DOCSLIB.ORG

Structure–Activity Relationships of Flavonoids for Vascular Relaxation In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Structure–Activity Relationships of Flavonoids for Vascular Relaxation In PHYTOCHEMISTRY Phytochemistry 68 (2007) 1179–1188 www.elsevier.com/locate/phytochem Structure–activity relationships of flavonoids for vascular relaxation in porcine coronary artery Y.C. Xu a, S.W.S. Leung a, D.K.Y. Yeung a, L.H. Hu b, G.H. Chen b, C.M. Che b,c, R.Y.K. Man a,c,* a Department of Pharmacology, Faculty of Medicine, The University of Hong Kong Pokfulam Road, Hong Kong SAR, PR China b Department of Chemistry, Faculty of Science, The University of Hong Kong Pokfulam Road, Hong Kong SAR, PR China c Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong Pokfulam Road, Hong Kong SAR, PR China Received 11 July 2006; received in revised form 20 November 2006 Available online 28 March 2007 Abstract Flavonoids are polyphenolic compounds that are widespread in the plant kingdom, and structure–activity relationships (SAR) for vascular relaxation effects were examined for 17 of them using porcine coronary arteries. Density functional theory was employed to calculate the chemical parameters of these compounds. The order of potency for vascular relaxation was as follows: flavones (apigenin and luteolin) P flavonols (kaempferol and quercetin) > isoflavones (genistein and daidzein) > flavanon(ol)es (naringenin) > chalcones (phloretin) > anthocyanidins (pelargonidin) > flavan(ol)es ((+)-catechin and (À)-epicatechin). SAR analysis revealed that for good relax- ation activity, the 5-OH, 7-OH, 40-OH, C2@C3 and C4@O functionalities were essential. Comparison of rutin with quercetin, genistin with genistein, and puerarin with daidzein demonstrated that the presence of a glycosylation group greatly reduced relaxation effect. Total energy and molecular volume were also predictive of their relaxation activities. Our findings indicated that the most effective relax- ing agents are apigenin, luteolin, kaempferol and genistein. These flavonoids possess the key chemical structures demonstrated in our SAR analysis. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Flavonoid; Structure–activity relationship; Chemical parameter; Relaxation activity; Porcine coronary artery 1. Introduction focused on their cardiovascular effects (Vitor et al., 2004; Stocker and O’Halloran, 2004). Epidemiological reports Flavonoids are polyphenolic compounds that are wide- have demonstrated that people can have lower incidence spread in the plant kingdom, and they are important of heart diseases if they have a high dietary intake of flavo- components of many traditional Chinese medicine and noids (Knekt et al., 2002; Jenkins et al., 2003) and this may phyto-medicine. They have diverse pharmacological effects, help explain the lower mortality of coronary heart diseases such as anticancer, antioxidant, anti-aging, and antibacterial in some Asian countries (Lock et al., 1988). Furthermore, properties (Terao et al., 1994; Bos et al., 1996; Guo et al., other studies have demonstrated that some flavonoids pro- 1999; Meng and Wang, 2001). Recently many studies have duced concentration-dependent relaxation responses in contracted arterial rings (Guerrero et al., 2002; Fusi et al., 2003). These relaxations are in part mediated by stimulation of nitric oxide release from the endothelium * Corresponding author. Present address: 2/F Laboratory Block, Faculty of Medicine Complex, 21 Sassoon Road, Hong Kong SAR, (Kim et al., 2000; Mishra et al., 2000; Zhang et al., China. Tel.: +852 2819 9250; fax: +852 2817 0859. 2002). However, the majority of the relaxation is attributed E-mail address: [email protected] (R.Y.K. Man). to direct action of the flavonoids on the vascular smooth 0031-9422/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2007.02.013 1180 Y.C. Xu et al. / Phytochemistry 68 (2007) 1179–1188 muscle (Mishra et al., 2000; Zhang et al., 2002; Ajar et al., 1995; Vaya and Tamir, 2004). Certain chemical parameters 2003). may be responsible for their molecular interactions (Cam- Since different flavonoids have different relaxation argo et al., 2002). Therefore, SAR studies using quantum effects, the structure–activity relationships (SAR) of flavo- chemical parameters have become important in qualitative noids have become the subject of many investigations (Hii- and quantitative analyses of three-dimensional molecular pakka et al., 2002; Taubert et al., 2002; Chen et al., 2003; interactions (Dewar et al., 1985; Souza et al., 2003). How- van Zanden et al., 2004). For an understanding of the ever, few investigations have examined the relationships three-dimensional microscopic interaction and binding between chemical parameters and vascular relaxation of between a ligand and a receptor, detailed analysis in SAR flavonoids. The present study focuses on SAR analysis of is important in drug design and synthesis (Costa et al., 17 natural compounds (1–17) using structural parameters OH OH OH HO HO O O (Z) (Z) OH O OH O Apigenin (1) Luteolin (2) OH OH OH HO O HO O (E) (E) OH OH OH O OH O Kaempferol (3) Quercetin (4) OH OH HO O OH (E) OH OH HO O O OH OH O OH HO O CH2 (Z) O H3C HO O OH OH OH O HO Myricetin (5) Rutin (6) OH OH OH HO O HO O OH OH O OH O Naringenin (7) Taxifolin (8) Fig. 1. Molecular structures of the 17 flavonoids* studied. *The numbering system for these flavonoids is as follows: Y.C. Xu et al. / Phytochemistry 68 (2007) 1179–1188 1181 OH OH OH OH H HO H O HO O (R) (R) H (S) (R) OH OH H OH OH (+)-Catechin (9) (-)-Epicatechin (10) OH (Z) OH HO + O HO OH (Z) OH OH OH O Phloretin (11) Pelargonidin (12) HOH2C O HO O HO O O HO OH H2O (Z) (Z) OH O OH O OH OH Genistein (13) Genistin (14) HO HO O OH CH2OH HO O HO O (Z) (Z) O O OH OH Puerarin (15) Daidzein (16) HO O (Z) OH3C O OH Glycetein (17) 3' 2' 4' 8 1 B O 2 1' 5' 7 A C 6' 6 3 5 4 Fig. 1 (continued) 1182 Table 1 Names and classes of natural flavonoids in this study, and relaxation properties Number Class Chemical name Compound name % Relation Relaxation effect 30 lM 100 lM 1 Flavones 40,5,7-trihydroxy flavone Apigenin 114.5 ± 3.5* 118.5 ± 3.9* Good 230,40,5,7-tetrahydroxy flavone Luteolin 107.6 ± 2.7* 114.2 ± 2.6* Good 3 Flavonols 3,40,5,7- tetrahydroxy flavone Kaempferol 108.2 ± 2.7* 116.4 ± 2.3* Good 4 3,30,40,5,7- pentahydroxy flavone Quercetin 20.6 ± 3.8 116.7 ± 4.0* Moderate 5 3,30,40,5,50,7- hexahydroxy flavone Myricetin 22.4 ± 3.1 55.8 ± 6.9* Weak 630,40,5,7-tetrahydroxy-3-O-rutinose flavone Rutin 29.7 ± 3.5 73.6 ± 6.9* Weak 7 Flavanon(ol)es 4,5,7- trihydroxy flavanone Naringenin 75.2 ± 4.4* 108.4 ± 1.2* Moderate 8 3,30,40,5,7- pentahydroxy flavanone Taxifolin 45.5 ± 7.0 80.6 ± 4.4* Weak 9 Flavan(ol)es (+)-trans-3,30,40,5,7- pentahydroxy flavane (+)-catechin 31.9 ± 7.9 56.2 ± 7.4* Weak 10 cis-3,30,40,5,7- pentahydroxy flavane (À)-epicatechin 34.0 ± 8.7 66.8 ± 7.6* Weak 11 Chalcones 20,40,60-trihydroxy-3-(4-hydroxyphenyl)propiophenone Phloretin 68.2 ± 6.9* 105.8 ± 1.8* Moderate 12 Anthocyanidins 3,40,5,7- tetrahydroxy flavylium Pelargonidin 54.8 ± 9.5* 87.9 ± 5.3* Moderate Y.C. Xu et al. / Phytochemistry 68 (2007) 1179–1188 13 Isoflavones 3,40,5,7- tetrahydroxy isoflavone Genistein 95.4 ± 3.2* 106.2 ± 3.7* Good 14 3,40,5,7- tetrahydroxy isoflavone 7-glucoside Genistin 24.4 ± 1.1 25.1 ± 2.4 None 15 40,7-dihydroxy-8-b-D-glucose isoflavone Puerarin 25.3 ± 4.8 45.0 ± 5.5* Weak 16 40,7-dihydroxy isoflavone Daidzein 77.3 ± 3.2* 102.9 ± 0.6* Moderate 17 40,7-dihydroxy-6-methoxy isoflavone Glycetein 46.7 ± 4.3* 93.1 ± 1.7* Moderate Data represent mean ± S.E.M. * P < 0.05 vs the relevant solvent control group. at 30 relaxing agents, whereas those with little or no relaxation ( good relaxing agents,almost and 100% this relaxation(the group at maximal includes 30 (the relaxation). apigenin concentration to The achieveinto 50% three flavonoids relaxation) categories andvasorelaxation, efficacy that taken it into induce account isgroups of possible ( their to potency 100 classify these flavonoids maximum concentration tested, i.e.30 100 noids inducing 50% relaxation at concentration around genistin ( tracted with U46619 (30endothelium-intact nM), porcine all coronary tested arterycontraction that flavonoids were except in con- thewere presence expressed of asbiological the evaluation a tested of percentage flavonoids compound.Table examined relaxation In 1 in of thiscompound the study name initial ofstructures are the showed 17and in flavonoids without are anvasorelaxant intact presented activities endothelium, in inent and porcine their subgroups coronary molecular of arteries flavonoids with weresugar attached. investigated forsubstituent, their the degreeglycosylated of substitutents, unsaturation the androne position and the of differ the types fromFlavonoids benzenoide of one are based another on in themethod terms structure of of is a hydroxyl phenylbenzopy- understood. hampered or The by investigationnism(s) their of for flavonoids vast by theiret structural the al., action diversity. SAR 2002; andvascular Jenkins protection SAR et ( al., haveamount 2003 of not interest with been regard to fully their potential in cardio- 2.1. In vitro vascular relaxation activity 2. Results and discussion investigated. effects of flavonoids incalculated porcine coronary by arteries were density also functional theory. The vascular consistent with thethe findings type of andegories species are of shown thecurves in blood of vessels, some representative our flavonoidsweak results in these are vasodilators three cat- ( lium, flavonoids also induced significant relaxation.
Load more

Recommended publications
  • Cytoprotective Effect of Liposomal Puerarin on High Glucose-Induced Injury in Rat Mesangial Cells
    antioxidants Article Cytoprotective Effect of Liposomal Puerarin on High Glucose-Induced Injury in Rat Mesangial Cells Lassina Barro 1 , Jui-Ting Hsiao 1, Chu-Yin Chen 1, Yu-Lung Chang 1,2 and Ming-Fa Hsieh 1,* 1 Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan 320, Taiwan; [email protected] (L.B.); [email protected] (J.-T.H.); [email protected] (C.-Y.C.); [email protected] (Y.-L.C.) 2 Department of Urology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 320, Taiwan * Correspondence: [email protected]; Tel.: +886-3265-4550 Abstract: In diabetic patients, high glucose and high oxidative states activate gene expression of transforming growth factor beta (TGF-β) and further translocate Smad proteins into the nucleus of renal cells. This signal pathway is characterized as the onset of diabetic nephropathy. Puerarin is an active ingredient extracted from Pueraria lobata as an anti-hyperglycemic and anti-oxidative agent. However, the poor oral availability and aqueous solubility limit its pharmaceutical applications. The present paper reports the liposomal puerarin and its protective effect on high glucose-injured rat mesangial cells (RMCs). The purity of puerarin extracted from the root of plant Pueraria lobata was 83.4% as determined by the high-performance liquid chromatography (HPLC) method. The liposomal puerarin was fabricated by membrane hydration followed by ultrasound dispersion and membrane extrusion (pore size of 200 nm). The fabricated liposomes were examined for the loading efficiency and contents of puerarin, the particle characterizations, the radical scavenge and the Citation: Barro, L.; Hsiao, J.-T.; Chen, protective effect in rat mesangial cells, respectively.
    [Show full text]
  • Flavonoid Glucodiversification with Engineered Sucrose-Active Enzymes Yannick Malbert
    Flavonoid glucodiversification with engineered sucrose-active enzymes Yannick Malbert To cite this version: Yannick Malbert. Flavonoid glucodiversification with engineered sucrose-active enzymes. Biotechnol- ogy. INSA de Toulouse, 2014. English. NNT : 2014ISAT0038. tel-01219406 HAL Id: tel-01219406 https://tel.archives-ouvertes.fr/tel-01219406 Submitted on 22 Oct 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Last name: MALBERT First name: Yannick Title: Flavonoid glucodiversification with engineered sucrose-active enzymes Speciality: Ecological, Veterinary, Agronomic Sciences and Bioengineering, Field: Enzymatic and microbial engineering. Year: 2014 Number of pages: 257 Flavonoid glycosides are natural plant secondary metabolites exhibiting many physicochemical and biological properties. Glycosylation usually improves flavonoid solubility but access to flavonoid glycosides is limited by their low production levels in plants. In this thesis work, the focus was placed on the development of new glucodiversification routes of natural flavonoids by taking advantage of protein engineering. Two biochemically and structurally characterized recombinant transglucosylases, the amylosucrase from Neisseria polysaccharea and the α-(1→2) branching sucrase, a truncated form of the dextransucrase from L. Mesenteroides NRRL B-1299, were selected to attempt glucosylation of different flavonoids, synthesize new α-glucoside derivatives with original patterns of glucosylation and hopefully improved their water-solubility.
    [Show full text]
  • Contrasting Effects of Puerarin and Daidzin on Glucose Homeostasis in Mice
    8760 J. Agric. Food Chem. 2005, 53, 8760−8767 Contrasting Effects of Puerarin and Daidzin on Glucose Homeostasis in Mice ELIAS MEEZAN,† ELISABETH M. MEEZAN,† KENNETH JONES,† RAY MOORE,‡ | STEPHEN BARNES,†,‡,§, AND JEEVAN K. PRASAIN*,†,§ Department of Pharmacology & Toxicology, Comprehensive Cancer Center Mass Spectrometry Shared Facility, and Purdue-UAB Botanicals Center for Age-Related Diseases, and UAB Center for Nutrient-Gene Interaction in Cancer Prevention, University of Alabama at Birmingham, Birmingham, Alabama 35294 Puerarin and daidzin are the major isoflavone glucosides found in kudzu dietary supplements. In this study, we demonstrated that puerarin significantly improves glucose tolerance in C57BL/6J-ob/ob mice, an animal model of type 2 diabetes mellitus, blunting the rise in blood glucose levels after i.p. administration of glucose. In contrast, daidzin, the O-glucoside, had a significant but opposite effect, impairing glucose tolerance as compared to saline-treated controls. When they were administered i.p. with 14C-glucose to C57BL/6J lean mice, puerarin inhibited glucose uptake into tissues and incorporation into glycogen, while daidzin stimulated glucose uptake, showing an opposite effect to puerarin. Puerarin also antagonized the stimulatory effect of decyl-â-D-thiomaltoside, an artificial primer of glycogen synthesis, which increases 14C-glucose uptake and incorporation into glycogen in mouse liver and heart. A liquid chromatography-tandem mass spectrometry procedure was used to investigate the metabolism and bioavailability of puerarin and daidzin. The blood puerarin concentra- tion-time curve by i.p. and oral administration indicated that puerarin was four times more bioavailable via i.p. injection than via the oral route of administration.
    [Show full text]
  • MS/MS Analysis of Polyphenols
    Purdue-UAB Botanicals Center for Age-Related Disease MS/MSMS/MS analysisanalysis ofof PolyphenolsPolyphenols Jeevan Prasain Ph.D. Pharmacology & Toxicology UAB Polyphenols Phenolic acids Flavonoids Stilbenes Lignans and derivatives OH HO CH2O OH HO CH2O HO Flavanols Flavonols Isoflavones OH Caffeic acid OH OH O OH HO Resveratrol Enterodiol OH O (Stilbene) (Lignan) HO O OH OH O OH OH OH Genistein (Isoflavone) OH EGC (Flavanol) HO O OH OH OH O Quercetin (Flavonol) LC-MS Profile of the methanolic extract of KDS Column: C8 Aquapore; 7µm, 100 x 4.6 mm i.d. Solvent: CH3CN:H2O (10-40%, run time 30 min) m/z 415 puerarin 100 m/z 341 m/z 415 m/z 253 DZN DZ’N 75 m/z 547 ) % ( m/z 283 y m/z 445 50 m/z 267 Formononetin m/z 445 25 m/z 431 m/z 431 G’N Relative Intensit 0 0 4 8 12 16 Time (min) WhatWhat isis tandemtandem massmass spectrometry?spectrometry? The ability to induce fragmentation and perform successive mass spectrometry experiments (MS/MS) on those fragments. In MS/MS mode, product ion, precursor ion and constant neutral loss scans are performed. Multiple reaction monitoring (MRM) is useful technique for quantitation. How does it work? Tandem in space means having two mass spectrometers in series. It uses two stages of mass analysis, one to pre-select an ion and the Second to analyze fragments induced, for instance, by collision with An inert gas like argon or helium. This dual analysis can be dual in Space, or dual in time.
    [Show full text]
  • Isoflavones As Modulators of Adenosine Monophosphate
    Appl Biol Chem (2016) 59(2):217–225 Online ISSN 2468-0842 DOI 10.1007/s13765-016-0149-8 Print ISSN 2468-0834 ARTICLE Isoflavones as modulators of adenosine monophosphate-activated protein kinase Hyeryoung Jung1 . Seunghyun Ahn1 . Beum Soo Kim1 . Soon Young Shin2 . Young Han Lee2 . Yoongho Lim1 Received: 2 November 2015 / Accepted: 9 November 2015 / Published online: 29 January 2016 Ó The Korean Society for Applied Biological Chemistry 2016 Abstract Adenosine monophosphate-activated protein Introduction kinase (AMPK) is expressed in all eukaryotic cells and can therefore be found in vertebrates, invertebrates, and plants. Adenosine monophosphate (AMP)-activated protein kinase Since AMPK participates in the regulation of homeostasis (AMPK) is expressed in all eukaryotic cells and is present on various levels, small compounds that can modulate in vertebrates, invertebrates, and plants (Ghillebert et al. AMPK activity could be valuable research tools. Several 2011). It was first identified in 1988, and mammalian flavonoids can modulate AMPK. Here we investigated the AMPK was purified and sequenced in 1994 (Munday et al. modulatory effect of 37 isoflavones on AMPK activity 1988; Mitchelhill et al. 1994). Although AMPK was dis- using an in vitro kinase assay. Because the relationship covered only recently, a large body of knowledge exists on between the structural properties of flavonoids and their its function because it plays various roles in the regulation modulatory activities has not been elucidated yet, we used of homeostasis. AMPK regulates carbohydrate metabolism, comparative molecular field analysis to derive the struc- including glycolysis, glycogen metabolism, and glucose tural conditions for modulation of AMPK activity. The uptake, sensing, and production.
    [Show full text]
  • Potential Herb–Drug Interactions in the Management of Age-Related Cognitive Dysfunction
    pharmaceutics Review Potential Herb–Drug Interactions in the Management of Age-Related Cognitive Dysfunction Maria D. Auxtero 1, Susana Chalante 1,Mário R. Abade 1 , Rui Jorge 1,2,3 and Ana I. Fernandes 1,* 1 CiiEM, Interdisciplinary Research Centre Egas Moniz, Instituto Universitário Egas Moniz, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal; [email protected] (M.D.A.); [email protected] (S.C.); [email protected] (M.R.A.); [email protected] (R.J.) 2 Polytechnic Institute of Santarém, School of Agriculture, Quinta do Galinheiro, 2001-904 Santarém, Portugal 3 CIEQV, Life Quality Research Centre, IPSantarém/IPLeiria, Avenida Dr. Mário Soares, 110, 2040-413 Rio Maior, Portugal * Correspondence: [email protected]; Tel.: +35-12-1294-6823 Abstract: Late-life mild cognitive impairment and dementia represent a significant burden on health- care systems and a unique challenge to medicine due to the currently limited treatment options. Plant phytochemicals have been considered in alternative, or complementary, prevention and treat- ment strategies. Herbals are consumed as such, or as food supplements, whose consumption has recently increased. However, these products are not exempt from adverse effects and pharmaco- logical interactions, presenting a special risk in aged, polymedicated individuals. Understanding pharmacokinetic and pharmacodynamic interactions is warranted to avoid undesirable adverse drug reactions, which may result in unwanted side-effects or therapeutic failure. The present study reviews the potential interactions between selected bioactive compounds (170) used by seniors for cognitive enhancement and representative drugs of 10 pharmacotherapeutic classes commonly prescribed to the middle-aged adults, often multimorbid and polymedicated, to anticipate and prevent risks arising from their co-administration.
    [Show full text]
  • The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action
    nutrients Article The Neuroprotective Effects of Phenolic Acids: Molecular Mechanism of Action Dominik Szwajgier, Kamila Borowiec * and Katarzyna Pustelniak Department of Biotechnology, Human Nutrition and the Science of Food Commodities, University of Life Sciences in Lublin, Lublin 20704, Poland; [email protected] (D.S.); [email protected] (K.P.) * Correspondence: [email protected]; Tel./Fax: +48-81-462-33-53 Received: 23 March 2017; Accepted: 4 May 2017; Published: 10 May 2017 Abstract: The neuroprotective role of phenolic acids from food has previously been reported by many authors. In this review, the role of phenolic acids in ameliorating depression, ischemia/reperfusion injury, neuroinflammation, apoptosis, glutamate-induced toxicity, epilepsy, imbalance after traumatic brain injury, hyperinsulinemia-induced memory impairment, hearing and vision disturbances, Parkinson’s disease, Huntington’s disease, anti-amyotrophic lateral sclerosis, Chagas disease and other less distributed diseases is discussed. This review covers the in vitro, ex vivo and in vivo studies concerning the prevention and treatment of neurological disorders (on the biochemical and gene expression levels) by phenolic acids. Keywords: cinnamic acids; benzoic acids; polyphenols; neuroprotection; neuroinflammation; central nervous system; neuron; glial cell; neurological disorder 1. Introduction Phenolic acids are one of the main classes of polyphenols. They are abundantly present in foods such as berries [1], nuts [2], coffee and tea [3] and whole grains [4]. Importantly, a recent meta-analysis showed that phenolic acid-rich foods decrease the risk of depression [5,6]. Figure1 presents the chemical structures of phenolic acids discussed in this work. Previously, authors focused mainly on the antioxidant and antiradical activities of phenolic acids.
    [Show full text]
  • Epigallocatechin Gallate and Quercetin on the Activity and Structure of Α-Amylase
    Su & Tang Tropical Journal of Pharmaceutical Research March 2019; 18 (3): 585-590 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v18i3.20 Original Research Article Effects of (-)-epigallocatechin gallate and quercetin on the activity and structure of α-amylase Jianhui Su, Zhe Tang* School of Marine and Bioengineering, Yancheng Institute of Technology, Yancheng 224051, PR China *For correspondence: Email: [email protected] Sent for review: 4 September 2018 Revised accepted: 18 February 2019 Abstract Purpose: To investigate the effects of (-)-epigallocatechin gallate (EGCG) and quercetin on the activity and structure of α-amylase. Methods: The inhibitory effects of 7 functional factors were compared by measuring half maximal inhibitory concentration (IC50) values. Lineweaver-Burk plots were used to determine the type of inhibition exerted by EGCG and quercetin against α-amylase. The effect of EGCG and quercetin on the conformation of α-amylase was investigated using fluorescence spectroscopy. Results: Quercetin and EGCG inhibited α-amylase with IC50 values of 1.36 and 0.31 mg/mL, respectively, which were much lower than the IC50 values of the other compounds (puerarin, paeonol, konjac glucomannan and polygonatum odoratum polysaccharide). The Lineweaver−Burk plots indicated that EGCG and quercetin inhibited α-amylase competitively, with ki values of 0.23 and 1.28 mg/mL, respectively. Fluorescence spectroscopy revealed that treatment with EGCG and quercetin led to formation of a loosely-structured hydrophobic hydration layer. Conclusion: This study has unraveled the mechanism underlying the inhibition of α-amylase activity by EGCG and quercetin in vitro.
    [Show full text]
  • Puerarin Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting Autophagy Via the Akt Signaling Pathway
    MOLECULAR MEDICINE REPORTS 15: 3747-3754, 2017 Puerarin attenuates myocardial hypoxia/reoxygenation injury by inhibiting autophagy via the Akt signaling pathway HUIXIONG TANG1*, XUDONG SONG1*, YUANNA LING1, XIANBAO WANG1, PINGZHEN YANG1, TAO LUO2 and AIHUA CHEN1 1Department of Cardiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China; 2Division of Cardiology, Department of Medicine, University of California Irvine Medical Center, Orange, CA 92868, USA Received December 22, 2015; Accepted February 1, 2017 DOI: 10.3892/mmr.2017.6424 Abstract. Puerarin (Pur), which is the major bioactive ingre- may attenuate myocardial H/R injury by inhibiting autophagy dient extracted from the root of Pueraria lobata (Willd.) via the Akt signaling pathway. Ohwi, has been demonstrated to relieve myocardial ischemia/ reperfusion (I/R) injury. Macroautophagy, or autophagy, is an Introduction evolutionarily conserved cellular catabolic mechanism that is involved in myocardial I/R injury. The present study evaluated Puerarin (Pur), which is the major bioactive ingredient the involvement of autophagy in the protective mechanisms extracted from the root of Pueraria lobata (Willd.) Ohwi, has of Pur during myocardial hypoxia/reoxygenation (H/R). The been widely used in the treatment of cardiovascular diseases, results revealed that Pur and 3-methyladenine pretreatment cerebrovascular disorders and diabetes in China (1). Pur has been exerted a cardioprotective effect against H/R-induced cell demonstrated to exert the following protective effects against viability loss. Pur also decreased the ratio of light chain 3 (LC3) myocardial ischemia/reperfusion (I/R) injury: Amelioration -II/LC3-I and the degradation of p62 during H/R, which was of oxygen consumption, restriction of the infarct area and accompanied by an increased level of phosphorylated-protein improvement of diastolic function (2,3).
    [Show full text]
  • The Root Extract of Pueraria Lobata and Its Main Compound, Puerarin, Prevent Obesity by Increasing the Energy Metabolism in Skeletal Muscle
    nutrients Article The Root Extract of Pueraria lobata and Its Main Compound, Puerarin, Prevent Obesity by Increasing the Energy Metabolism in Skeletal Muscle Hyo Won Jung 1,2, An Na Kang 1,2, Seok Yong Kang 1,2, Yong-Ki Park 1,2 and Mi Young Song 2,3,* 1 Department of Herbology, College of Korean medicine, Dongguk University, Dongdaero 123, Gyeongju-si 38066, Korea; [email protected] (H.W.J.); [email protected] (A.N.K.); [email protected] (S.Y.K.); [email protected] (Y.-K.P.) 2 Korean Medicine R&D Center, College of Korean medicine, Dongguk University, Dongdaero 123, Gyeongju-si 38066, Korea 3 Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University, Dongdaero 123, Gyeongju-si 38066, Korea * Correspondence: [email protected]; Tel.: +82-547-701-264 Received: 5 November 2016; Accepted: 29 December 2016; Published: 4 January 2017 Abstract: Radix Pueraria lobata (RP) has been reported to prevent obesity and improve glucose metabolism; however, the mechanism responsible for these effects has not been elucidated. The mechanism underlying anti-obesity effect of RP was investigated in high-fat diet (HFD) induced obese mice and skeletal muscle cells (C2C12). Five-week-old C5BL/6 mice were fed a HFD containing or not containing RP (100 or 300 mg/kg) or metformin (250 mg/kg) for 16 weeks. RP reduced body weight gain, lipid accumulation in liver, and adipocyte and blood lipid levels. In addition, RP dose-dependently improved hyperglycemia, insulinemia, and glucose tolerance, and prevented the skeletal muscle atrophy induced by HFD.
    [Show full text]
  • Evaluation of Anti-Melanogenesis Activity of Enriched Pueraria Lobata Stem Extracts and Characterization of Its Phytochemical Components Using HPLC–PDA–ESI–MS/MS
    International Journal of Molecular Sciences Article Evaluation of Anti-Melanogenesis Activity of Enriched Pueraria lobata Stem Extracts and Characterization of Its Phytochemical Components Using HPLC–PDA–ESI–MS/MS Dan Gao 1,† , Jin Hyeok Kim 1,† , Cheong Taek Kim 2, Won Seok Jeong 2, Hyung Min Kim 1 , Jaehoon Sim 1,* and Jong Seong Kang 1,* 1 College of Pharmacy, Chungnam National University, Daejeon 34134, Korea; [email protected] (D.G.); [email protected] (J.H.K.); [email protected] (H.M.K.) 2 RNS Inc., Daejeon 34014, Korea; [email protected] (C.T.K.); [email protected] (W.S.J.) * Correspondence: [email protected] (J.S.); [email protected] (J.S.K.); Tel.: +82-42-821-5938 (J.S.); +82-42-821-5928 (J.S.K.) † Those authors contribute equally. Abstract: The root of Pueraria lobata (Willd.) is a widely used herbal medicine worldwide, whereas the stem of the plant is discarded or used as feed for livestock. To reuse and exploit the stem of P. lobata as a resource, we investigated its potential as a skin-whitening agent. We found that the developed, enriched P. lobata stem (PLS) extract significantly inhibited melanin production in Citation: Gao, D.; Kim, J.H.; Kim, the 3-isobutyl-1-methylxanthine-induced B16/F10 cells at a concentration of 50 µg/mL. To further C.T.; Jeong, W.S.; Kim, H.M.; Sim, J.; confirm the mechanism of the antimelanogenic effect of the enriched PLS extracts, we examined Kang, J.S. Evaluation of the mRNA expression of tyrosinase, which was suppressed by the extracts.
    [Show full text]
  • Comparison Among Activities and Isoflavonoids from Pueraria Thunbergiana Aerial Parts and Root
    Article Comparison among Activities and Isoflavonoids from Pueraria thunbergiana Aerial Parts and Root Eunjung Son 1, Jong-Moon Yoon 2, Bong-Jeun An 2, Yun Mi Lee 1, Jimin Cha 3, Gyeong-Yup Chi 2,*,† and Dong-Seon Kim 1,*,† 1 Herbal Medicine Research Division, Korea Institute of Oriental Medicine,1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea; [email protected] (E.S.); [email protected] (Y.M.L.) 2 Division of Bio-Technology and Convergence, Daegu Haany University, 285-10 Eobongji-gil, Gyeongsan, Gyeongsangbuk-do 38578, Korea; [email protected] (J.-M.Y.); [email protected] (B.-J.A.) 3 Department of Microbiology, Faculty of Natural Science, Dankook University, Cheonan, Chungnam 31116, Korea; [email protected] * Correspondence: [email protected] (G.-Y.C.); [email protected] (D.-S.K.); Tel.: +82-53-819-7741 (G.-Y.C.); +82-42-868-9676 (D.-S.K.) † Dong-Seon Kim and Gyeong-Yup Chi contributed equally to this work. Received: 7 February 2019; Accepted: 25 February 2019; Published: 5 March 2019 Abstract: Kudzu (Pueraria thunbergiana Benth.) has long been used as a food and medicine for many centuries. The root is the most commonly used portion of the plant, but the aerial parts are occasionally used as well. In this study, we investigated the constituent compounds and biological activities of the aerial parts, leaves, stems, and sprouts, and compared their constituents and activities with those of roots. Leaf extract showed a significantly higher TPC level at 59 ± 1.6 mg/g and lower free radical scavenging (FRS) values under 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and NO inhibition at 437 ± 11, 121 ± 6.6 μg/mL and 107 ± 4.9 μg/mL, respectively, than those of sprout, stem, and root extract.
    [Show full text]