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Metabolic Engineering of Microbial Cell Factories for Biosynthesis of Flavonoids: a Review
molecules Review Metabolic Engineering of Microbial Cell Factories for Biosynthesis of Flavonoids: A Review Hanghang Lou 1,†, Lifei Hu 2,†, Hongyun Lu 1, Tianyu Wei 1 and Qihe Chen 1,* 1 Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310058, China; [email protected] (H.L.); [email protected] (H.L.); [email protected] (T.W.) 2 Hubei Key Lab of Quality and Safety of Traditional Chinese Medicine & Health Food, Huangshi 435100, China; [email protected] * Correspondence: [email protected]; Tel.: +86-0571-8698-4316 † These authors are equally to this manuscript. Abstract: Flavonoids belong to a class of plant secondary metabolites that have a polyphenol structure. Flavonoids show extensive biological activity, such as antioxidative, anti-inflammatory, anti-mutagenic, anti-cancer, and antibacterial properties, so they are widely used in the food, phar- maceutical, and nutraceutical industries. However, traditional sources of flavonoids are no longer sufficient to meet current demands. In recent years, with the clarification of the biosynthetic pathway of flavonoids and the development of synthetic biology, it has become possible to use synthetic metabolic engineering methods with microorganisms as hosts to produce flavonoids. This article mainly reviews the biosynthetic pathways of flavonoids and the development of microbial expression systems for the production of flavonoids in order to provide a useful reference for further research on synthetic metabolic engineering of flavonoids. Meanwhile, the application of co-culture systems in the biosynthesis of flavonoids is emphasized in this review. Citation: Lou, H.; Hu, L.; Lu, H.; Wei, Keywords: flavonoids; metabolic engineering; co-culture system; biosynthesis; microbial cell factories T.; Chen, Q. -
Diabetic Neuropathy)
A PROSPECTIVE OPEN LABELLED NON RANDOMIZED PHASE-II CLINICAL TRIAL OF “KADUKKAI CHOORANAM FOR “AKKINI SELATHUMAM” (DIABETIC NEUROPATHY) Dissertation submitted to THE TAMILNADU DR. MGR. MEDICAL UNIVERSITY CHENNAI-32 For the partial fulfillment of the requirements to the Degree of DOCTOR OF MEDICINE (SIDDHA) BRANCH-I DEPARTMENT OF POTHU MARUTHUVAM DEPARTMENT OF POTHU MARUTHUVAM GOVERNMENT SIDDHA MEDICAL COLLEGE PALAYAMKOTTAI - 627 002 TAMIL NADU, INDIA. OCTOBER 2019 GOVERNMENT SIDDHA MEDICAL COLLEGE PALAYAMKOTTAI - 627 002 TAMIL NADU, INDIA. BONAFIDE CERTIFICATE This is to certify that the dissertation entitled “A PROSPECTIVE OPEN LABELLED NON RANDOMIZED PHASE-II CLINICAL TRIAL OF “KADUKKAI CHOORANAM FOR AKKINI SELATHUMAM (DIABETIC NEUROPATHY)” is abonafide work done by Dr.RAJENDRAM AJANTHAN (Reg. No.321611008) Govt. Siddha Medical College, Palayamkottai - 627 002 in partial fulfilment of the university rules and regulations for award for MD (S) POTHU MARUTHUVAM (BRANCH-I) under my guidance and supervision during the academic year OCTOBER 2016-2019. Supervisor and Guide Prof. Dr.A.MANOHARAN, MD (S),( Ph.D). Head, Department of PothuMaruthuvam, Govt. Siddha Medical College, Palayamkottai. Name and signature of the HOD Name and signature of the Principal Prof. Dr. A.MANOHARAN, MD (S),( Ph.D). Prof. Dr.S.Victoria,MD(S) Dept. of PothuMaruthuvam, Govt. Siddha Medical College Govt. Siddha Medical College, Palayamkottai. Palayamkottai. GOVERNMENT SIDDHA MEDICAL COLLEGE PALAYAMKOTTAI - 627 002 TAMIL NADU, INDIA. CERTIFICATE Certified that I have gone through the dissertation entitled “A PROSPECTIVE OPEN LABELLED NON RANDOMIZED PHASE-II CLINICAL TRIAL OF “KADUKKAI CHOORANAM FOR AKKINI SELATHUMAM (DIABETIC NEUROPATHY)” submitted by Dr.RAJENDRAM AJANTHAN (Reg. No.321611008) a student of final year MD(S) Department of Pothu Maruthuvam (Branch-I)of this college and the dissertation work has been carried out by the individual only. -
Grape Seeds Proanthocyanidins: Advanced Technological Preparation and Analytical Characterization
antioxidants Article Grape Seeds Proanthocyanidins: Advanced Technological Preparation and Analytical Characterization Paolo Morazzoni 1, Paola Vanzani 2, Sandro Santinello 1, Antonina Gucciardi 2,3 , Lucio Zennaro 2, Giovanni Miotto 2,3,4,* and Fulvio Ursini 2,* 1 Distillerie Bonollo Umberto S.p.A., Nutraceutical Division, Mestrino, 35035 Padova, Italy; [email protected] (P.M.); [email protected] (S.S.) 2 Department of Molecular Medicine, University of Padova, 35129 Padova, Italy; [email protected] (P.V.); [email protected] (A.G.); [email protected] (L.Z.) 3 Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, 35129 Padova, Italy 4 CRIBI Biotechnology Center, University of Padova, 35129 Padova, Italy * Correspondence: [email protected] (G.M.); [email protected] (F.U.); Tel.: +39-0498276130 (G.M.); +39-0498276104 (F.U.) Abstract: A “green” solvent-free industrial process (patent pending) is here described for a grape seed extract (GSE) preparation (Ecovitis™) obtained from selected seeds of Veneto region wineries, in the northeast of Italy, by water and selective tangential flow filtration at different porosity. Since a comprehensive, non-ambiguous characterization of GSE is still a difficult task, we resorted to using an integrated combination of gel permeation chromatography (GPC) and electrospray ionization high resolution mass spectrometry (ESI-HRMS). By calibration of retention time and spectroscopic quantification of catechin as chromophore, we succeeded in quantifying GPC polymers up to traces at Citation: Morazzoni, P.; Vanzani, P.; n = 30. The MS analysis carried out by the ESI-HRMS method by direct-infusion allows the detection Santinello, S.; Gucciardi, A.; Zennaro, of more than 70 species, at different polymerization and galloylation, up to n = 13. -
Microclimatic Influences on Grape Quality
AusdemInstitutfürWeinanalytikundGetränkeforschung derHochschuleGeisenheimUniversity Prof.Dr.HelmutDietrich unddem InstitutfürPŇanzenbauundPŇanzenzüchtungII derJustusͲLiebigͲUniversitätGießen ProfessurfürBiometrieundPopulationsgenetik Prof.Dr.MatthiasFrisch Microclimaticinfluencesongrapequality Dissertation zurErlangungdesGradeseinesDoktors derAgrarwissenschaften imFachbereich Agrarwissenschaften,OekotrophologieundUmweltmanagement JustusͲLiebigͲUniversitätGießen Vorgelegtvon MatthiasFriedelausAlzenau Gießen,31.03.2017 Selbständigkeitserklärung Icherkläre:IchhabedievorgelegteDissertationselbständigundohneunerlaubte fremde Hilfe und nur mit den Hilfen angefertigt, die ich in der Dissertation angegebenhabe.AlleTextstellen,diewörtlichodersinngemäßausveröffentlichten Schriften entnommen sind, und alle Angaben, die auf mündlichen Auskünften beruhen,sindalssolchekenntlichgemacht.Beidenvonmirdurchgeführtenundin der Dissertation erwähnten Untersuchungen habe ich die Grundsätze guter wissenschaftlicher Praxis, wie sie in der „Satzung der JustusͲLiebigͲUniversität Gießen zur Sicherung guter wissenschaftlicher Praxis“ niedergelegt sind, eingehalten. Declarationofauthorship Ideclare: thisdissertationsubmittedisaworkof myown,writtenwithoutany illegitimate help by any third party and only with materials indicated in the dissertation. I have indicated in the text where I have used text from already publishedsources,eitherwordforwordorinsubstance,andwhereIhavemade statements based on oral information given to me. At any time during the investigationscarriedoutbymeanddescribedinthedissertation,Ifollowedthe -
Synthesis of Ochnaflavone and Its Inhibitory Activity on PGE 2
Synthesis and Biological Activity of Ochnaflavone Bull. Korean Chem. Soc. 2014, Vol. 35, No. 11 3219 http://dx.doi.org/10.5012/bkcs.2014.35.11.3219 Synthesis of Ochnaflavone and Its Inhibitory Activity on PGE2 Production Sung Soo Kim,† Van Anh Vo,† and Haeil Park* College of Pharmacy and †Medicine of Kangwon National University, Chuncheon 200-701, Korea *E-mail: [email protected] Received June 5, 2014, Accepted July 11, 2014 Ochnaflavone, a naturally occurring biflavonoid composed of two units of apigenin (5,7,4'-trihydroxyflavone) joined via a C-O-C linkage, was first synthesized and evaluated its inhibitory activity on PGE2 production. Total synthesis was accomplished through modified Ullmann diaryl ether formation as a key step. Coupling reactions of 4'-halogenoflavones and 3'-hydroxy-5,7,4'-trimethoxyflavone were explored in diverse reaction conditions. The reaction of 4'-fluoro-5,7-dimethoxyflavone (2c) and 3'-hydroxy-5,7,4'-trimethoxyflavone (2d) in N,N-dimethylacetamide gave the coupled compound 3 in 58% yield. Synthetic ochnaflavone strongly inhibited PGE2 production (IC50 = 1.08 µM) from LPS-activated RAW 264.7 cells, which was due to reduced expression of COX-2. On the contrary, the inhibition mechanism of wogonin was somewhat different from that of ochnaflavone although wogonin, a natural occurring anti-inflammatory flavonoid, showed strong inhibitory activity of PGE2 production (IC50 = 0.52 µM), and seems to be COX-2 enzyme inhibition. Our concise total synthesis of ochnaflavone enable us to provide sufficient quantities of material for advanced biological studies as well as to efficiently prepare derivatives for structure-activity relationship study. -
Antioxidant Capacities and Phenolic Levels of Different Varieties of Serbian White Wines
Molecules 2010, 15, 2016-2027; doi:10.3390/molecules15032016 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Antioxidant Capacities and Phenolic Levels of Different Varieties of Serbian White Wines Milan N. Mitić, Mirjana V. Obradović, Zora B. Grahovac and Aleksandra N. Pavlović * Faculty of Sciences and Mathematics, Department of Chemistry, University of Niš, Višegradska 33, P.O.Box 224, 18000 Niš, Serbia; E-Mails: [email protected](M.N.M.); [email protected] (M.V.O.); [email protected] (Z.B.G.) ∗ Author to whom correspondence should be addressed; E-Mail: [email protected]. Received: 22 January 2010; in revised form: 23 February 2010 / Accepted: 9 March 2010 / Published: 22 March 2010 Abstract: The biologically active compounds in wine, especially phenolics, are responsible for reduced risk of developing chronic diseases (cardiovascular disrease, cancer, diabetes, etc.), due to their antioxidant activities. We determined the contents of total phenolics (TP) and total flavonoids (TF) in selected Serbian white wines by colorimetric methods. Total antioxidant activity (TAA) of the white wines was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay. Međaš beli had the highest content of TP, TF and TAA. The radical scavenging capacity (RSC) and total antioxidant activity (TAA) of white wines were 15.30% and 1.055 mM Trolox equivalent, respectively. Total phenolic (TP) and total flavonoid (TF) contents in white wines ranged from 238.3 to 420.6 mg gallic acid equivalent per L of wines and 42.64 to 81.32 mg catechin equivalent per L of wines, respectively. -
Chemical Structures of Lignans and Neolignans Isolated from Lauraceae
Review Chemical Structures of Lignans and Neolignans Isolated from Lauraceae Ya Li 1,*, Shuhan Xie 2, Jinchuan Ying 1, Wenjun Wei 1 and Kun Gao 1,* 1 State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China; [email protected] (J.Y.); [email protected] (W.W.) 2 Lanzhou University High School, Lanzhou 730000, China; [email protected] * Correspondences: [email protected] (Y.L.); [email protected] (K.G.); Tel.: +86-931-8912500 (Y.L.) Academic Editor: David Barker Received: 09 November 2018; Accepted: 29 November 2018; Published: 30 November 2018 Abstract: Lauraceae is a good source of lignans and neolignans, which are the most chemotaxonomic characteristics of many species of the family. This review describes 270 naturally occurring lignans and neolignans isolated from Lauraceae. Keywords: lignans; neolignans; Lauraceae; chemical components; chemical structures 1. Introduction Lignans are widely distributed in the plant kingdom, and show diverse pharmacological properties and a great number of structural possibilities. The Lauraceae family, especially the genera of Machilus, Ocotea, and Nectandra, is a rich source of lignans and neolignans, and neolignans represent potential chemotaxonomic significance in the study of the Lauraceae. Lignans and neolignans are dimers of phenylpropane, and conventionally classified into three classes: lignans, neolignans, and oxyneolignans, based on the character of the C–C bond and oxygen bridge joining the two typical phenyl propane units that make up their general structures [1]. Usually, lignans show dimeric structures formed by a β,β’-linkage (8,8’-linkage) between two phenylpropanes units. Meanwhile, the two phenylpropanes units are connected through a carbon–carbon bond, except for the 8,8’-linkage, which gives rise to neolignans. -
Importance of the 4-Substituted Resorcinol Moiety
International Journal of Molecular Sciences Article Urolithin and Reduced Urolithin Derivatives as Potent Inhibitors of Tyrosinase and Melanogenesis: Importance of the 4-Substituted Resorcinol Moiety Sanggwon Lee 1,†, Heejeong Choi 1,† , Yujin Park 1, Hee Jin Jung 1 , Sultan Ullah 2, Inkyu Choi 1, Dongwan Kang 1, Chaeun Park 1, Il Young Ryu 1, Yeongmu Jeong 1, YeJi Hwang 1, Sojeong Hong 1, Pusoon Chun 3 and Hyung Ryong Moon 1,* 1 College of Pharmacy, Pusan National University, Busan 46241, Korea; [email protected] (S.L.); [email protected] (H.C.); [email protected] (Y.P.); [email protected] (H.J.J.); [email protected] (I.C.); [email protected] (D.K.); [email protected] (C.P.); [email protected] (I.Y.R.); [email protected] (Y.J.); [email protected] (Y.H.); [email protected] (S.H.) 2 Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA; [email protected] 3 College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-51-510-2815; Fax: +82-51-513-6754 † These authors (S. Lee and H. Choi) contributed equally to this work. Abstract: We previously reported (E)-β-phenyl-α,β-unsaturated carbonyl scaffold ((E)-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4- Citation: Lee, S.; Choi, H.; Park, Y.; substituted resorcinol moiety as the β-phenyl group of the scaffold resulted in the greatest tyrosinase Jung, H.J.; Ullah, S.; Choi, I.; Kang, D.; inhibitory activity. -
Novel Bioactive Extraction and Nano-Encapsulation
Entry Novel Bioactive Extraction and Nano-Encapsulation Shaba Noore 1,2 , Navin Kumar Rastogi 3, Colm O’Donnell 2 and Brijesh Tiwari 1,2,* 1 Department of Food Chemistry & Technology, Teagasc Food Research Centre, Ashtown, D15 DY05 Dublin, Ireland; [email protected] 2 School of Biosystems and Food Engineering, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland; [email protected] 3 Department of Food Engineering, CSIR-Central Food Technological Research Institute, Mysuru 570020, India; [email protected] * Correspondence: [email protected] Definition: An extraction technology works on the principle of two consecutive steps that involves mixture of solute with solvent and the movement of soluble compounds from the cell into the solvent and its consequent diffusion and extraction. The conventional extraction techniques are mostly based on the use of mild/high temperatures (50–90 ◦C) that can cause thermal degradation, are dependent on the mass transfer rate, being reflected on long extraction times, high costs, low extraction efficiency, with consequent low extraction yields. Due to these disadvantages, it is of interest to develop non-thermal extraction methods, such as microwave, ultrasounds, supercritical fluids (mostly using carbon dioxide, SC-CO2), and high hydrostatic pressure-assisted extractions which works on the phenomena of minimum heat exposure with reduced processing time, thereby minimizing the loss of bioactive compounds during extraction. Further, to improve the stability of these extracted compounds, nano-encapsulation is required. Nano-encapsulation is a process which forms a thin layer of protection against environmental degradation and retains the nutritional and Citation: Noore, S.; Rastogi, N.K.; functional qualities of bioactive compounds in nano-scale level capsules by employing fats, starches, O’Donnell, C.; Tiwari, B. -
Glycosides Pharmacognosy Dr
GLYCOSIDES PHARMACOGNOSY DR. KIBOI Glycosides Glycosides • Glycosides consist of a sugar residue covalently bound to a different structure called the aglycone • The sugar residue is in its cyclic form and the point of attachment is the hydroxyl group of the hemiacetal function. The sugar moiety can be joined to the aglycone in various ways: 1.Oxygen (O-glycoside) 2.Sulphur (S-glycoside) 3.Nitrogen (N-glycoside) 4.Carbon ( Cglycoside) • α-Glycosides and β-glycosides are distinguished by the configuration of the hemiacetal hydroxyl group. • The majority of naturally-occurring glycosides are β-glycosides. • O-Glycosides can easily be cleaved into sugar and aglycone by hydrolysis with acids or enzymes. • Almost all plants that contain glycosides also contain enzymes that bring about their hydrolysis (glycosidases ). • Glycosides are usually soluble in water and in polar organic solvents, whereas aglycones are normally insoluble or only slightly soluble in water. • It is often very difficult to isolate intact glycosides because of their polar character. • Many important drugs are glycosides and their pharmacological effects are largely determined by the structure of the aglycone. • The term 'glycoside' is a very general one which embraces all the many and varied combinations of sugars and aglycones. • More precise terms are available to describe particular classes. Some of these terms refer to: 1.the sugar part of the molecule (e.g. glucoside ). 2.the aglycone (e.g. anthraquinone). 3.the physical or pharmacological property (e.g. saponin “soap-like ”, cardiac “having an action on the heart ”). • Modern system of naming glycosides uses the termination '-oside' (e.g. sennoside). • Although glycosides form a natural group in that they all contain a sugar unit, the aglycones are of such varied nature and complexity that glycosides vary very much in their physical and chemical properties and in their pharmacological action. -
Photodynamic Therapy for Cancer Role of Natural Products
Photodiagnosis and Photodynamic Therapy 26 (2019) 395–404 Contents lists available at ScienceDirect Photodiagnosis and Photodynamic Therapy journal homepage: www.elsevier.com/locate/pdpdt Review Photodynamic therapy for cancer: Role of natural products T Behzad Mansooria,b,d, Ali Mohammadia,d, Mohammad Amin Doustvandia, ⁎ Fatemeh Mohammadnejada, Farzin Kamaric, Morten F. Gjerstorffd, Behzad Baradarana, , ⁎⁎ Michael R. Hambline,f,g, a Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran b Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran c Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran d Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, 5000, Odense, Denmark e Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA f Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA g Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA ARTICLE INFO ABSTRACT Keywords: Photodynamic therapy (PDT) is a promising modality for the treatment of cancer. PDT involves administering a Photodynamic therapy photosensitizing dye, i.e. photosensitizer, that selectively accumulates in tumors, and shining a light source on Photosensitizers the lesion with a wavelength matching the absorption spectrum of the photosensitizer, that exerts a cytotoxic Herbal medicine effect after excitation. The reactive oxygen species produced during PDT are responsible for the oxidation of Natural products biomolecules, which in turn cause cell death and the necrosis of malignant tissue. PDT is a multi-factorial process that generally involves apoptotic death of the tumor cells, degeneration of the tumor vasculature, stimulation of anti-tumor immune response, and induction of inflammatory reactions in the illuminated lesion.