New insights into plant volatiles and es

() 1 New Insights into Plant Volatiles and Essential Oils K Hüs ü Ca BAŞER1,2,3,4* & Fatih DEMIRCI2,3 1Bahçeşehir U iversity, Te h ology Tra sfer Offi e, Beşiktaş, Ista ul, Turkey 2Bade io Biote h olo[.]

New Insights into Plant Volatiles and Essential Oils K Hüs ỹ Ca BAER1,2,3,4* & Fatih DEMIRCI2,3 Bahỗeehir U iversity, Te h ology Tra sfer Offi e, Beşiktaş, Ista ul, Turkey Bade io Biote h ology Ltd, Eskişehir, Turkey Anadolu University, Faculty of Phar a y, Depart e t of Phar a og osy, Eskişehir, Turkey King Saud University, Faculty of Science, Department of Botany and Microbiology, Riyadh, Saudi Arabia www.khcbaser.com , www.badebio.com Abstract Plant volatiles and essential oils comprise thousands of secondary metabolites in a wealth of biochemical, biological and pharmacological diversity Throughout our research over three decades we have employed many innovative techniques such as pilot scale distillation to molecular distillation, microdistillation, absorptive and headspace etc techniques for the isolation; and several chromatospectral techniques for the chemical characterization Beside semisyntheses, we have employed biotransformation techniques to modify the chemical composition of essential oils and volatiles for further investigations and applications Biological and pharmacological evalutions of the essential oils, volatiles and their derivatives were in a broad spectrum both in vitro and in vivo Antioxidant, antimicrobial, antimalarial, antiprotozoal, cytotoxicity, genotoxicity assays; anticancer assays including cancer cell lines, apoptotic and (anti)angiogenic activities; antiinflammatory, choleretic, hepatoprotective, analgesic, woundhealing activities, etc However, in recent years we use the combination of essential oil components such as the nature does for the enhancement or decrease of the biological/pharmacological activity Due to their highly volatile nature and solubility problems it is difficult to work with essential oils and volatiles, however, current research suggest that the bright future potential on this topic is still promising for diverse interdisciplinary collaborative work Plan of presentation - Flora of Turkey - Our research group - Infrastructure, Capabilities and Research Staff - Essential oil and volatiles isolation - - Headspace (HS) Techniques - - Static and Dynamic HS Trapping - - SPME HS - - Microdistillation - - Molecular distillation - - Microwave distillation - - Spinning band fractional distillation system - - SFE - Chromatospectral Techniques for authentication and analysis - - Preparative GC - - Multidimensional GC/MS (Enantiomeric separations) - - GC/MS, GC/FT-IR, GC-AED - - HPTLC – prepTLC - Applications - - Microbial transformations - - Antimicrobial activity testing - - Bioactivities: Antioxidant, antimicrobial, antimalarial, antiprotozoal, cytotoxicity, genotoxicity assays; anticancer assays including cancer cell lines, apoptotic, angiogenic and antiangiogenic activities; antiinflammatory, choleretic, hepatoprotective, analgesic, woundhealing activities, etc - Commercialization of research activities Flora of Turkey Turkey is situated at the junction of two continents and has land in Asia and Europe between 42oN and 36oN latitudes Its land mass is about 0.8 million square kilometer supporting a population of 75 million Turkey has a transect between the sea level and Mount Ararat (5137 m) It is under the influence of three different climates: Mediterranean, Continental and Oceanic, and is at the junction of three important phytogeographic regions: IranoTuranian, Euro-Siberian and Mediterranean This is the reason why the flora of Turkey is rich and diverse It comprises 12.068 flowering plant taxa belonging to 10.279 species This is ca 2000 less than the number of flowering plant species growing in Europe 1/3 of the flora comprises aromatic plants and >33% of the flora consists of endemic species 1000 plant taxa are used in folk medicine variously Flora of Turkey is well documented in the Flora of Turkey and the East Aegean Islands, edited by the late Prof Dr P H Davis and published by Edinburgh University Press in 10 volumes (9+1 supplement) between 1965-1988 Vol 11, the second supplement, edited by Prof Dr Tu a Eki , Prof Dr Adil Gü er, Prof Dr Neri a Özhatay a d Prof Dr K Hüs ü Ca Başer was published in 2000 by the same publisher Our Research Group Our research group has been screening especially the aromatic the flora of Turkey in the last 33 years systematically for their essential oil yield and compositions as well as their biological activities 33 genera out of 46 in the family Lamiaceae have been investigated by our group The other important families investigated are Apiaceae and Asteraceae, etc Pharmacognosy Department at the Faculty of Phar a y of A adolu U i ersity i Eskişehir, Turkey was founded in 1968 Pharmacognosy facilities were strengthened in 1980s with the advent of TBAM ( Medicinal and Aromatic Plant and Drug Research Centre) and with its staff strength of 25 pharmacists, chemists, biologists and chemical engineers under the direction of Prof Dr K Hüs ü Ca Başer The group published its first research paper in 1982 (1) and made 11 publications until 1991 The first paper on essential oils appeared in 1991 (2) and since then >1000 research papers have been published by our group, over 90% of them being on essential oils Research interests of the department include botany and ethnobotany, chemistry, analysis, biological activity and pharmacology, enzyme inhibitory activities, technology; biotransformations, biopolymerizations etc of essential oils and volatile compounds; phytochemical and biological screening programmes on the analysis f the aromatic plants of Turkey; collaborative work with Europe, USA, South Africa, Uzbekistan, Kazakhstan, Japan, Pakistan, India, Mongolia, Brunei We have contributed chapters on essential oils in the following important books: Analysis and Quality Assessment of Essential Oils, K.H.C Baser, In: K Tuley De Silva (Ed.) A Manual on the Essential Oil Industry, UNIDO, Vienna , pp 155-177 (1995) Chemistry of Essential Oils, K.H.C Baser and F Demirci In: Flavours and Fragrances: Chemistry, Bioprocessing and Sustainability, R.G Berger (Ed.), Springer, Berlin, pp 43-86 (2007) Handbook of Essential Oils: Science, Technology and Applications, K.H.C Baser and G Buchbauer (Eds.), CRC Press, Boca Raton, London, New York (2010) Essential Oils, K Husnu Can Baser and F Demirci, Kirk-Othmer Encyclopedia of Chemical Technology, 4th Edition, Wiley, 1–37 (2011) Analysis of Essential Oils and Fragrances by Gas Chromatography, K.H.C Baser and T Ozek, In: Gas Chromatography, Ed C Poole, Elsevier, Oxford, pp 519-527 (2012) The department is well equipped with basic infrastructure and laboratories as well as sophisticated chromatospectral instrumentation such as Gas Chromatography/Mass Spectrometry (GC/MS) systems, Multidimensional GC/MS system, Preparative GC, Liquid Chromatography/Mass Spectrometry (LC/MSMS) system, fully fledged High Performance Thin Layer Chromatography (HPTLC) system, High Pressure Liquid Chromatography (HPLC) systems, Medium Pressure Liquid Chromatography (MPLC) system, Flash Chromatography and has access to 500 MHz NMR, GC-FTIR, GC-AED (Atomic Emission Detector), TLC scanner, Chromatotron and pilot plants and semi-industrial plants for large scale extraction and distillation, chemical reactor The laboratories possess all necessary facilities for essential oil research and development such as numerous sets of small and medium scale Clevenger apparata, Likens-Nickerson Simultaneous Distillation-Extraction (SDE) apparata, microdistillation, microwave distillation, Short Path Distillation (Molecular Distillation) systems, dynamic headspace trapping set up, Headspace Solid Phase Microextraction (HS-SPME) set up, Supercritical Fluid Extraction (SFE) system, Extraction with Fluidized Gasses (Phytosol) equipment, Spinning Band Fractional Distillation system, etc Applications Due to the paucity of time, I shall not elaborate on the phytochemical research carried out by our group, but focus mainly on the more recent innovative activities concerning microbial transformations and biological activity studies References given in this text are restricted to our papers published in the last years Microbial Transformations (Biotransformations) In 1929, Bio J.B.S Haldane stated that microorganisms can be your friend if you know how to o u i ate ith the sayi g Why trou le to ake o pou ds yourself he a ug ill it for you? Biotransformation is the use of microorganisms or enzymes as biocatalysts to produce novel or known metabolites from particular substrates When a substrate is added to a microbial medium, the microorganism metabolizes the substrate by first making it more soluble in its body fluid During this stage, functional groups are added to the molecule Such compounds are extracted from the medium before they are completely metabolized Biotransformations are useful techniques employed in biotechnology, nanotechnology and green chemistry One of the major advantages of biotransformation is the production of natural metabolites from natural starting materials, generally resulting in more or less bioactive compounds from micro to ton scale Biotransformation processes are generally considered as environmental friendly due to mild conditions in aqueous medium where fermention conditions are relatively simple and safe resulting in highly regio- and/or stereoselective one pot reactions in a relatively short time ranging from hours to weeks Such reactions generally mimic in vivo biosyntheses of compounds, therefore, are useful in elucidating biosynthetic pathways under in vitro conditions Biotransformations are considered low energy consuming, hence more economical compared to conventional chemical syntheses Our research group possesses more than 150 microorganisms for use in microbial transformations as well as antimicrobial screening tests We, either use volatile compounds isolated from essential oils or essential oils as such for microbial transformations Example of some substrated studies include terpenes such as p-cymene, terpinolene, a-pinene, bpinene, carvone enantiomers, carvacrol and thymol and their methyl ethers, and several sesquiterpenes The metabolites are either extracted from the medium by immiscible solvent extraction or by headspace solid phase microextraction (HS-SPME) Analyses are mainly performed by Thin Layer Chromatography (TLC) and GC/MS Some of our results are summarized in the following figures and some representative publications are listed in the references (3-10) Bioassays In vitro and in vivo microtechniques Antimicrobial (Agar diffusion, microdilution, TLC-bioautography) - Antibacterial (MRSA, Serratia, E coli, H pylori ) - Antifungal (human and plant pathogens) - Anticandidal Antioxidant - 96 well format – spectrophotometrically - TLC bioautography Enzyme inhibition assays (UV spectrophotometry – 96 well format, TLC bioautography) - Acetylcholine esterase (AchE) - Butyrylcholine esterase (BuChE) - Lipoxygenase (LOX) - Cycloxygenase (COX) - Neuraminidase (NEUR) - -Glycosidase (-Gly) - Lipase Bioluminex – Vibrio fischeri toxicity assay (TLC-bioautography) Chorioallantoic membrane assay (CAM) – Angiogenic/antiangiogenic activity Antimicrobial assays Due to the fact that pathogenic microorganisms are gaining resistance to antibiotics, research into discovering new antimicrobial agents is a hot area Discovering new microbiostatic and microbicidal agents has been our aim in performing antimicrobial assays We use various in vitro techniques such as agar diffusion, microdilusion and TLCbioautographic methods against Gram + and Gram - bacteria such as E coli, MRSA (Methicillin-resistant Staphylococcus aureus), Serratia, Helicobacter pylori, etc., human and plant pathogenic fungi (Aspergillus, Penicillium, Fusarium, Cladosporium, etc.), yeasts such as Candida spp Some representative publications can be found in references 11-47 Antioxidant assays Oxidation reactions are vital for biological systems However, oxidations may also cause damage to their normal functioning through oxidative stress caused by free radicals such as ROS (reactive oxygen species) Antioxidants inhibit the oxidation of molecules at cellular level They are also used for preservation of foods, cosmetics, and other products prone to oxidation Essential oils and their components are valuable and promising sources of natural antioxidants We test antioxidant activity by the following assays: Total phenol content, total flavonoid content, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH●) scavenging activity, TLC bioautography, iron(III) to iron (II) reduction, determination of inhibition of linoleic acid peroxidation, determination of inhibition of -carotene/linoleic acid co-oxidation, ABTS radical scavenging activity, estimation of Trolox Equivalent Antioxidant Capacity (TEAC) using ABTS radical, online HPLC-ABTS● and HPLC-DPPH ●screening tests A list of our representative publications are given in references 48-56 Enzyme inhibitory activity assays Enzymatic reactions play a major role in many pathogeneses Therefore, inhibition of responsible enzymes for pathogenies is important to stop progression of a disease Many drugs are enzyme inhibitors Therefore, finding new enzyme inhibitors for various diseases is a promising and rewarding research area We perform the following enzyme inhibitory assays: Acetylcholine esterase (AchE) and Butyrylcholine esterase (BuChE) assays for the discovery of anti-Alzheimer agents and insecticides Lipoxigenase (LOX) and Cycloxygenase (COX) inhibitory activities are for antiinflammatory agents Neuraminidase (NEUR) inhibition is for the treatment of viral diseases such as influenza -Glycosidase and Lipase inhibitions are important for diabetes and obesity type metabolic disorders Related references are 57-65 Vibrio fisheri toxicity assay is for the in vitro determination of acute and chronic toxicity It is a practical, fast and sensitive assay suitable for microdilution and TLC-bioautography of indvidual compounds and mixtures Vibrio fischeri is a luminescent Gram (-) marine bacterium The Latin name of this organism has recently been changed to Aliivibrio fischeri This bacterium emits luminescence while alive When it is exposed to toxic chemicals it loses its luminesces and dies Bioluminex method measures the acute and chronic LD50 values of the tested samples Related references 14, 15, 25, 26, 28 Chorioallantoic membrane assay (CAM) Angiogenesis and anti-angiogenesis have been associated with tumour pathogenesis CAM of the chick embryo serves as an excellent vascularization (angiogenesis) environment The test is conducted on fertilized chicken eggs at early embryo stage Test sample is introduced onto the chorioallantoic membrane in pellet form for 24 hours Stereomicroscopic examination allows to distinguish membrane toxicity, angiogenic effect, antiangiogenic effect as well as antiinflammatory effect In anti-angiogenic effect, capillaries around the pellet diminish, however, in angiogenesis development of new capillaries are evident and measurable Using an inflammatory agent like SDS (Sodium dodecylsulfate) causes membrane irritation seen as extrene vascularization in a star like form An antiinflammatory agent reverses this effect Related references are 66-72 Insecticidal and antiparasitic activities Mosquito repellent, biting deterrence, larvicidal, acaricidal, anti-tick and insecticidal assays are conducted in collaboration with Mississippi University (OleMiss), Oxford, MS (USA) Antiprotozoal and antileishmanial actvities were also conducted in collaboration with UK and Pakistani collaborators (73-80) Pharmacological and clinical studies The only clinical study we have conducted is on oregano water which is the hydrosol of Origanum onites oil distillation The study was conducted on 48 patients having mild hyperlipidaemia 32 of the patients were in the study group Patients in the study group were given 25 ml of the hydrosol daily for three months Beneficial effects of the hydrosol on lipid profiles, antioxidant status, endothelial functions of mild hyperlipidaemic functions (81) Pharmacological studies conducted include hepatoprotective and ischemia reperfusion defects inhibition of carvacrol in liver, antiinflammatory, antinociceptive, anticolitis, anticonvulsant, anticancer activities of essential oils and natural aromachemicals (82-86) Commercialization of Research Activities Research for the sake of research is good for the generation new knowledge However, if it only helps publication of new articles, innovation is buried in libraries Therefore, it is the duty of a responsible researcher to find ways of application of research results This is best achieved by collaboration with commercial companies interested in research and development, or by establishing a new company by the researcher himself There are ample opportunities for innovative researchers nowadays in many countries including Turkey, Europe and the world In Turkey, university researchers can set up their spin off companies in technoparks with high incentives We have taken up this opportunity to set up our company BadeBio Biotechnology Ltd (www.badebio.com) at Anadolu University Technopark in Eskisehir, Turkey in order to implement our research ideas on commercial level We have our own laboratories and have access to all the research facilities of the university at a nominal fee We are currently implementing R&D projects for a major American flavours and fragrances supplier company, and for other foreign and Turkish companies for the development of novel products We have conducted R&D projects and taken part in European project consortia as a microSME We have organized 28th and 42nd International Symposium on Essential Oils (ISEO) in 1997 and 2011 respectively in Eskişehir a d Antalya, Turkey and International PSE Symposium on Terpenes in 2010 in Istanbul 45th ISEO (www.iseo2014.org) is organized by us on 7-10 September 2014 in Istanbul, Turkey REFERENCES 1) H.Guinaudeau, A.J.Freyer, R.D.Minard, M.Shamma, K.H.C.Baser, Structural Variations Among the Aporphine-Benzylisoquinoline Dimers,Tetrahedron Letters, 23(25) 2523-2526 (1982) 2) K.H.C.Baser, E Sezik, G Tumen, Composition of the Essential Oil of Ziziphora clinopodioides Lam., J Essent Oil Res., 3(4) 237-239 (1991) 3) Kira , Ö Özşe , T Çelik, “ İlha , B Ye i e Gürsu, F Demirci, Microbial Transformations of Isophorone by Alternaria alternata and Neurospora crassa, Nat Prod Comm (1) 59-61, 2013 4) G Iscan, N Kirimer, F Demirci, B.Demirci , Y Noma, K.H.C Baser, Biotransformation of (R)-(-)alpha-phellandrene: Antimicrobial activity of its major metabolite, Chemistry and Biodiversity, 9, 1525-1532, 2012 5) İ Kira , Z Dur eyla , N Kiri er, K H.C Başer, Y No a, F De ir i, Biotra sfor atio of α-Cedrol and Caryophyllene Oxide by the Fungus Neurospora crassa, Nat Prod Commun (4) 515-518, 2010 6) F Demirci, T Akar, TA Demir, I Kiran, N Kirimer, K.H.C Baser, Hydroxylation of selected sesquiterpenes by the fungus Neurospora crassa, Planta Medica, 72, 981, 2006 7) F Demirci, N Kirimer, Y Noma, K.H.C Baser, Biotransformation of (-)-Carvone, Z Naturforsch C 59 389-392, 2004 8) A Farooq, M.I Choudhary, Atta-ur-Rahman, S Tahara, K.H.C Baser, F Demirci, Detoxification of Terpinolene by Plant Pathogenic Fungus Botrytis cinerea, Z Naturforsch C 57 (9/10), 863-866, 2002 9) A Farooq, S.Tahara, M I Choudhary, A Rahman, K H C Baser, F Demirci, The Microbiological Oxidation of (-)-alpha-Pinene by Botrytis cinerea, Z Naturforsch C 57 (7/8), 686-690, 2002 10) F Demirci, N Kirimer, B Demirci, Y Noma, K H C Baser, Screening of Biotransformation Products of Carvone Enantiomers by Headspace-SPME/GC-MS, Z Naturforsch C 56 (1/2), 58-64, 2001 11) S Celen, A.D Azaz, M Kurkcuoglu, K.H.C Baser, Chemical Composition of Endemic Thymus spathulifolius Hausskn and Velen Essential Oil and its Antimicrobial and Antioxidant Activity from Turkey, J Essent Oil Bear Plants (JEOBP) 15(4) 628-636 (2012) 12) G Iscan, B Demirci, F Demirci, F Goger, N Kirimer, Y.B Kose, K.H.C Baser, Antimicrobial and Antioxidant Activities of Stachys lavandulifolia subsp lavandulifolia Essential Oil and its Infusion, Nat Prod Commun 7(9) 1241-1244 (2012) 13) G Iscan, N Kirimer, F Demirci , B.Demirci , Y Noma and K.H.C Baser, Biotransformation of ( R )(-)-alpha-phellandrene: Antimicrobial activity of its major metabolite, Chemistry and Biodiversity, 9, 1525-1532 (2012) 14) K Polatoglu, F Demirci, B Demirci, N Goren, K.H.C Baser, Essential Oil Composition and Antimicrobial Activities of Tanacetum chiliophyllum (Fisch & Mey.) Schultz Bip var monocephalum Grierson from Turkey, Rec Nat Prod 6(2) 184-188 (2012) 15) K Polatoglu, F Demirci, B Demirci, K.H.C Baser, N Goren, Biological activity and the essential composition of Tanacetum chiliophyllum var chiliophyllum chemotypes from Turkey, Ind Crops Prods., 39, 97-105 (2012) 16) B Kunduhoglu, M Kurkcuoglu, M E Duru, K.H.C Baser, Antimicrobial and anticholinesterase activities of the essential oils isolated from Salvia dicroantha Stapf., Salvia verticillata L subsp.amasiaca (Freyn and Bornm.) Bornm and Salvia wiedemannii Boiss., J Med Plants Res 5(29) 6484-6490 (2011) 17) G Iscan, Y B Kose, B Demirci, K.H.C Baser, The Anticandidal Essential Oil of Nepeta transcaucasica Grossh., Chemistry and Biodiversity,8, 2144-2148 (2011) 18) N Tabanca, B Demirci, I Gurbuz, F Demirci, J.J Becnel, D.E Wedge, K.H.C Baser, Essential Oil Composition of Five collections of Achillea biebersteinii from Central Turkey and Their Antifungal and Insecticidal Activity, Nat Prod Commun 6(5) 701-706 (2011) 19) A Abdel-Megeed, A.N Al-Rahma, A.A Mostafa, K.H.C Baser, Biochemical characterization of antimicrobial activity of glycolipids produced by Rhodococcus erythropolis, Pakistan J Bot., 43(2) 1323-1334 (2011) 20) M Kurkcuoglu, G Iscan, F Demirci, H Malyer, E Erdogan, K.H.C Baser, Composition and Antibacterial Activity of The Essential Oil of Ferulago confusa Velen, J Essent Oil Res., 22(6) 490-492 (2010) 21) T Ozek, N Tabanca, F Demirci, D E Wedge, K.H.C Baser, Enantiomeric distribution of some linalool containing essential oils and their biological activities, Rec Nat Prod., 4(4) 180-192 (2010) 22) N Bilge Oral, L Vatansever, B Duman Aydin, C Sezer, A Guven, M Gulmez, K.H.C Baser, M Kurkcuoglu, Effect of Oregano Essential Oil on Biofilms Formed by Staphylococi and Escherichia coli, Kafkas Universitesi Veteriner Fakultesi Dergisi, 16 (Suppl A), 23-29 (2010) 23) N Tabanca, U.R Bernier, M Tsikola, J.J.Becnel, B Sampson, C Werle, B Demirci, K.H.C Baser, E.K Blythe, C Pounders, D.E Wedge, Eupatorium capillifolium Essential Oil: Chemical Composition, Antifungal Activity, and Insecticidal Activity, Nat Prod Commun 5(9) 1409-1416 (2010) 24) T Serbetci, B Demirci, C Bozkurt Guzel, S Kultur, M Ergü e , K.H.C Baser, Essential Oil Composition, Antimicrobial and Cytotoxic Activities of Two Endemic Stachys cretica Subspecies (Lamiaceae) from Turkey, Nat Prod Commun 5(9) 1369-1374 (2010) 25) K Polatoglu, F Demirci, B Demirci, N Goren, K.H.C Baser, Essential oil composition and antibacterial activity of Tanacetum argenteum (Lam.) Willd ssp argenteum and T densum (Lab.) Schultz Bip ssp amani Heywood from Turkey, J Oleo Sci 59 (7) 361-367 (2010) 10 26) K Polatoglu, F Demirci, B Demirci, N Goren, K.H.C Baser, Antimicrobial activity and essential oil composition of a new Tanacetum argyrophyllum (C Koch) Tvzel var argyrophyllum chemotyp,e J Oleo Sci., 59(6) 307-313 (2010) 27) M Akin, B Demirci, Y Bagci, K.H.C Baser, Antibacterial activity and composition of the essential oils of two endemic Salvia sp from Turkey, African J Biotechnol., 9(15) 2322-2327 (2010) 28) K Polatoglu, F Demirci, B Demirci, N Goren, K.H.C Baser, Antibacterial activity and the variation of Tanacetum parthenium (L.) Schultz Bip essential oils from Turkey, J Oleo Sci., 59 (4) 177-184 (2010) 29) S Alan, B Demirci, G Iscan, Y.B Kose, K.H.C Baser, Composition and anticandidal activity of the essential oil of Hypericum perforatum L., Asian J Chem., 22 (2) 1315-1320 (2010) 30) T Askun, K H C Baser, G.Tumen, M Kurkcuoglu, Characterization of Essential Oils of Some Salvia Species and Their Antimycobacterial Activities, Turkish J Biol., 34, 89-95 (2010) 31) N Kavalcioglu, L Acik, F Demirci, B Demirci, H Demir, K.H.C Baser, Biological activities of Bellis perennis volatiles and extracts, Nat Prod Commun 5(1) 147-150 (2010) 32) A Kurtulmus, T Fafal, T Mert, H Saglam, B Kivcak, T Ozturk, B Demirci, K H C Baser, Chemical composition and antimicrobial activity of the essential oils of three Anthemis species from Turkey, Chem Nat Comp 45 (6) 900-904 (2009) 33) K.H.C Baser, M.Kurkcuoglu, T Askun, G.Tumen, Anti-tuberculosis Activity of Daucus littoralis Sibth et Sm (Apiaceae) From Turkey , J Essent Oil Res., 21, 572-575 (2009) 34) H Kirmizibekmez , B Demirci , E Yesilada, K H C Baser, F Demirci, Chemical Composition and Antimicrobial Activity of the Essential Oils of Lavandula stoechas L ssp stoechas Growing Wild in Turkey, Nat Prod Commun., 4(7) 1001-1006 (2009) 35) F Demirci, B Demirci, I Gurbuz, E Yesilada, K.H.C Baser, Characterization and Biological Activity of Achillea teretifolia Willd and A nobilis L subsp neilreichii (Kerner) Formanek Essential Oils, Turkish J Biol., 33,129-136 (2009) 36) B Demirci, M Toyota, F.Demirci, M Y Dadandi, K.H.C Baser, Anticandidal pimaradiene diterpene from Phlomis essential oils, Comptes Rendus Chimie, 12, 612-621 (2009) 37) E.M Suleimenov, T Ozek, F Demirci, B Demirci, K.H.C Baser, S.M Adekenov, Component composition of essential oils of Artemisia lercheana and A sieversiana of the flora of Kazakhstan Antimicrobial activity of A sieversiana essential oil, Chem Nat Comp., 45(1) 120-123 (2009) 38) D.E Wedge, J.A Klun, N Tabanca, B Demirci, T Ozek, K.H.C Baser, Z Liu, S Zhang, C.L Cantrell, J Zhang, Bioactivity-guided Fractionation and GC-MS Fingerprinting of Angelica sinensis and A archangelica Root Components for Antifungal and Mosquito Deterrent Activity, J Agric Food Chem., 57, 464-470 (2009) 39) D.E Wedge, N Tabanca, B J Sampson, C Werle, B Demirci, K.H.C Baser, P Nan, J Duan, Z Liu, Antifungal and insecticidal activity of two Juniperus essential oils, Nat Prod Com., 4(1) 123-127 (2009) 40) A.M.Gencler Ozkan, B Demirci, F Demirci, K.H.C Baser, Composition and Antimicrobial Activity of Essential Oil of Ferulago longistylis Boiss Fruits, J Essent Oil Res., 20, 569-573 (2008) 11 41) N Tabanca, D.E Wedge, X Wang, B Demirci, K.H.C Baser, L Zhou, S.J Cutler, Chemical Composition and Antifungal Activity of Angelica sinensisEssential Oil against three Colletotrichum species, Nat Prod Commun., (7) 1073-1078 (2008) 42) E.M Suleymenov, T Ozek, F Demirci, B Demirci, K.H.C Baser, S.M Adekenov, The composition and antimicrobial activity of Artemisia kasakorum essential oil, Khim Prir Soedin., 207-208 (2008); Chem Nat Comp., 44(2) 263-265 (2008) 43) S.M El-Massarany, F.A Abbas, B Demirci, K.H.C Baser, S.I Khan, A.J Al-Rehaily, J.S Mossa, E.A Abourashed, Chemical Composition and Biological Activity of the Essential Oil ofCommiphora opobalsamum L., Journal of Herbs, Spices and Medicinal Plants, 13(4) 111-122 (2007) 44) F Demirci, K Guven, B Demirci, M.Y Dadandi, K.H.C Baser, Antibacterial activity of two Phlomis essential oils against food pathogens, Food Control, 19, 1159-1164 (2008) 45) N Kirimer, B Demirci, G Iscan, K H C Baser, H Duman, Composition of the essential oils of two Sideritis species from Turkey and antimicrobial activity, Chem Nat Comp., 44(1) 121-123 (2008) 46) Composition and Antimicrobial Activity of the Oils of Ferula szowitsianaDC from Turkey, G Ozek, T Ozek, G Iscan, K.H.C Baser, A Duran, E Hamzaoglu, J Essent Oil Res., 20, 186-190 (2008) 47) M Kosar, B Demirci, F Demirci, K.H.C Baser, The effect of maturation on the composition and biological activity of the essential oil of a commercially important Satureja species from Turkey:Satureja cuneifolia Ten., J Agric Food Chem., 56, 2260-2265 (2008) 48) T Serbetci, N Ozsoy, B Demirci, A Can, S Kultur, K.H.C Baser, Chemical composition of the essential oil and antioxidant activity of methanolic extracts from fruits and flowers of Hypericum lydium Boiss., Industrial Crops and Products, 36, 599-606 (2012) 49) M Kosar, H.J Damien-Dorman, K.H.C Baser, R Hiltunen, Salvia officinalis L.: Composition and antioxidant -related activities of a crude extract and selected sub-fractions, , Nat Prod Commun 5(9) 1453-1456 (2010) 50) I Orhan, B Demirci, I Omar, H Siddiqui, E Kaya, M I Choudhary, G Ecevit-Genc, N Ozhatay, B Sener, K.H.C Baser, Essential oil compositions and antioxidant properties of the roots of twelve Anatolian Paeonia taxa with special reference to chromosome counts, Pharm Biol 48(1) 10-16 (2010) 51) N Kavalcioglu, L Acik, F Demirci, B Demirci, H Demir, K.H.C Baser, Biological activities of Bellis perennis volatiles and extracts, Nat Prod Commun 5(1) 147-150 (2010) 52) F Demirci, B Demirci, I Gurbuz, E Yesilada, K.H.C Baser, Characterization and Biological Activity of Achillea teretifolia Willd and A nobilis L subsp neilreichii (Kerner) Formanek Essential Oils, Turkish J Biol., 33,129-136 (2009) 53) H.J D Dorman, M Kosar, K.H.C Baser, R Hiltunen, Phenolic profile and antioxidant evaluation of Mentha x piperita(Peppermint) extracts, Nat Prod Com., 4, 1-8 (2009) 54) S.M El-Massarany, F.A Abbas, B Demirci, K.H.C Baser, S.I Khan, A.J Al-Rehaily, J.S Mossa, E.A Abourashed, Chemical Composition and Biological Activity of the Essential Oil of Commiphora opobalsamum L., Journal of Herbs, Spices and Medicinal Plants, 13(4) 111-122 (2007) 55) M Kosar, F Goger, K.H.C Baser, In Vitro Antioxidant Properties and Phenolic Composition of Salvia virgataJacq from Turkey, J Agric Food Chem., 56, 2369-2374 (2008) 12 56) M Kosar, B Demirci, F Demirci, K.H.C Baser, The effect of maturation on the composition and biological activity of the essential oil of a commercially important Satureja species from Turkey: Satureja cuneifolia Ten., J Agric Food Chem., 56, 2260-2265 (2008) 57) B.Demirci, H.E Temel, T Portakal, H Kır ızı ek ez, F De ir i, K.H.C Baser, Inhibitory effect of Calamintha nepeta subsp glandulosa essential oil on lipoxygenase, Turk J Biochem., 36(4) ; 188–192 (2011) 58) F.S Senol, I Erdogan Orhan, M Kurkcuoglu, M.T.H Khan, A Altintas, B Sener, K.H.C Baser, A mechanistic investigation on anticholinesterase and antioxidant effects of rose (Rosa damascena Mill.), Food Res Int 53, 502-509 (2013) 59) I Erdogan Orhan, F.S.Senol, B Demirci, N Ozturk, K.H.C Baser, B Sener, Phytochemical characterization of Phagnalon graecum Boiss by HPLC and GC-MS with its enzyme inhibitory and antioxidant activity profiling by spectrophotometric methods, Food Analytical Methods, 6, 1-9 (2013) 60) O.Ustun, F.S.Senol, M Kurkcuoglu, I Erdogan Orhan, M Kartal, K.H.C Baser, Investigation on chemical composition, anticholinesterase and antioxidant activities of extracts and essential oil of Turkish Pinus species and pycnogenol, Industrial Crops and Products, 38, 115 - 123 (2012) 61) B Kunduhoglu, M Kurkcuoglu, M E Duru, K.H.C Baser, Antimicrobial and anticholinesterase activities of the essential oils isolated from Salvia dicroantha Stapf., Salvia verticillata L subsp.amasiaca (Freyn and Bornm.) Bornm and Salvia wiedemannii Boiss., J Med Plants Res 5(29) 6484-6490 (2011) 62) N Tabanca, U.R Bernier, M Tsikola, J.J.Becnel, B Sampson, C Werle, B Demirci, K.H.C Baser, E.K Blythe, C Pounders, D.E Wedge, Eupatorium capillifolium Essential Oil: Chemical Composition, Antifungal Activity, and Insecticidal Activity, , Nat Prod Commun 5(9) 1409-1416 (2010) 63) D.E Wedge, J.A Klun, N Tabanca, B Demirci, T Ozek, K.H.C Baser, Z Liu, S Zhang, C.L Cantrell, J Zhang, Bioactivity-guided Fractionation and GC-MS Fingerprinting of Angelica sinensis and A archangelica Root Components for Antifungal and Mosquito Deterrent Activity J Agric Food Chem., 57, 464-470 (2009) 64) G Ma, H Tabanca, K.H.C Baser, N Kirimer, D Pasco, I Khan, S Khan, Inhibition of NF-kBmediated Transcription and Induction of Apoptosis in Human Breast Cancer Cells By Epoxypseudoisoeugenol-2-methyl butyrate, Cancer Chemotherapy and Pharmacology, 63(4) 673-680 (2009) 65) I Orhan, S Aslan, M Kartal, B Sener, K.H.C Baser, Inhibitory effect of Turkish Rosmarinus officinalis L on acetylcholinesterase and butyrylcholinesterase enzymes, Food Chem., 108(2) 663-668 (2008) 66) Kıya H.T., De ir i B., Başer K.H.C., De ir i F., The in vivo evaluation of anti-angiogenic effects of Hypericum essential oils using the chorioallantoic membrane assay, Pharmaceutical Biology 52 (1) 4450, 2014 67) Bostancioglu R.B., Kurkcuoglu M., Baser K.H.C., Koparal A.T., Assessment of anti-angiogenic and anti-tumoral potentials of Origanum onites L essential oil, Food Chem Toxicol 50(6) 2002-2008, 2012 68) Demirci, F., Duymus, H., Kiyan H.T., Demirci B., Baser K.H.C., The in vivo angiogenic evaluation of betulin, Planta Med 76(12) 1349, 2010 13 69) Demirci B., Kiyan H.T., Baser K.H.C., Demirci F.,The in vivo angiogenic evaluation of Thymbra spicata L essential oil, Pharmacognosy Magazine, 6(22) S127, 2010 70) Demirci B, Demirci F., Dö ez, A.A., Fra z, G., Paper, D.H Baser K.H.C Chemical and Biological Investigations of Salvia Essential Oils, Pharmaceutical Biol., 43, 666 2005 71) Demirci F, Paper DH, Franz G, Başer K.H.C I estigatio of the Origanum onites L essential oil using the chorioallantoic membrane (CAM) assay J Agric Food Chem., 52(2):25 2004 72) Demirci B, Dadandi MY, Paper DH, Fra z G, Başer K.H.C Che i al o positio of the esse tial oil of Phlomis linearis Boiss & Bal., and biological effects on the CAM-assay: a safety evaluation Z Naturforsch C.; 58(11-12): 826 2003 73) A Ali, B Demirci, H.T Kiyan, U.R Bernier, M Tsikolia, D.E Wedge, I.A Khan, K.H.C Baser, N Tabanca, Biting Deterrence and Larvicidal Activity of Ruta chalepensis L Essential Oil and its Major Individual Constituents against Mosquitoes, J Medical Entomology 50(6) 1267-1274 (2013) 74) B Demirci, M Tsikolia, U.R Bernier, N.M Agremonte, S.I Alqasoumi, M.A Al-Yahya, A.J AlRehaily, H.S Yusufoglu, F Demirci, K.H.C Baser, I.A Khan, N Tabanca, Phoenix dactylifera L spathe essential oil: Chemical composition and repellent activity against the yellow fever mosquito, Acta Tropica 128, 557-560 (2013) 75) A Ali, C.C Murphy, B Demirci, D.E Wedge, B.J Sampson, I.A Khan, K.H.C Baser, N Tabanca, Insecticidal and biting deterrent activity of rose-scented Geranium (Pelargonium spp.) essential oils and individual compounds against Stephanitis pyrioides and Aedes aegypti, Pest Management Sci 69, 1385-1392 (2013) 76) A Ali, N Tabanca, B Demirci, K.H.C Baser, J Ellis, S Gray, B.R Lackey, C Murphy, I.A Khan, D.E Wedge, Composition, mosquito larvicidal, biting deterrent and antifungal activity of essential oils of different plant parts of Cupressus arizonica var glabra ('Caroline Sapphire'), Nat Prod Commun 8(2) 257-260 (2013) 77) N Tabanca, U.R Bernier, A Ali, M Wang, B Demirci, E.K Blythe, S.I Khan, K.H.C Baser, I.A Khan, Bioassay-Guided Investigation of Two Monarda Essential oils for repellent activity against Yellow Fever mosquito Aedes aegypti, J Agric Food Chem 61 (36) 8573-8580 (2013) 78) Tabanca, M Kramer, N Elejalde, D Wedge, U Bernier, M Coy, J Becnel, B Demirci, K.H.C Baser, J Zhang, S Zhang, Sui, Activity of Cupressus funebris, Juniperus communis, and J chinensis (Cupressaceae) Essential Oils as Repellents against Ticks (Acari: Ixodidae) and as Repellents and Toxicants against Mosquitoes (Diptera: Culicidae), J Carroll, N J Vector Ecology, 36(2) 258-268 (2011) 79) D.E Wedge, N Tabanca, B J Sampson, C Werle, B Demirci, K.H.C Baser, P Nan, J Duan, Z Liu, Antifungal and insecticidal activity of two Juniperus essential oils, Nat Prod Com., 4(1) 123-127 (2009) 80) S Coskun, O Giriskin, M Kurkcuoglu, A.O Giriskin, N Kirimer, K.H.C Baser, Acaricidal efficacy of Origanum onites L essential oil againstRhipicephalus turanicus (Ixodidae), Parasitol Res., 103 ,259261 (2008) 14 81) B Ozdemir, A Ekbul, N.B Topal, E Sarandol, A Sag, K.H.C Baser, J Cordan, S Gullulu, E Tuncel, I Baran, A Aydinlar, Effects of Origanum onites on endothelial function and serum biochemical markers in hyperlipidaemic patients, J Int Med Res., 36, 1326-1334 (2008) 82) M Canbek, M Uyanoglu, G Bayramoglu, H Senturk, N Erkasap, T Koken, S Uslu, C Demirustu, E Aral, K.H.C Baser, Effects of carvacrol on defects of ischemia-reperfusion in the liver, Phytomedicine, 15, 447-452 (2008) 83) E Kupeli, F Goger, M Kosar, K H C Baser, Anti-inflammatory and Antinociceptive Activities of Salvia halophila andSalvia virgata from Turkey, Food Chem., 108, 942-949 (2008) 84) E Dundar, E.G Olgun, S Isiksoy, M Kurkcuoglu, K.H.C Baser, C Bal, The effects of intra-rectal and intra-peritoneal application of Origanum onites L Essential oil on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat, Exper.Toxicol Pathology, 59 (6) 399-408 (2008) 85) M Uyanoglu, M Canbek, E Aral, K.H.C Baser, Effects of carvacrol upon the liver of rats undergoing partial hepatectomy, , Phytomedicine, 15 , 226-229 (2008) 86) F Tosun, C Akyuz Kizilay, K Erol, F Sultan Kilic, M Kurkcuoglu, K H C Baser, Anticonvulsant activity of furanocoumarins and the essential oil obtained from the fruits of Heracleum crenatifolium, , Food Chem 107, 990-993 (2008) 15 ... Chromatotron and pilot plants and semi-industrial plants for large scale extraction and distillation, chemical reactor The laboratories possess all necessary facilities for essential oil research and. .. luminescence while alive When it is exposed to toxic chemicals it loses its luminesces and dies Bioluminex method measures the acute and chronic LD50 values of the tested samples Related references... companies interested in research and development, or by establishing a new company by the researcher himself There are ample opportunities for innovative researchers nowadays in many countries including