Pharmacognostıcal Research On Developıng Plant-Based Cosmetıc Products

Kozmesötik ürünler etkili madde olarak sentetik, hayvansal ve bitkisel kaynaklı ürünleri içermektedir. Ancak son yıllarda bitkisel ekstrelerin kozmetik formülasyonlarda kullanımı; özellikle sentetik maddelerin yan etkileri nedeniyle oldukça artmıştır. Bağ dokusu elemanlarından oluşan ve cildin orta tabakası olan dermis, derinin esneklik ve direncini sağlar. Bağ dokusunun ana bileşenlerinden iki önemli protein olan elastin ve kolajen, cildin direnci ve elastikiyetinden sorumludur ve serbest oksijen radikallerinin tetiklediği elastaz ve kolajenaz enzimleri ile parçalanmaları cilt yaşlanmasına eşlik eden kırışıklıklara neden olur. Serbest oksijen radikalleri kararlı olmayıp, pek çok fizyolojik hasara neden olmakta, birçok hastalığın yanısıra, çeşitli dokularda hücre hasarı ile de ilişkilendirilmektedir. Antioksidan maddeler, çeşitli sebepler sonucunda vücutta üretilen zararlı serbest radikalleri süpüren maddelerdir. Tirozinaz ise mikroorganizma, bitki ve hayvanlarda yaygın olarak bulunan ve bakır içeren melanojenik bir enzimdir. Son zamanlarda hiperpigmentasyon tedavisinde, cilt beyazlatma ve leke giderme amacıyla güvenli ve etkili tirozinaz inhibitörleri arayışı önem kazanmıştır. Bu bilgiler doğrultusunda, tez kapsamında yaklaşık 100 adet bitkisel ekstrenin ve propolisin elastaz, kollajenaz ve tirozinaz enzim inhibitör etkileri, ELISA mikrotiter plak yöntemi ile geniş çaplı bir tarama uygulanarak incelenmiş ve antioksidan etkileri de bir dizi in vitro yöntemle tespit edilmiştir. Taramada kullanılan enzimlere karşı aktif ekstrelere biyoaktivite-yönlendirmeli fraksiyonlama işlemi uygulanmış ve aktiviteden sorumlu olması muhtemel madde(ler)in izolasyonu ve yapı tayinleri gerçekleştirilmiştir. Etkili ekstrelerden 2 tanesinden hareketle mikroemülsiyon, 2 tanesi ile de krem şeklinde kozmetik formülasyonlar geliştirilmiş, marka ismi yaratılmış ve prototip ürünler hazırlanmıştır.Cosmeceuticals contain synthetic, plant-, and animal-derived materials. However, use of herbal ingredients in cosmetic formulations are on increase mostly due to side effects of synthetic compounds. Dermis, which is the middle layer of the skin consisting of connective tissue components, provides flexibility and resistance to skin. Elastin and collagen, two important proteins being the main components of the connective tissue, are responsible for resistance and elasticity of the skin. Hydrolysis of them through elastase and collagenase triggered by free oxygen radicals cause wrinkle formation accompanied by skin aging. Reactive oxygen species are not stable and cause a huge level of physiological damage, while they are associated with cell damage in various tissues in addition to many diseases. Antioxidant compounds are the substances that may scavenge harmfull free radicals produced in the body by different reasons. Tyrosinase is a copper-containing melanogenic enzyme that is present in microorganisms, plant, and animal tissues. Recently, search on reliable and potent tyrosinase inhibitors have gained importance for skin-bleaching purpose in hyperpigmentation therapy. In the light of this information, approximately 100 herbal extracts and propolis were investiagted for their elastase, collagenase, and tyrosinase inhibitory effects using ELISA microtiter assays in a large screening in the thesis, while their antioxidant effect was determined using various in vitro methods. The active extracts against the enzymes used in the screening were subjected to bioactivity-guided fractination and the isolation and structural characterization of the active compound(s) were realized. The cosmetic formulations, 2 in microemulsion and 2 in cream form from the effective extracts, were developed, a brand name was created, and the prototype products were prepared

P491, I Trionfi / Petrarca. Image 078

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Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads

Seventeen natural coumarin derivatives; badrakemin (1), 14′-acetoxybadrakemin (2), badrakemone (3), 14′-acetoxybadrakemone (4), colladonin (5), colladonin acetate (6), 14′-acetoxycolladonin (7), karatavicinol (8), deltoin (9), smyrnioridin (10), marmesin (11), osthol (12), oxypeucedanin (13), oxypeucedanin hydrate (14), isoimperatorin (15), scopoletin (16), and umbelliprenin (17), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer's disease as well as tyrosinase (TYR) as the target for Parkinson's disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates

Butyrylcholinesterase-inhibiting natural coumarin molecules as potential leads

Seventeen natural coumarin derivatives; badrakemin (1), 14′-acetoxybadrakemin (2), badrakemone (3), 14′-acetoxybadrakemone (4), colladonin (5), colladonin acetate (6), 14′-acetoxycolladonin (7), karatavicinol (8), deltoin (9), smyrnioridin (10), marmesin (11), osthol (12), oxypeucedanin (13), oxypeucedanin hydrate (14), isoimperatorin (15), scopoletin (16), and umbelliprenin (17), were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the sister enzymes that play a critical role in the pathology of Alzheimer’s disease as well as tyrosinase (TYR) as the target for Parkinson’s disease. The tested coumarins were more selective against BChE, where the coumarins 2, 5, 8, and 15 (IC50 = 30.3 μM, 29.2 μM, 37.2 μM, and 50.1 μM, respectively) displayed higher BChE inhibition than the reference (galanthamine, IC50 = 60.2 μM) at 100 μg/mL. Only four coumarins (2, 5, 9, and 15) showed inhibition against AChE. Binding conformations of the coumarins (2, 5, 8, 9, and 15) within the active sites of AChE and BChE were explored via molecular docking experiments. The docked compounds were oriented by the interactions with the oxyanion hole and the peripheral anionic site residues of AChE/BChE. The coumarin derivatives 1–17 was found to have no or low inhibition (2.03 ± 0.92 %–12.91 ± 0.40 %) against TYR at 100 μg/mL. Our findings revealed that coumarins could be promising lead compounds for designing novel anti-Alzheimer drug candidates

Evaluation of Activity of Some 2,5-Disubstituted Benzoxazole Derivatives against Acetylcholinesterase, Butyrylcholinesterase and Tyrosinase: ADME Prediction, DFT and Comparative Molecular Docking Studies

In this study, p-tert-butyl at position 2 and acetamide bridged 4-substituted piperazine/piperidine at position 5 bearing benzoxazole derivatives were evaluated for their in vitro inhibitory activity against AChE, BChE and Tyrosinase, which are important targets in reducing the adverse effects of Alzheimer's disease. The most active 1 g inhibited the BChE at a concentration of 50 mu M by 54 +/- 0.75%. Molecular docking studies of the compounds against BChE (PDB: 4BDS) were performed with Schrodinger and AutoDock Vina and the results were compared. Schrodinger docking scores were found to be more consistent. Estimated ADME profiles and bioactivity scores of the compounds were calculated and found to be compatible with Lipinski and other limiting rules. Geometric optimization parameters, MEP analysis and HUMO and LUMO quantum parameters of the most active 1 g were calculated by using DFT/B3LYP theory and 6-311 G (d,p) base set and results was viewed

Survey of 55 Turkish Salvia taxa for their acetylcholinesterase inhibitory and antioxidant activities

In the current work, our target was to screen inhibitory potentials of 55 Turkish Salvia taxa, 28 of which are endemic, against acetylcholinesterase (AChE), which is a chief enzyme in pathogenesis of Alzheimer's disease (AD). The dichloromethane, ethyl acetate, and methanol extracts prepared from 55 Salvia taxa were tested for their AChE inhibitory activity at 25, 50, and 100 mu g/ml using an ELISA microplate reader. The extracts were also screened for their scavenging effect against DPPH radical and iron-chelating capacity. Total phenol and total flavonoid contents of Salvia fruticosa were determined. Among the 165 Salvia extracts screened, only the dichloromethane extract of S. fruticosa showed inhibition towards AChE at 100 mu g/ml having 51.07% of inhibition, while only the dichloromethane and ethyl acetate extracts of Salvia cilicica had a notable iron-chelating capacity at 100 mu g/ml having 54.71% of chelating capacity. Most of the extracts showed remarkable scavenging effect against DPPH radical

Biological evaluation and docking studies of some benzoxazole derivatives as inhibitors of acetylcholinesterase and butyrylcholinesterase

A series of 2,5-disubstituted-benzoxazole derivatives (1-13) were evaluated as possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results demonstrated that the compounds exhibited a broad spectrum of AChE and BChE inhibitory activity ranging between 6.80% and 90.21% except one compound which showed no activity against AChE at the specified molar concentration. Another derivative displayed a similar activity to that of reference drug (galanthamine) for inhibition of AChE and BChE. In addition, molecular docking of the compounds into active site of AChE was performed using recombinant human AChE (PDB ID: 4ey6) in order to understand ligand-protein interactions

A mechanistic investigation on anticholinesterase and antioxidant effects of rose (Rosa damascena Mill.)

In the current study, neuroprotective effect of the essential oil and aromatic waters of rose was investigated by in vitro and in silico methods. The samples were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Since oxidative damage is associated with neurodegeneration, antioxidant activity of the samples was determined by DPPH radical scavenging, metal-chelation, and ferric-reducing antioxidant power (FRAP) assays. Their chemical composition was elucidated by GC-MS. Anti-cholinesterase effects of the main components (citronellol, geraniol, nerol, and phenylethyl alcohol) were also examined. The rose oil showed a noteworthy inhibition against AChE (60.86 +/- 1.99%) and BChE (51.08 +/- 1.70%) at 1000 mu g/mL and low activity in DPPH radical scavenging and FRAP tests. Phenylethyl alcohol exerted higher cholinesterase inhibition than other components and applied further to molecular docking simulations. Docking and binding energies supporting experimental results show that the compound is more selective towards BChE than AChE. (C) 2013 Elsevier Ltd. All rights reserved

Evaluation of Cholinesterase Inhibitory and Antioxidant Activities of Wild and Cultivated Samples of Sage (Salvia fruticosa) by Activity-Guided Fractionation

In European folk medicine, Salvia species have traditionally been used to enhance memory. In our previous study of 55 Salvia taxa, we explored significant anticholinesterase activity of cultivated S. fruticosa. In this study, we compared the inhibitory activity of dichloromethane, ethyl acetate, and ethanol extracts of 3 wild-grown samples and 1 cultivated sample of S. fruticosa against acetylcholinesterase and butyrylcholinesterase enzymes (which are associated with pathogenesis of Alzheimer's disease) by using the spectrophotometric Ellman method. Antioxidant activities were assessed by determining 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, iron-chelating capacity, and ferric-reducing antioxidant power. The dichloromethane extract of the cultivated sample was then subjected to fractionation by using open column chromatography and medium-pressure liquid chromatography to obtain the most active fraction by activity-guided fractionation. All fractions and subfractions were tested in the same manner, and inactive subfractions were discarded. The essential oil of the cultivated sample was analyzed by gas chromatography-mass spectrometry