion, NPs co-loaded with HC/HT is proposed as a promising system for the percutaneous co-delivery of anti-inflammatory and antioxidative agents in the treatment of AD.
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/chemistry
  7. An in vitro study of the antifungal activity of Trichoderma virens 7b and a profile of its non-polar antifungal components released against Ganoderma boninense
    Angel LP, Yusof MT, Ismail IS, Ping BT, Mohamed Azni IN, Kamarudin NH, et al.
    J Microbiol, 2016 Nov;54(11):732-744.
    PMID: 27796927
    Ganoderma boninense is the causal agent of a devastating disease affecting oil palm in Southeast Asian countries. Basal stem rot (BSR) disease slowly rots the base of palms, which radically reduces productive lifespan of this lucrative crop. Previous reports have indicated the successful use of Trichoderma as biological control agent (BCA) against G. boninense and isolate T. virens 7b was selected based on its initial screening. This study attempts to decipher the mechanisms responsible for the inhibition of G. boninense by identifying and characterizing the chemical compounds as well as the physical mechanisms by T. virens 7b. Hexane extract of the isolate gave 62.60% ± 6.41 inhibition against G. boninense and observation under scanning electron microscope (SEM) detected severe mycelial deformation of the pathogen at the region of inhibition. Similar mycelia deformation of G. boninense was observed with a fungicide treatment, Benlate(®) indicating comparable fungicidal effect by T. virens 7b. Fraction 4 and 5 of hexane active fractions through preparative thin layer chromatography (P-TLC) was identified giving the best inhibition of the pathogen. These fractions comprised of ketones, alcohols, aldehydes, lactones, sesquiterpenes, monoterpenes, sulphides, and free fatty acids profiled through gas chromatography mass spectrometry detector (GC/MSD). A novel antifungal compound discovery of phenylethyl alcohol (PEA) by T. virens 7b is reported through this study. T. virens 7b also proved to be an active siderophore producer through chrome azurol S (CAS) agar assay. The study demonstrated the possible mechanisms involved and responsible in the successful inhibition of G. boninense.
    Matched MeSH terms: Phenylethyl Alcohol/isolation & purification; Phenylethyl Alcohol/pharmacology; Phenylethyl Alcohol/chemistry
  8. Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in sepsis models
    Kassim M, Mansor M, Kamalden TA, Shariffuddin II, Hasan MS, Ong G, et al.
    Shock, 2014 Aug;42(2):154-60.
    PMID: 24667629 DOI: 10.1097/SHK.0000000000000179
    Excessive free radical production by immune cells has been linked to cell death and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death that has been identified in several pathological conditions. Caffeic acid phenethyl ester (CAPE) is an active component of honeybee products and exhibits antioxidant, anti-inflammatory, and immunomodulatory activities. The present study examined the ability of CAPE to scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with lipopolysaccharide/interferon-γ that was used as an in vitro model. Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia and cecal ligation and puncture) were used as in vivo models. The level of serum 3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results demonstrated that CAPE significantly improved the viability of lipopolysaccharide/interferon-γ-treated RAW 264.7 cells and significantly inhibited nitric oxide production, with effects similar to those observed with an inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE exclusively inhibited the synthesis of peroxynitrite from the artificial substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus, CAPE attenuates the inflammatory responses that lead to cell damage and, potentially, cell death through suppression of the production of cytotoxic molecules such as nitric oxide and peroxynitrite. These observations provide evidence of the therapeutic potential of CAPE treatment for a wide range of inflammatory disorders.
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/pharmacology; Phenylethyl Alcohol/therapeutic use
  9. Transdermal anti-inflammatory activity of bilayer film containing olive compound hydroxytyrosol: physical assessment, in vivo dermal safety and efficacy study in Freund's adjuvant-induced arthritic rat model
    Ng SF, Tan LS, Buang F
    Drug Dev Ind Pharm, 2017 Jan;43(1):108-119.
    PMID: 27588411 DOI: 10.1080/03639045.2016.1224893
    Previous studies have shown that hydroxytyrosol (HT) can be a potential alternative therapeutic agent for the treatment of rheumatoid arthritis (RA). However, HT is extensively metabolized following oral administration, which leads to formulating HT in a topical vehicle to prolong drug action as well as to provide a localized effect. Hidrox-6 is a freeze-dried powder derived from fresh olives and contains a high amount of HT (∼3%) and other polyphenols. Alginate bilayer films containing 5% and 10% Hidrox-6 were formulated. The films were characterized with respect to their physical, morphology, rheological properties; drug content uniformity; and in vitro drug release. Acute dermal irritancy tests and a skin sensitization study were carried out in rats. An efficacy study of the bilayer films for RA was conducted using Freund's adjuvant-induced polyarthritis rats. Animal data showed that the bilayer film formulations did not cause skin irritancy. The efficacy in vivo results showed that the Hidrox-6 bilayer films lowered the arthritic scores, paw and ankle circumference, serum IL-6 level and cumulative histological scores compared with those measured for controls. The topical Hidrox-6 bilayer films improve synovitis and inflammatory symptoms in RA and can be a potential alternative to oral RA therapy.
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives*; Phenylethyl Alcohol/metabolism; Phenylethyl Alcohol/chemistry
  10. Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects
    Siddique MI, Katas H, Jamil A, Mohd Amin MCI, Ng SF, Zulfakar MH, et al.
    Drug Deliv Transl Res, 2019 04;9(2):469-481.
    PMID: 29159691 DOI: 10.1007/s13346-017-0439-7
    Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives*
  11. Fulltext Characterization of the key aroma compounds in three types of bagels by means of the sensomics approach
    Lasekan O, Dabaj F, Muniandy M, Juhari NH, Lasekan A
    BMC Chem, 2021 Mar 13;15(1):16.
    PMID: 33714268 DOI: 10.1186/s13065-021-00743-4
    BACKGROUND: To evaluate the impact of cold fermentation time on bagel rolls, the key aroma-active compounds in the volatile fractions obtained from three different bagel rolls through solvent assisted flavor evaporation (SAFE) were sequentially characterized by an aroma extract dilution analysis (AEDA), quantified by stable isotope dilution and analyzed by odor activity values (OAVs) respectively.

    RESULTS: Findings revealed 40 aroma-active compounds with flavor dilution (FD) factor ranges of 2-1024. Of these, 22 compounds (FD ≥ 16) were quantified by stable isotope dilution assays (SIDA). Subsequent analysis of the 22 compounds by odor activity values (OAVs) revealed 14 compounds with OAVs ≥ 1 and the highest concentrations were obtained for 2,3-butanedione, 2-phenylethanol, 3-methylbutanal and acetoin respectively. Two recombination models of the bagels (i.e. 24 h and 48 h bagels) showed similarity to the corresponding bagels. Omission tests confirmed that 2,3-butanedione (buttery), acetoin (buttery), 2-acetyl-1-pyrroline (roasty), 5-methyl-2-furanmethanol (bread-like), (Z)-4-heptenal (biscuit-like) and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, were the key aroma compounds. Additionally, acetic acid, butanoic acid, 2-phenylethanol (honey-like), 3-methylbutanoic acid, 2/3-methylbutanal, vanillin, 3-methylbutanol, methional were also important odorants of the bagel.

    CONCLUSION: Whilst the long, cold fermented bagels exhibited roasty, malty, buttery, baked potato-like, smoky and biscuit-like notes, the control bagels produced similar but less intense odor notes.

    Matched MeSH terms: Phenylethyl Alcohol
  12. Chemical components of marine sponge derived fungus fusarium proliferatum collected from Pulau Tinggi, Malaysia
    Mosadeghzad Z, Zuriati Zakaria, Asmat A, Gires U, Wickneswari R, Pittayakhajonwut P, et al.
    Sains Malaysiana, 2012;41:333-337.
    Marine fungus Fusarium proliferatum derived from marine sponge collected along Pulau Tinggi, Malaysia was cultivated on Potato Dextrose Broth and incubated for 7 days at 30oC. The liquid cultures were then extracted using ethyl acetate. The crude extract was investigated for its anti-microbial activity and was passed through Sephadex column and the fractions were collected. Reverse phase HPLC was used to monitor the component of crude extract. HPLC guided purification of crude extract resulted in the isolation of linoleic acid, 4-hydroxy phenethyl alcohol, 2,5-furandimethanol and adenosine. Their structures were elucidated by spectroscopic methods.
    Matched MeSH terms: Phenylethyl Alcohol
  13. Fulltext Efficient immuno-modulation of TH1/TH2 biomarkers in 2,4-dinitrofluorobenzene-induced atopic dermatitis: nanocarrier-mediated transcutaneous co-delivery of anti-inflammatory and antioxidant drugs
    Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E
    PLoS One, 2014;9(11):e113143.
    PMID: 25396426 DOI: 10.1371/journal.pone.0113143
    The present study was conducted with the aim to investigate the immuno-modulatory and histological stabilization effects of nanocarrier-based transcutaneous co-delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation, the clinical and pharmacological efficacies of nanoparticle (NP)-based formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual examination of AD induction in experimental mice indicated remarkable control of NP-based formulations in reducing pathological severity of AD-like skin lesions. Therapeutic effectiveness of NP-based formulations was also evaluated by comparing skin thickness of AD-induced NP-treated mice (456±27 µm) with that of atopic mice (916±37 µm). Analysis of the immuno-spectrum of AD also revealed the dominance of NP-based formulations in restraining immunoglobulin-E (IgE), histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-α (VEGF-α), and T-helper cells (TH1/TH2) producing cytokines in serum and skin biopsies of tested mice. These anti-AD data were further supported by histological findings that revealed alleviated pathological features, including collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC and HT can be considered as a promising therapy for managing immunological and histological spectra associated with AD.
    Matched MeSH terms: Phenylethyl Alcohol/administration & dosage; Phenylethyl Alcohol/analogs & derivatives
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