DOCSLIB.ORG

Structurally Diverse Bioflavonoids As Potential Source of Antimalarial Lead Molecules

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Structurally Diverse Bioflavonoids As Potential Source of Antimalarial Lead Molecules STRUCTURALLY DIVERSE BIOFLAVONOIDS AS POTENTIAL SOURCE OF ANTIMALARIAL LEAD MOLECULES Dipak Chetia* and Mithun Rudrapal Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh-786 004, Assam E-mail: [email protected] Abstract: In this article, a review on bioactive flavonoids that are abundant in medicinal and functional food (dietary) plants has been made, with special reference to antimalarial flavonoid molecules. Flavonoids have been found to exist in plants/plant medicines with a wide structural diversity consisting of numerous polyphenolic compounds and having well defined molecular target specificity. These phytoconstituents may serve as important natural lead molecules for their development as potent antimalarial therapeutic agents. Keywords: Malaria, drug resistance, bioflavonoids, pharmacophoric scaffolds, antimalarial drugs 1. INTRODUCTION Malaria is a serious infectious disease that malaria-related deaths worldwide. Moreover, P. affects people of all ages, particularly in tropical falciparum strains produce rapid as well as varying and subtropical regions of the world. According to degree of resistance against currently available the World Health Organization (WHO), antimalarial drugs, which has become a major approximately 40% of the world population live in clinical issue in the malaria chemotherapy [1-6]. malaria endemic areas, with 300-500 million Plant-based medicines have been playing clinical cases and 1.5-2.7 million deaths per year an important role in the treatment of malaria since globally. In the South East Asian region, out of ancient times. Malaria treatment in the modern about 1.4 billion people living in 11 countries, 1.2 therapeutic form started with the discovery of billion (85.7%) are exposed to the risk of malaria. quinine (QN) from cinchona bark. The quinoline- Of the 2.5 million reported cases in the South East based synthetic antimalarial drugs (Figure I) such Asia, India alone contributes about 70% of the total as chloroquine (CQ) were successfully used in the cases. Human malaria is caused by five species of treatment of malaria for a long time [2, 3, 7]. Plasmodium, namely, P. falciparum, P. vivax, P. However, with the pace of time their clinical uses Ovale, P. malariae and P. knowlesi. Plasmodium have become limited because of the development falciparum is the most widespread and extremely of resistant strains of malarial parasites, especially dangerous species, which causes potentially fatal of P. falciparum. malaria such as cerebral malaria, and most of the H OH H N N N HN HN HO H3CO N Cl N Cl N Chloroquine (CQ) Amodiaquine (AQ) Quinine (QN) Fig. I: Quinoline-based antimalarial drugs Artemisinin (ART), isolated from the then successfully incorporated as potent drugs in plant, Artemisia annua was later introduced, and its the treatment of malaria in resistant cases [7, 8]. several semi-synthetic derivatives (Figure II) were 64 CH3 CH H 3 CH3 H H O O H CH3 H CH O Reduction O Derivatization 3 O H CH3 O O O O O H C O 3 O H3C H C O 3 RO OH Artemisinin Dihydroartemisinin R=Me, Artemether R=Et, Arteether R=CO(CH2)2COONa, Sodium artesaunate R=CH2 (p-C6H4)COONa, Sodium artelinate Fig. II: Artemisinin (ART) and its semi-synthetic derivatives Currently, artemisinin-based combination xanthones, limonoids, steroids etc. and they possess therapies (ACTs) are recommended by the WHO a diverse range of activity profile in terms of health for the treatment of multidrug-resistant P. implications. Among all these, flavonoids have falciparum malaria. Some examples of ACTs are recently gained significant interest among artemether plus lumefantrine, artesunate plus medicinal chemists because of their promising mefloquine (MQ), and artesunate plus chemopreventive ∕chemoprotective potentials in pyronaridine. But, the ACTs are costlier relative to inflammatory disorders, cardiovascular diseases, CQ and QN, and also, resistance to ART and MQ- diabetes, neurodegenerative disorders, cancer, ART against P. falciparum has begun to emerge in bacterial infections and malaria [11, 12]. In tune Southeast Asia. Therefore, the treatment of malaria with the above facts, researchers have investigated has increasingly become a challenging task because many plant species for their antimalarial activities of the emergence of the resistant strains of malaria and have reported the bioactive principles including parasites, which has created an urgent need to flavonoids responsible for antimalarial develop new and therapeutically efficacious effectiveness. A number of polyphenolic flavonoids antimalarial agents [8-10]. that are abundant in dietary and medicinal plants However, in order to resolve the above have been identified to have good antimalarial challenging issue, the discovery of newer effectiveness both in-vitro and in-vivo [13]. In this antimalarial drugs from plants and/or plant-based review, plant derived flavonoids which have been traditional medicines is considered to be the most identified to possess antimalarial potential, their reliable alternative approach as nature always chemistry and structural diversity, and basis of their serves as the richest source of chemicals with a bioactivity are described. Flavonoid compounds wide range of structural- and bio- diversity. These with their pharmacophoric structural scaffolds may chemical compounds are basically secondary therefore be potential lead molecules for the metabolites of plant origin belonging to several development of flavonoid-based antimalarial drugs important phytochemical classes such as against the resistant strains of the malaria parasites. terpenoids, alkaloids, flavonoids, coumarins, 2. BIOFLAVONOIDS Flavonoids comprise of a large groups of products, so called phenylpropanoids. More aromatic organic compounds of around 10,000 precisely, the molecular framework of flavonoids structures that are ubiquitously distributed in the consists of a C6-C3-C6 unit i.e., flavonoid plant kingdom. In fact, these compounds are (phenylbenzopyrone) skeleton in which the parent secondary plant metabolites biosynthesized in C6-C3 unit is present as chromone (benzo-훾-pyrone) plants as metabolic hybrids through a combination nucleus (Figure III). The term flavonoid was of the shikimate-derived phenylpropanoid (-->C6- derived from the Latin word flavus meaning C3) pathway and the acetate∕mevalonate polyketide yellow, and the prefix ‘bio’ denotes their biological (-->C6) pathway. They therefore possess a carbon origin as well as their manifested biological skeleton of phenylpropanoid (C6-C3 unit), and significances (including pharmacological effects) hence constitute an important class of natural on other organisms [14-16]. 65 O O O C6-C3 C6-C3 C6-C3-C6 Phenylpropanoid Chromone Flavonoid Fig. III: Parent structures of flavonoids 2.1 Chemistry The chemical structure of flavonoids are are often hydroxylated in positions 3, 5, 6, 7, 3′, 4′, based on the flavonoid (C6-C3-C6) molecular and 5′. The structural skeletons of various types of framework which is a fifteen-carbon skeleton flavonoids are represented in the Figure IV [14-18]. consisting of two benzene rings (A ring and B ring) According to the oxidation state of the interconnected by a three carbon heterocyclic pyran central pyran ring, they can be broadly classified ring (C ring). The chroman ring (C ring) is into: (i) Flavonoids: These are ketone compounds connected to the second aromatic ring (ring B, that include anthoxanthins (flavones and flavonols), benzenoid substituent) at the C-2 (flavone), C-3 isoflavones and neoflavones. The skeletal (e.g., isoflavone) or C-4 (neoflavone) positions. structures of this class of compounds are based Sometimes, in place of six-membered heterocyclic upon flavone backbone. (ii) Flavanoids: These are pyran ring (ring C) an acyclic moiety (chalcone) or mostly non ketone compounds (except flavanols) a five membered heterocyclic furan ring (aurone) is having flavan backbone that include flavanones, found. Six-membered ring condensed with the flavanols, and flavanonols. Flavonoids differ from benzene ring is either a 훾-pyrone (flavones, flavanoids mainly by a C2–C3 double bond. flavonols and isoflavones) or its dihydroderivatives Individual bioactive compounds within a class (flavanones and flavanols). Flavonoids are differ primarily in the pattern of hydroxyl generally hydroxylated phenolic substances and substitution of the A and B rings [16, 17]. therefore, referred to as plant polyphenols. They 3' 2' 4' 8 1' O1 5' 7 2 6' 6 3 5 4 Flavonoid (Flavanoid) skeleton C6-C3-C6 O O O O O OH O O O O Chalcone Aurone Flavone Flavonol Isoflavone O O O O O O OH OH O O Neoflavone Flavan Flavanol Flavanone Flavanonol O O OH OH OH Leucoanthocyanidin Anthocyanidin Fig. IV: Structural skeletons/backbone structures of flavonoids 66 In a much broader sense, the term origin that collectively includes both flavonoids bioflavonoids refers to all compounds of natural and flavanoids. 2.2 Bio- and Structural- diversity Flavonoids are widely distributed in plants as water solubility, lipophilicity and thermostability and occur virtually in all plant parts to impart a flavonoids possess favourable absorption and variety of colours such as yellow, orange, purple, distribution characteristics in human body, which blue etc. to flower petals, fruit peels, vegetables in turn responsible for their better bioavailability and certain grains. Because of their widespread and eventual therapeutic outcomes. Flavonoids are distribution in dietary plants, like fruits and also abundantly found in many medicinal
Load more

Recommended publications
  • Flavonoid Application in Treatment of Oral Cancer-A Review
    European Journal of Molecular & Clinical Medicine ISSN 2515-8260 Volume 07, Issue 01, 2020 FLAVONOID APPLICATION IN TREATMENT OF ORAL CANCER-A REVIEW Sudarsan R1, Lakshmi T2, Anjaneyulu K3 1Undergraduate student, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 77 2Associate Professor, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 77 3 Reader, Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 77 ABSTRACT A wide range of organic compounds that are naturally occurring called flavonoids are primarily found in a large variety of plants. Some of the sources include tea, wine, fruits, grains, nuts and vegetables. There are a number of studies that have proven that a strong association exists between intake of dietary flavonoid and its effects on mortality in the long run. Flavonoids at non-toxic concentrations are known to demonstrate a wide range of therapeutic biological activities in organisms. The contribution of flavonoids in prevention of cancer is an area of great interest in current research. A variety of studies, including in vitro experiments and human trials and even epidemiological investigations, provide compelling evidence which imply that flavonoids’ effects on cancer in terms of chemoprevention and chemotherapy is significant. As the current treatment methods possess a number of drawbacks, the anticancer potential demonstrated by flavonoids makes them a reliable alternative. Various studies have focussed on flavonoids’ anti-cancer potential and its possible application in the treatment of cancer as a chemopreventive agent.
    [Show full text]
  • Effects of Enzymatic and Thermal Processing on Flavones, the Effects of Flavones on Inflammatory Mediators in Vitro, and the Absorption of Flavones in Vivo
    Effects of enzymatic and thermal processing on flavones, the effects of flavones on inflammatory mediators in vitro, and the absorption of flavones in vivo DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Gregory Louis Hostetler Graduate Program in Food Science and Technology The Ohio State University 2011 Dissertation Committee: Steven Schwartz, Advisor Andrea Doseff Erich Grotewold Sheryl Barringer Copyrighted by Gregory Louis Hostetler 2011 Abstract Flavones are abundant in parsley and celery and possess unique anti-inflammatory properties in vitro and in animal models. However, their bioavailability and bioactivity depend in part on the conjugation of sugars and other functional groups to the flavone core. Two studies were conducted to determine the effects of processing on stability and profiles of flavones in celery and parsley, and a third explored the effects of deglycosylation on the anti-inflammatory activity of flavones in vitro and their absorption in vivo. In the first processing study, celery leaves were combined with β-glucosidase-rich food ingredients (almond, flax seed, or chickpea flour) to determine test for enzymatic hydrolysis of flavone apiosylglucosides. Although all of the enzyme-rich ingredients could convert apigenin glucoside to aglycone, none had an effect on apigenin apiosylglucoside. Thermal stability of flavones from celery was also tested by isolating them and heating at 100 °C for up to 5 hours in pH 3, 5, or 7 buffer. Apigenin glucoside was most stable of the flavones tested, with minimal degradation regardless of pH or heating time.
    [Show full text]
  • Identification of Apigenin and Luteolin in Artemisia Annua L. for the Quality
    Phadungrakwittaya et al. Identification of Apigenin and Luteolin inArtemisia annua L. for the Quality Control Rattana Phadungrakwittaya*, Sirikul Chotewuttakorn*, Manoon Piwtong**, Onusa Thamsermsang**, Tawee Laohapand**, Pravit Akarasereenont*,** *Department of Pharmacology, **Center of Applied Thai Traditional Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. ABSTRACT Objective: To identify active compounds and establish the chemical fingerprint ofArtemisia annua L. for the quality control. Methods: Thin-layer chromatography (TLC) conditions were developed to screen for 2 common flavonoids (apigenin and luteolin). Three mobile phases were used to isolate these flavonoids in 80% ethanolic extract of A. annua. Hexane : ethyl acetate : acetic acid (31:14:5, v/v) and toluene : 1,4-dioxane : acetic acid (90:25:4, v/v) were used in normal phase TLC (NP-TLC), and 5.5% formic acid in water : methanol (50:50, v/v) were used in reverse phase TLC (RP-TLC). Chromatograms were visualized under visible light after spraying with Fast Blue B Salt. Apigenin and luteolin bands were checked by comparing their Rf values and UV-Vis absorption spectra with reference markers. Results: Apigenin and luteolin were simultaneously detected with good specificity in RP-TLC condition, while only apigenin was detected in NP-TLC condition. Apigenin band intensity was higher than luteolin band intensity in both conditions. Conclusion: This knowledge can be applied to the development of quality control assessments to ensure product efficacy and consistency. Keywords: Artemisia annua L.; TLC fingerprint; apigenin; luteolin (Siriraj Med J 2019;71: 240-245) INTRODUCTION Thai herbal recipes that are published in The National Artemisia annua L., commonly known as sweet List of Essential Medicines.2 Several previous studies wormwood, is an annual plant in the Asteraceae (Compositae) reported that A.
    [Show full text]
  • The Phytochemistry of Cherokee Aromatic Medicinal Plants
    medicines Review The Phytochemistry of Cherokee Aromatic Medicinal Plants William N. Setzer 1,2 1 Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA; [email protected]; Tel.: +1-256-824-6519 2 Aromatic Plant Research Center, 230 N 1200 E, Suite 102, Lehi, UT 84043, USA Received: 25 October 2018; Accepted: 8 November 2018; Published: 12 November 2018 Abstract: Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers in North America. Methods: The aim of this review was to examine the Cherokee ethnobotanical literature and the published phytochemical investigations on Cherokee medicinal plants and to correlate phytochemical constituents with traditional uses and biological activities. Results: Several Cherokee medicinal plants are still in use today as herbal medicines, including, for example, yarrow (Achillea millefolium), black cohosh (Cimicifuga racemosa), American ginseng (Panax quinquefolius), and blue skullcap (Scutellaria lateriflora). This review presents a summary of the traditional uses, phytochemical constituents, and biological activities of Cherokee aromatic and medicinal plants. Conclusions: The list is not complete, however, as there is still much work needed in phytochemical investigation and pharmacological evaluation of many traditional herbal medicines. Keywords: Cherokee; Native American; traditional herbal medicine; chemical constituents; pharmacology 1. Introduction Natural products have been an important source of medicinal agents throughout history and modern medicine continues to rely on traditional knowledge for treatment of human maladies [1]. Traditional medicines such as Traditional Chinese Medicine [2], Ayurvedic [3], and medicinal plants from Latin America [4] have proven to be rich resources of biologically active compounds and potential new drugs.
    [Show full text]
  • Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times
    Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Traditional Herbal Medicines for Modern Times Each volume in this series provides academia, health sciences, and the herbal medicines industry with in-depth coverage of the herbal remedies for infectious diseases, certain medical conditions, or the plant medicines of a particular country. Series Editor: Dr. Roland Hardman Volume 1 Shengmai San, edited by Kam-Ming Ko Volume 2 Rasayana: Ayurvedic Herbs for Rejuvenation and Longevity, by H.S. Puri Volume 3 Sho-Saiko-To: (Xiao-Chai-Hu-Tang) Scientific Evaluation and Clinical Applications, by Yukio Ogihara and Masaki Aburada Volume 4 Traditional Medicinal Plants and Malaria, edited by Merlin Willcox, Gerard Bodeker, and Philippe Rasoanaivo Volume 5 Juzen-taiho-to (Shi-Quan-Da-Bu-Tang): Scientific Evaluation and Clinical Applications, edited by Haruki Yamada and Ikuo Saiki Volume 6 Traditional Medicines for Modern Times: Antidiabetic Plants, edited by Amala Soumyanath Volume 7 Bupleurum Species: Scientific Evaluation and Clinical Applications, edited by Sheng-Li Pan Traditional Herbal Medicines for Modern Times Herbal Principles in Cosmetics Properties and Mechanisms of Action Bruno Burlando, Luisella Verotta, Laura Cornara, and Elisa Bottini-Massa Cover art design by Carlo Del Vecchio. CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2010 by Taylor and Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-1-4398-1214-3 (Ebook-PDF) This book contains information obtained from authentic and highly regarded sources.
    [Show full text]
  • Systematic Classification of Unknowns Using Fragmentation Spectra
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.17.046672. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license. Classes for the masses: Systematic classification of unknowns using fragmentation spectra Kai Dührkop1, Louis Felix Nothias2, Markus Fleischauer1, Marcus Ludwig1, Martin A. Hoffmann1,3, Juho Rousu4, Pieter C. Dorrestein2, Sebastian Böcker1 1 Chair for Bioinformatics, Friedrich-Schiller-University, Jena, Germany 2 Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, USA 3 International Max Planck Research School “Exploration of Ecological Interactions with Molecular and Chemical Techniques”, Max Planck Institute for Chemical Ecology, Jena, Germany 4 Helsinki institute for Information Technology HIIT, Department of Computer Science, Aalto University, Espoo, Finland ABSTRACT Metabolomics experiments can employ non-targeted tandem mass spectrometry to detect hundreds to thousands of molecules in a biological sample. Structural annotation of molecules is typically carried out by searching their fragmentation spectra in spectral libraries or, recently, in structure databases. Annotations are limited to structures present in the library or database employed, prohibiting a thorough utilization of the experimental data. We present a computational tool for systematic compound class annotation: CANOPUS uses a deep neural network to predict 1,270 compound classes from fragmentation spectra, and explicitly targets compounds where neither spectral nor structural reference data are available. CANOPUS even predicts classes for which no MS/MS training data are available. We demonstrate the broad utility of CANOPUS by investigating the effect of the microbial colonization in the digestive system in mice, and through analysis of the chemodiversity of different Euphorbia plants; both uniquely revealing biological insights at the compound class level.
    [Show full text]
  • Inhibitory Effect of Acacetin, Apigenin, Chrysin and Pinocembrin on Human Cytochrome P450 3A4
    ORIGINAL SCIENTIFIC PAPER Croat. Chem. Acta 2020, 93(1), 33–39 Published online: August 03, 2020 DOI: 10.5562/cca3652 Inhibitory Effect of Acacetin, Apigenin, Chrysin and Pinocembrin on Human Cytochrome P450 3A4 Martin Kondža,1 Hrvoje Rimac,2,3 Željan Maleš,4 Petra Turčić,5 Ivan Ćavar,6 Mirza Bojić2,* 1 University of Mostar, Faculty of Pharmacy, Matice hrvatske bb, 88000 Mostar, Bosnia and Herzegovina 2 University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, A. Kovačića 1, 10000 Zagreb, Croatia 3 South Ural State University, Higher Medical and Biological School, Laboratory of Computational Modeling of Drugs, 454000 Chelyabinsk, Russian Federation 4 University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Botany, Schrottova 39, 10000 Zagreb, Croatia 5 University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmacology, Domagojeva 2, 10000 Zagreb, Croatia 6 University of Mostar, Faculty of Medicine, Kralja Petra Krešimira IV bb, 88000 Mostar, Bosnia and Herzegovina * Corresponding author’s e-mail address: [email protected] RECEIVED: June 26, 2020 REVISED: July 28, 2020 ACCEPTED: July 30, 2020 Abstract: Cytochrome P450 3A4 is the most significant enzyme in metabolism of medications. Flavonoids are common secondary plant metabolites found in fruits and vegetables. Some flavonoids can interact with other drugs by inhibiting cytochrome P450 enzymes. Thus, the objective of this study was to determine inhibition kinetics of cytochrome P450 3A4 by flavonoids: acacetin, apigenin, chrysin and pinocembrin. For this purpose, testosterone was used as marker substrate, and generation of the 6β-hydroxy metabolite was monitored by high performance liquid chromatography coupled with diode array detector.
    [Show full text]
  • Molecular Docking Study on Several Benzoic Acid Derivatives Against SARS-Cov-2
    molecules Article Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2 Amalia Stefaniu *, Lucia Pirvu * , Bujor Albu and Lucia Pintilie National Institute for Chemical-Pharmaceutical Research and Development, 112 Vitan Av., 031299 Bucharest, Romania; [email protected] (B.A.); [email protected] (L.P.) * Correspondence: [email protected] (A.S.); [email protected] (L.P.) Academic Editors: Giovanni Ribaudo and Laura Orian Received: 15 November 2020; Accepted: 1 December 2020; Published: 10 December 2020 Abstract: Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans’ theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski’s and Weber’s rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection. Keywords: SARS-CoV-2; benzoic acid derivatives; gallic acid; molecular docking; reactivity parameters 1. Introduction Severe acute respiratory syndrome coronavirus 2 is an international health matter. Previously unheard research efforts to discover specific treatments are in progress worldwide.
    [Show full text]
  • Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MA
    Int. J. Biol. Sci. 2016, Vol. 12 72 Ivyspring International Publisher International Journal of Biological Sciences 2016; 12(1): 72-86. doi: 10.7150/ijbs.13188 Research Paper Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways Hongming Lv1#, Zhenxiang Yu2#, Yuwei Zheng1, Lidong Wang1, Xiaofeng Qin1, Genhong Cheng1, Xinxin Ci1 1. Institute of Translational Medicine, The First Hospital of Jilin University, College of Veterinary Medicine, Jilin University, Changchun, China 2. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China. # These authors contributed equally to this work. Corresponding author: X.-X.Ci, Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, 130001, China. Tel.: +86 431 88783044; E-mail addresses: [email protected] (X.-X.Ci.) © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. Received: 2015.07.08; Accepted: 2015.11.02; Published: 2016.01.01 Abstract Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS.
    [Show full text]
  • Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids
    Article Characterization of the CYP3A4 Enzyme Inhibition Potential of Selected Flavonoids Martin Kondža 1 , Mirza Boji´c 2,* , Ivona Tomi´c 1, Željan Maleš 2 , Valentina Rezi´c 3 and Ivan Cavar´ 4 1 Faculty of Pharmacy, University of Mostar, Matice Hrvatske bb, 88000 Mostar, Bosnia and Herzegovina; [email protected] (M.K.); [email protected] (I.T.) 2 University of Zagreb Faculty of Pharmacy and Biochemistry, Ante Kovaˇci´ca1, 10000 Zagreb, Croatia; [email protected] 3 Farmavita d.o.o., Igmanska 5A, 71000 Sarajevo, Bosnia and Herzegovina; [email protected] 4 Faculty of Medicine, University of Mostar, Zrinskog Frankopana 34, 88000 Mostar, Bosnia and Herzegovina; [email protected] * Correspondence: [email protected]; Tel.: +385-1-4818-304 Abstract: Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. For the determination of inhibition kinetics, nifedipine oxidation was used as a marker reaction. A hemochromopyridine test was used to assess the possible covalent binding to the heme, and incubation with dialysis was used in order to assess the reversibility of the inhibition.
    [Show full text]
  • Science Based Authentication of Dietary Supplements
    University of Mississippi eGrove Electronic Theses and Dissertations Graduate School 2010 Science Based Authentication of Dietary Supplements: Studies on the Chemical Constituents, Analytical Method and Biological Activities of Scutellaria Spp and Pfaffiaaniculata P Jing Li Follow this and additional works at: https://egrove.olemiss.edu/etd Part of the Plant Sciences Commons Recommended Citation Li, Jing, "Science Based Authentication of Dietary Supplements: Studies on the Chemical Constituents, Analytical Method and Biological Activities of Scutellaria Spp and Pfaffiaaniculata P " (2010). Electronic Theses and Dissertations. 179. https://egrove.olemiss.edu/etd/179 This Dissertation is brought to you for free and open access by the Graduate School at eGrove. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of eGrove. For more information, please contact [email protected]. SCIENCE BASED AUTHENTICATION OF DIETARY SUPPLEMENTS ---STUDIES ON THE CHEMICAL CONSTITUENTS, ANALYTICAL METHOD AND BIOLOGICAL ACTIVITIES OF SCUTELLARIA SPP AND PFAFFIA PANICULATA KUNTZE A Dissertation presented in partial fulfillment of requirements for the degree of Doctor of Philosophy in the Department of Pharmacognosy The University of Mississippi JING LI Nov. 2010 Copyright © 2010 by Jing Li All rights reserved ii ABSTRACT During the last decade, the use of herbal medicine has expanded globally and gained popularity. With the tremendous expansion in the use of herbal medicine worldwide, safety and efficacy as well as quality control of herbal medicines have become more and more issues of concern for both health authorities and the public. Although herbal medicine has been in use for hundreds to thousands years, very limited science-based data exist to explicit its chemical constituents, pharmacological activities and toxicity.
    [Show full text]
  • Antineoplastic Potential of the Vitex Species: an Overview
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas BOLETÍN LATINOAMERICANO Y DEL CARIBE DE PLANTAS MEDICINALES Y AROMÁTICAS 17 (5): 492 - 502 (2018) © / ISSN 0717 7917 / www.blacpma.usach.cl Revisión | Review Antineoplastic potential of the Vitex species: An overview [Potencial antineoplásico de la especie Vitex: una visión general] Manisha Nigam1, Sarla Saklani2, Sergey Plygun3,4 & Abhay Prakash Mishra2 1Department of Biochemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal, 246174, Uttarakhand, India 2Department of Pharmaceutical Chemistry, H. N. B. Garhwal (A Central) University, Srinagar Garhwal, 246174, Uttarakhand, India 3All Russian Research Institute of Phytopathology, Moscow Region, Russia 4European Society of Clinical Microbiology and Infectious Diseases, Basel, Switzerland Contactos | Contacts: Abhay Prakash MISHRA - E-mail address: [email protected] Abstract: Irrespective of progressive treatments, cancer remains to have the utmost rate of treatment failure due to numerous reasons associated. In recent years, the use of traditional medicine in cancer research has established considerable interest. Natural products represent an amazing source for cancer therapy and combating associated side-effects. More than thousand plants have been found to possess significant anticancer properties. Vitex is the largest genus in the family Lamiaceae which comprises 250 species distributed throughout world and several species have been reported to have anticancer properties. Despite a long tradition of use of some species, the genus has not been explored properly in terms of its anticancer profile. Here we are reporting the updated knowledge of the antineoplastic profile of this genus available so far.
    [Show full text]