DOCSLIB.ORG

Docking Characterization and in Vitro Inhibitory Activity of Flavan-3-Ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Docking Characterization and in Vitro Inhibitory Activity of Flavan-3-Ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2 ORIGINAL RESEARCH published: 30 November 2020 doi: 10.3389/fpls.2020.601316 Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2 Yue Zhu and De-Yu Xie* Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC, United States We report to use the main protease (Mpro) of SARS-Cov-2 to screen plant flavan-3-ols and proanthocyanidins. Twelve compounds, (–)-afzelechin (AF), (–)-epiafzelechin (EAF), (+)-catechin (CA), (–)-epicatechin (EC), (+)-gallocatechin (GC), (–)-epigallocatechin Edited by: (EGC), (+)-catechin-3-O-gallate (CAG), (–)-epicatechin-3-O-gallate (ECG), Guodong Wang, Chinese Academy of Sciences, China (–)-gallocatechin-3-O-gallate (GCG), (–)-epigallocatechin-3-O-gallate (EGCG), Reviewed by: procyanidin A2 (PA2), and procyanidin B2 (PB2), were selected for docking simulation. pro Hiroshi Noguchi, The resulting data predicted that all 12 metabolites could bind to M . The affinity Nihon Pharmaceutical scores of PA2 and PB2 were predicted to be −9.2, followed by ECG, GCG, EGCG, University, Japan Ericsson Coy-Barrera, and CAG, −8.3 to −8.7, and then six flavan-3-ol aglycones, −7.0 to −7.7. Docking Universidad Militar Nueva characterization predicted that these compounds bound to three or four subsites (S1, Granada, Colombia S1′, S2, and S4) in the binding pocket of Mpro via different spatial ways and various *Correspondence: De-Yu Xie formation of one to four hydrogen bonds. In vitro analysis with 10 available compounds pro [email protected] showed that CAG, ECG, GCG, EGCG, and PB2 inhibited the M activity with an IC50 value, 2.98 ± 0.21, 5.21 ± 0.5, 6.38 ± 0.5, 7.51 ± 0.21, and 75.3 ± 1.29 µM, Specialty section: respectively, while CA, EC, EGC, GC, and PA2 did not have inhibitory activities. To This article was submitted to Plant Metabolism and Chemodiversity, further substantiate the inhibitory activities, extracts prepared from green tea (GT), two a section of the journal muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, Frontiers in Plant Science GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed Received: 31 August 2020 pro Accepted: 06 November 2020 that GT, two MG, cacao, and DC extracts inhibited the M activity with an IC50 value, Published: 30 November 2020 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 µg/ml, Citation: respectively. These findings indicate that on the one hand, the structural features of Zhu Y and Xie D-Y (2020) Docking flavan-3-ols are closely associated with the affinity scores; on the other hand, the Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory Proanthocyanidins Against the Main activity against the Mpro activity. Protease Activity of SARS-Cov-2. Front. Plant Sci. 11:601316. Keywords: flavan-3-ols, flavan-3-ol gallates, procyanidins, COVID-19, green tea, muscadine grape, cacao, dark doi: 10.3389/fpls.2020.601316 chocolate Frontiers in Plant Science | www.frontiersin.org 1 November 2020 | Volume 11 | Article 601316 Zhu and Xie Flavan-3-ols and Proanthocyanidins Against SARS-Cov-2 INTRODUCTION patients (Dai W. et al., 2020; Zhang et al., 2020). Currently, the humans are placing a hope on vaccines. However, no effective SARS-CoV-2 is a novel severe acute respiratory syndrome-related vaccines are ready for prevention. The potential risks of vaccines coronavirus strain and highly contagious to humans (Figure 1). remain largely unknown. Making matters worse, more studies Its infection on humans was reported in the early December have shown that the originality and the transmission of this of 2019 in Wuhan, China (Wang C. et al., 2020; Wu et al., contagious virus are more complicated than the humans know. 2020). On January 30, 2020, The World Health Organization Studies have shown that in addition to aerosol transmission, (WHO) declared the outbreak of the coronavirus disease 2019 this virus can be transmitted through gastrointestinal infection (COVID-19) emergency (World Health Organization, 2020a). (Lamers et al., 2020; Xiao et al., 2020) and can stably stay for 3h On March 11, 2020, WHO announced the COVID-19 pandemic in air and 72h on plastic and steal surfaces (van Doremalen et al., (World Health Organization, 2020b). As of October 22, 2020, 2020). In addition to causing lung diseases, this virus has been it has infected ∼41,561,983 people and caused ∼1,135,289 found to cause other health complications, such as abdominal deaths worldwide (data source from Johns Hopkins Coronavirus pain (Lamers et al., 2020) and neurologic abnormality (Helms Resource Center). These numbers are continuously increasing et al., 2020). To the whole world surprise, one newest study every day. Extremely sadly, the humans do not know when this revealed that SARS-Cov-2 existed in wastewater that had been pandemic will end. Although hydroxychloroquine, chloroquine, stored in Barcelona, Spain since March 2019 (Chavarria-Miró and remdesivir were recommended for treating COVID-19 et al., 2020), the time of which was 9 months earlier than the (Colson et al., 2020; Sehailia and Chemat, 2020; Wang M. first report from Wuhan. This finding implies that SARS-Cov- et al., 2020), their therapeutic effects still remain for studies. For 2 might have been transmitted in humans before the outbreak. In example, a new study showed that chloroquine could not treat summary, no medicines can treat COVID-19 and no vaccines can COVID-19 (Hoffmann et al., 2020). Although 300 trials with prevent this contagious disease. Therefore, effective treatments different anti-virus medicines are being performed (Sanders et al., and preventions are urgently needed. 2020), such as lopinavir and ritonavir (Cao et al., 2020), the fact Flavan-3-ols and proanthocyanidins (PAs) are two groups is that no medicines show therapeutic effectiveness. Although in of plant flavonoids (Figure 2; Xie and Dixon, 2005). They June 2020, dexamethasone, a steroid, was publically reported to commonly exist in fruits, food products, and beverages, such decrease the death risk of COVID-19 patients (Khan and Htar, as grape (Iacopini et al., 2008; Zhu et al., 2014; Yuzuak et al., 2020; Selvaraj et al., 2020), more trials need to be performed to 2018; Rousserie et al., 2019), strawberry (Lopez-Serrano and demonstrate its effectiveness. Furthermore, different proteins or Barcelo, 1997; Fossen et al., 2004; Fischer et al., 2014), persimmon genes of SARS-Cov-2, such as the main protease (Figure 1), have (Akagi et al., 2009), cranberry (Foo et al., 2000a,b), blueberry been targeted to screen medicines, however, no small molecules (Gu et al., 2002), cacao nuts (Murphy et al., 2003; Miller et al., have been conclusively shown to be able to treat COVID-19 2009), chocolate (Schewe et al., 2002; Serafini et al., 2003), FIGURE 1 | A simplified diagram showing the essential function of the main protease involved in SARS-Cov-2 replication in infected host cells. Frontiers in Plant Science | www.frontiersin.org 2 November 2020 | Volume 11 | Article 601316 Zhu and Xie Flavan-3-ols and Proanthocyanidins Against SARS-Cov-2 FIGURE 2 | Structures of (+)-afzelechin, (–)-epiafzelechin, (+)-catechin, (–)-epicatechin, (+)-gallocatechin, (–)-epigallocatechin, (–)-catechin-3-O-gallate, (–)-epicatechin-3-O-gallate, (–)-gallocatechin-3-O-gallate, and (–)-epigallocatechin-3-O-gallate, procyanidin B1 and B2, and procyanidin A1 and A2. green tea (Liu et al., 2012; Zhao et al., 2017; Wang P. et al., two types of structures, the dominant B-type characterized with 2020), and wines (Monagas et al., 2003). Common flavan-3- an interflavan bond only and the uncommon A-type featured ol aglycones in these plant products include (–)-epicatechin with an interflavan bond and an ether linkage (Xie and Dixon, (EC), (+)-catechin (CA), (–)-epigallocatechin (EGC), (+)- 2005). Common dimeric B-types in fruits and beverages include gallocatechin (GC), (–)-epiafzelechin (EAF), and (+)-afzelechin procyanidin B1, B2, B3, and B4. Two examples of dimeric A- (AF) (Figure 2; Xie and Dixon, 2005). Common flavan-3- type PAs are procyanidin A1 and A2 (Xie and Dixon, 2005). ol gallates include (–)-epicatechin-3-O-gallate (ECG), (+)- Flavan-3-ols and PAs are potent antioxidants with multiple catechin-3-O-gallate (CAG), (–)-gallatechin-3-O-gallate (GCG), benefits to human health (Xie and Dixon, 2005). Multiple (–)-epigallocatechin-3-O-galloate (EGCG), which are highly compounds from these two groups, such as CA, EPC, EGC, abundant in green tea (Dai X. et al., 2020; Wang P. et al., EGCG, procyanidin B2, and procyanidin A2 (Figure 2), have 2020). PAs are oligomeric or polymeric flavan-3-ols. In PAs, been shown to have antiviral function (de Bruyne et al., 1999; the lowest and upper units are termed as the starter and Iwasawa et al., 2009), antibacterial activity (Molan et al., 2001; extension units, which are linked by interflavan bonds formed Howell et al., 2005), anticancer (Ohata et al., 2005; Suganuma between the C8 or C6 of a lower unit and the C4 of an et al., 2011), anti-cardiovascular diseases (Loke et al., 2008; upper unit (Figure 2). In addition, a second linkage is a C2- Panneerselvam et al., 2010; MacRae et al., 2019), and anti-aging O-C7 ether bond between the starter unit and the extension diseases (Levites et al., 2003; Li et al., 2004; Weinreb et al., 2004). unit. Based on the linkage numbers, PAs are classified into In particular, the anti-viral activity suggests that flavan-3-ols and Frontiers in Plant Science | www.frontiersin.org 3 November 2020 | Volume 11 | Article 601316 Zhu and Xie Flavan-3-ols and Proanthocyanidins Against SARS-Cov-2 PAs are appropriate targets for screening potential anti-SARS- hydrogens were added and receptor charge was optimized, Cov-2 medicines.
Load more

Recommended publications
  • Proanthocyanidin Metabolism, a Mini Review
    Nutrition and Aging 2 (2014) 111–116 111 DOI 10.3233/NUA-140038 IOS Press Proanthocyanidin Metabolism, a mini review Y.Y. Choy and A.L. Waterhouse∗ Viticulture and Enology, University of California, Davis, CA, USA Abstract. There is emerging evidence suggesting that consumption of beverage and food rich in polyphenol may offer protective effects against various neurodegenerative, cardiovascular diseases and cancers. Proanthocyanidins (PACs) are one of the most abundant polyphenol in human diets, but also one of the least absorbed polyphenol mostly due to their size and structure com- plexity. PACs or condensed tannins are oligomers and polymers of monomeric unit flavan-3-ol (+)-catechin or (−)-epicatechin. To date, the absorption and metabolism of PACs are still remains largely unknown. The aim of this mini review was to highlight the absorption and metabolism of PACs, their effect in the gut and sample preparation for analysis. Ultimately, the potential bioactivities derived from the interaction between PACs metabolites and the gut microbiota warrants further investigation. Keywords: Proanthocyanidins, phenolic acids, metabolism, colon 1. Introduction derived subunits. PACs that consists exclusively of (−)-epicatechin, (+)-catechin units, are known as pro- Polyphenols are among the ubiquitous constituents cyanidins because only cyanidin is released in acid, of foods of plant origins and are widely distributed and comprised the largest class of PACs, while those throughout the plant kingdom. Polyphenols can be with gallocatechin units release delphinidin. The size categorized into different groups such as flavonoids, or molecular weight of PACs can be expressed as phenolic acids, stilbenes and lignans. The flavonoids mean degree of polymerization (mDP).
    [Show full text]
  • Food & Function
    Food & Function View Article Online REVIEW View Journal | View Issue Roles of proanthocyanidin rich extracts in obesity Cite this: Food Funct., 2015, 6, 1053 M. Josepa Salvadó,* Ester Casanova, Anabel Fernández-Iglesias, Lluis Arola and Cinta Bladé Obesity is a multifactorial disorder involving an abnormal or excessive amount of body fat. Obese people have a very high probability of developing metabolic syndrome, a condition in which cholesterol, lipid, and glucose levels rise, causing diabetes and heart disease. From the point of view of energy balance, the main contributors to obesity are excessive energy intake, inadequate energy expenditure and metabolic malfunctions. For this reason, health organisations are working to implement policies and plans to promote healthy eating and active living. However, these measures have not yet proven sufficient to combat this worldwide epidemic; therefore, drugs and bioactive compounds are being investigated to complement the existing strategies. In the present review, we discuss the available data regarding the Received 13th November 2014, modulation of obesity by proanthocyanidin rich extracts. Because studies with human subjects are very Accepted 22nd January 2015 scarce, we focus on studies using laboratory animals. The results of in vitro studies are included because, Creative Commons Attribution-NonCommercial 3.0 Unported Licence. DOI: 10.1039/c4fo01035c although they cannot be directly extrapolated to the biological effects of proanthocyanidin, they can www.rsc.org/foodfunction reveal some mechanisms
    [Show full text]
  • Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: in Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary
    nutrients Article Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: In Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary Flavonoids 1,2, 2, , 1 1 1 Hiroki Saito y, Yu Toyoda * y , Hiroshi Hirata , Ami Ota-Kontani , Youichi Tsuchiya , Tappei Takada 2 and Hiroshi Suzuki 2 1 Frontier Laboratories for Value Creation, Sapporo Holdings Ltd., 10 Okatome, Yaizu, Shizuoka 425-0013, Japan; [email protected] (H.S.); [email protected] (H.H.); [email protected] (A.O.-K.); [email protected] (Y.T.) 2 Department of Pharmacy, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; [email protected] (T.T.); [email protected] (H.S.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 2 July 2020; Accepted: 12 August 2020; Published: 14 August 2020 Abstract: Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands—the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S—an ABCC11 substrate).
    [Show full text]
  • Different Approaches to Evaluate Tannin Content and Structure of Selected Plant Extracts – Review and New Aspects M
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by JKI Open Journal Systems (Julius Kühn-Institut) Journal of Applied Botany and Food Quality 86, 154 - 166 (2013), DOI:10.5073/JABFQ.2013.086.021 1University of Kiel, Institute of Crop Science and Plant Breeding – Grass and Forage Science / Organic Agriculture, Kiel, Germany 2Institute of Ecological Chemistry, Plant Analysis and Stored Product Protection; Julius Kühn-Institute, Quedlinburg, Germany Different approaches to evaluate tannin content and structure of selected plant extracts – review and new aspects M. Kardel1*, F. Taube1, H. Schulz2, W. Schütze2, M. Gierus1 (Received July 2, 2013) Summary extracts, tannins, salts and derivates was imported to the EU in the year 2011, mainly from Argentina, with a trade value of nearly Tannins occur in many field herbs and legumes, providing an im- 63.5 mio. US Dollar (UN-COMTRADE, 2013). These extracts are pro- mense variability in structure and molecular weight. This leads to duced industrially on a large scale. They could therefore maintain complications when measuring tannin content; comparability of a relatively constant quality and thus provide an advantage in rumi- different methods is problematic. The present investigations aimed at nant feeding. characterizing four different tannin extracts: quebracho (Schinopsis Tannins from different sources can react very diverse regarding lorentzii), mimosa (Acacia mearnsii), tara (Caesalpinia spinosa), protein affinity (MCNABB et al., 1998; BUENO et al., 2008). Diffe- and gambier (Uncaria gambir) and impact of storage conditions. rences in tannin structure can occur even between similar plant Using photometrical methods as well as HPLC-ESI-MS, fundamen- species (OSBORNE and MCNEILL, 2001; HATTAS et al., 2011) and a tal differences could be determined.
    [Show full text]
  • Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties
    Downloaded from orbit.dtu.dk on: Sep 30, 2021 Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties Dudnik, Alexey; Gaspar, Paula; Neves, Ana Rute; Forster, Jochen Published in: Current Pharmaceutical Design Link to article, DOI: 10.2174/1381612824666180515152049 Publication date: 2018 Document Version Peer reviewed version Link back to DTU Orbit Citation (APA): Dudnik, A., Gaspar, P., Neves, A. R., & Forster, J. (2018). Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial Properties. Current Pharmaceutical Design, 24(19), 2208-2225. https://doi.org/10.2174/1381612824666180515152049 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. 1 TITLE 2 Engineering of Microbial Cell Factories for the Production of Plant Polyphenols with Health-Beneficial 3 Properties 4 RUNNING TITLE 5 Microbial production of polyphenols 6 7 AUTHORS 8 Alexey Dudnik1,#,*, Paula Gaspar1,3,#, Ana Rute Neves2 and Jochen Forster1 9 10 1 Applied Metabolic Engineering Group, The Novo Nordisk Foundation Center for Biosustainability, 11 Technical University of Denmark, Kemitorvet, Building 220, DK-2800, Kgs.
    [Show full text]
  • Epigallocatechin Gallate: a Review
    Veterinarni Medicina, 63, 2018 (10): 443–467 Review Article https://doi.org/10.17221/31/2018-VETMED Epigallocatechin gallate: a review L. Bartosikova*, J. Necas Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic *Corresponding author: [email protected] ABSTRACT: Epigallocatechin gallate is the major component of the polyphenolic fraction of green tea and is responsible for most of the therapeutic benefits of green tea consumption. A number of preclinical in vivo and in vitro experiments as well as clinical trials have shown a wide range of biological and pharmacological properties of polyphenolic compounds such as anti-oxidative, antimicrobial, anti-allergic, anti-diabetic, anti-inflammatory, anti-cancer, chemoprotective, neuroprotective and immunomodulatory effects. Epigallocatechin gallate controls high blood pressure, decreases blood cholesterol and body fat and decreases the risk of osteoporotic fractures. Further research should be performed to monitor the pharmacological and clinical effects of green tea and to more clearly elucidate its mechanisms of action and the potential for its use in medicine. Keywords: epigallocatechin-3-O-gallate; pharmacokinetics; toxicity; biological activity List of abbreviations ADME = absorption, distribution, metabolism, excretion; AMP = activated protein kinase (AMPK); AUC (0–∞) = area under the concentration-time curve from 0 h to infinity; BAX = apoptosis regulator (pro-apoptotic regulator, known as bcl-2-like protein 4); Bcl-2 = B-cell lymphoma 2; BCL-XL = B-cell
    [Show full text]
  • 2019, 17–28 Assessment of Antioxidants by Hplc-Ms in Grapevine Seeds
    Acta Sci. Pol. Hortorum Cultus, 18(6) 2019, 17–28 https://czasopisma.up.lublin.pl/index.php/asphc ISSN 1644-0692 e-ISSN 2545-1405 DOI: 10.24326/asphc.2019.6.2 ORIGINAL PAPER Accepted: 4.03.2019 ASSESSMENT OF ANTIOXIDANTS BY HPLC-MS IN GRAPEVINE SEEDS Lenka Sochorova1, Borivoj Klejdus2, Mojmir Baron1, Tunde Jurikova3, Jiri Mlcek4, Jiri Sochor1, Sezai Ercisli5, Muhammed Kupe5 1 Department of Viticulture and Enology, Faculty of Horticulture, Mendel University in Brno, Valticka 337, CZ-691 44 Lednice, Czech Republic 2 Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic 3 Department of Natural and Informatics Sciences, Faculty of Central European Studies, Constantine the Philosopher University in Nitra, Drazovska 4, 949 74 Nitra, Slovakia 4 Department of Food Analysis and Chemistry, Faculty of Technology, Tomas Bata University in Zlin, nam. T. G. Masaryka 5555, 760 01 Zlin Czech Republic 5 Department of Horticulture, Agricultural Faculty, Ataturk University, 25240 Erzurum, Turkey ABSTRACT It is well known, that grapevine seeds are rich in significant antioxidants. However, the issue of dealing with the analysis and comparison of antioxidant components in the seeds of Vitis vinifera L. in individual cultivars has not yet been sufficiently studied. The experiment was performed with extracts of three varieties (Blaufränkish, Italian Riesling and Cabernet Moravia) and three interspecific cultivars (Nativa, Marlen and Kofranka). Contents of nine major flavonoids (apigenin, astragalin, hyperoside, isorhamnetin, kaempferol, myricetin, quercetin, quercitrin and rutin) and two procyanidins (procyanidin A2 and procyanidin B1) were assessed by the HPLC/MS method.
    [Show full text]
  • Influence of COMT Genotype Polymorphism on Plasma and Urine
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Minnesota Digital Conservancy Influence of COMT Genotype Polymorphism on Plasma and Urine Green Tea Catechin Levels in Postmenopausal Women A THESIS SUBMITTED TO THE FACULTY OF THE UNIVERSITY OF MINNESOTA BY Alyssa Heather Perry IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE Dr. Mindy Kurzer September 2014 © Alyssa Heather Perry 2014 Abstract Catechins are the major polyphenolic compound in green tea that have been investigated extensively over the past few decades in relation to the treatment of various chronic diseases including diabetes, cardiovascular disease, and cancer. O-methylation is a major Phase II metabolic pathway of green tea catechins (GTCs) via the enzyme catechol-O- methyltransferase (COMT). A single nucleotide polymorphism in the gene coding for COMT leads to individuals with a high-, intermediate-, or low-activity COMT enzyme. An epidemiological case-control study suggests that green tea consumption is associated with reduced risk of breast cancer in women with an intermediate- or low-activity COMT genotype. A cross-sectional analysis discovered that men homozygous for the low- activity COMT genotype showed a reduction in total tea polyphenols in spot urine samples compared to the intermediate- and high-activity genotypes. Several human intervention trials have assessed green tea intake, metabolism, and COMT genotype with conflicting results. The aim of the present study was to determine if the COMT polymorphism would modify the excretion and plasma levels of GTCs in 180 postmenopausal women at high risk for breast cancer consuming a green tea extract supplement containing 1222 mg total catechins daily for 12 months.
    [Show full text]
  • Polymerization Degrees, Molecular Weights and Protein-Binding Affinities of Condensed Tannin Fractions from a Leucaena Leucocephala Hybrid
    Molecules 2014, 19, 7990-8010; doi:10.3390/molecules19067990 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Polymerization Degrees, Molecular Weights and Protein-Binding Affinities of Condensed Tannin Fractions from a Leucaena leucocephala Hybrid Mookiah Saminathan 1, Hui Yin Tan 2, Chin Chin Sieo 1,3, Norhani Abdullah 3,4, Clemente Michael Vui Ling Wong 5, Emilia Abdulmalek 6 and Yin Wan Ho 1,* 1 Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; E-Mails: [email protected] (M.S.); [email protected] (C.C.S.) 2 Faculty of Applied Sciences and Computing, Tunku Abdul Rahman University College, 53300 Kuala Lumpur, Malaysia; E-Mail: [email protected] 3 Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; E-Mail: [email protected] 4 Institute of Tropical Agriculture, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia 5 Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia; E-Mail: [email protected] 6 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +603-8947-2161; Fax: +603-8947-2101. Received: 18 March 2014; in revised form: 11 May 2014 / Accepted: 21 May 2014 / Published: 12 June 2014 Abstract: Condensed tannins (CTs) form insoluble complexes with proteins and are able to protect them from degradation, which could lead to rumen bypass proteins. Depending on their degrees of polymerization (DP) and molecular weights, CT fractions vary in their capability to bind proteins.
    [Show full text]
  • UC Santa Barbara Dissertation Template
    UNIVERSITY OF CALIFORNIA Santa Barbara A-type Procyanidins and Their Effects on the Aggregation of Tau Prevalent in Alzheimer’s Disease A Thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Biochemistry and Molecular Biology by Michael James Weingart Committee in charge: Professor John Lew, Chair Professor Rolf E. Christoffersen Professor Benjamin E. Reese January 2018 The thesis of Michael James Weingart is approved. ________________________________________ Benjamin E. Reese ________________________________________ Rolf E. Christoffersen ________________________________________ John Lew, Committee Chair January 2018 A-type Procyanidins and Their Effects on the Aggregation of Tau Prevalent in Alzheimer’s Disease Copyright © 2018 by Michael James Weingart iii Acknowledgements Thank you to Professor John Lew and Dylan Peterson for welcoming me into the lab, for giving me the opportunity to work on this project in the first place, and for teaching me pretty much everything I know about lab work. Thank you to Professors Ben Reese and Rolf Christoffersen for taking time out of their schedules to serve on my committee. And thank you to my parents for always being supportive no matter what I decided to pursue. iv Abstract A-type Procyanidins and Their Effects on the Aggregation of Tau Prevalent in Alzheimer’s Disease by Michael James Weingart Alzheimer’s disease (AD) affects over 40 million people worldwide: a number that is expected to grow to over 100 million by 2050.1 Despite this, there is a shortage of AD drugs on the market, with only five having been FDA approved, and no new ones since 2003.2 A major problem is that these drugs are merely symptomatic treatments.
    [Show full text]
  • Masquelier's Grape Seed Extract: from Basic Flavonoid Research to a Well
    Weseler and Bast Nutrition Journal (2017) 16:5 DOI 10.1186/s12937-016-0218-1 REVIEW Open Access Masquelier’s grape seed extract: from basic flavonoid research to a well-characterized food supplement with health benefits Antje R. Weseler* and Aalt Bast Abstract Careful characterization and standardization of the composition of plant-derived food supplements is essential to establish a cause-effect relationship between the intake of that product and its health effect. In this review we follow a specific grape seed extract containing monomeric and oligomeric flavan-3-ols from its creation by Jack Masquelier in 1947 towards a botanical remedy and nutraceutical with proven health benefits. The preparation’s research history parallels the advancing insights in the fields of molecular biology, medicine, plant and nutritional sciences during the last 70 years. Analysis of the extract’s flavanol composition emerged from unspecific colorimetric assays to precise high performance liquid chromatography - mass spectrometry and proton nuclear magnetic resonance fingerprinting techniques. The early recognition of the preparation’s auspicious effects on the permeability of vascular capillaries directed research to unravel the underlying cellular and molecular mechanisms. Recent clinical data revealed a multitude of favorable alterations in the vasculature upon an 8 weeks supplementation whichsummedupinahealthbenefitoftheextractin healthy humans. Changes in gene expression of inflammatory pathways in the volunteers’ leukocytes were suggested to be involved
    [Show full text]
  • Extracts of Peanut Skins As a Source of Bioactive Compounds: Methodology and Applications
    applied sciences Review Extracts of Peanut Skins as a Source of Bioactive Compounds: Methodology and Applications Lisa L. Dean Food Science and Market Quality and Handling Research Unit, USDA, ARS, SEA, Raleigh, NC 27695-7624, USA; [email protected]; Tel.: +1-919-515-9110 Received: 30 October 2020; Accepted: 26 November 2020; Published: 29 November 2020 Featured Application: Optimized extraction of polyphenols from peanut skins. Abstract: Peanut skins are a waste product of the peanut processing industry with little commercial value. They are also significant sources of the polyphenolic compounds that are noted for their bioactivity. The extraction procedures for these compounds range from simple single solvent extracts to sophisticated separation schemes to isolate and identify the large range of compounds present. To take advantage of the bioactivities attributed to the polyphenols present, a range of products both edible and nonedible containing peanut skin extracts have been developed. This review presents the range of studies to date that are dedicated to extracting these compounds from peanut skins and their various applications. Keywords: peanut skins; peanut testa; peanut processing; polyphenols; procyanidins; agricultural waste; bioactivity; antioxidants 1. Introduction The global production of peanuts is projected to be 47 metric tons for the 2020 crop year [1]. In addition to the edible kernel, the peanut seed consists of the woody outer shell and a paper-like substance that surrounds the kernel itself known as the testa or skin. For most peanut products, the skin is removed and discarded [2]. The skin removal is done by a process known as blanching, which subjects the shelled raw peanut kernels to mild dry heat treatment and mechanical abrasion.
    [Show full text]