DOCSLIB.ORG

Biodistribution of Arctigenin-Loaded Nanoparticles Designed For

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Biodistribution of Arctigenin-Loaded Nanoparticles Designed For Cui et al. J Nanobiotechnol (2017) 15:27 DOI 10.1186/s12951-017-0263-8 Journal of Nanobiotechnology RESEARCH Open Access Biodistribution of arctigenin‑loaded nanoparticles designed for multimodal imaging Qingxin Cui1‡, Yuanyuan Hou1‡, Yanan Wang2, Xu Li3, Yang Liu1, Xiaoyao Ma1, Zengyong Wang1, Weiya Wang1, Jin Tao1, Qian Wang1, Min Jiang1, Dongyan Chen3, Xizeng Feng2* and Gang Bai1* Abstract Background: Tracking targets of natural products is one of the most challenging issues in felds ranging from phar- macognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a “key” that opens the target “lock”. Results: We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were char- acterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM). In addition, we studied the localization of ATG at the level of the cell and the whole animal (zebrafsh and mice). We demonstrated that fuorescent NPs could be ideal carriers in the development of a feasible method for target identif- cation. The distributions of the target proteins were found to be consistent with the pharmacological action of ATG at the cellular and whole-organism levels. Conclusions: The results indicated that functionalized poly-lysine NPs could be valuable in the multimodal imaging of arctigenin. Keywords: Nanoparticles, Self-assembly, Arctigenin, Localization, Target identifcation Background exploring targets of natural products is an immense Natural products have supplied a myriad of compounds undertaking, although many successful methods for with complex structures as well as diverse biological identifying targets of small molecules have been reported activities. Conventional natural products research, which [5], such as FG-beads technology [6], photoafnity beads involves structural determinations and chemical syn- technology [7], the fshing-rod strategy [8], the “compact” theses of complex natural products, was highly success- molecular probe (CMP) approach [9], the yeast 3-hybrid ful until the 1980s. Unfortunately, such research became (Y3H) system [10], and the database-dependent (DBD) less productive in the 1990s [1, 2]. It has become signif- strategy [11, 12]. Tese technologies have conventionally cantly more difcult to fnd the targets of natural prod- been used for identifying targets of small molecules [13]; ucts or discover new concepts in chemistry and biology however, the most serious failing of these approaches is from natural product binding. Terefore, natural prod- the difculty in target tracking in situ [14]. Although the ucts research needs to employ novel strategies based on use of quantum dots for tags could solve the problem targets that are involved in biological phenomena and of target labeling, the fact that these probes are so large processes [3, 4]. However, it is widely recognized that that their localization is not totally in situ cannot not be ignored. More importantly, the problems of obtaining *Correspondence: [email protected]; [email protected] the localization information of the target protein from †Qingxin Cui and Yuanyuan Hou contributed equally to this work the body, tissue or cells, excluding non-specifc protein 1 College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People’s Republic of China interference, and elucidating the relationship between 2 State Key Laboratory of Medicinal Chemical Biology, College of Life the corresponding bioactivity and indications remain a Science, Nankai University, Tianjin 300071, China challenge. Full list of author information is available at the end of the article © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Cui et al. J Nanobiotechnol (2017) 15:27 Page 2 of 10 Recently, it was discovered that some nanoparticles Bainafo Bioengineering Co., Ltd. (Henan, China). NHS- (NPs) with unique physical properties have wide usage rhodamine and sulfo-SADP were purchased from Pierce in a variety of felds, such as the life sciences, pharma- (Rockford, U.S.A.). All other chemicals and solvents used cology, and the environmental sciences [15–18]. Inter- were analytical grade. Te water used throughout this estingly, NPs are an important tool, which had drawn work was reagent-grade water produced by the Milli- signifcant attention in the felds of molecule imaging Q Water Purifcation System of Nihon Millipore Ltd. and protein capturing [19, 20]. Te past 5 years have wit- (Tokyo, Japan). nessed several advances that have established lumines- cent NPs as a highly sensitive technology for real-time The self‑assembly and modifcation of poly‑lysine optical imaging in small animals [21, 22]. Additionally, fuorescent NPs recent developments have demonstrated that such NPs Briefy, peptide solutions were prepared by dissolving the could be directed against specifc cells through proper poly-lysine powder (100 mg, 5 μmol) in 10 mL of phos- surface functionalization with targeting ligands [23, 24]. phate-bufered saline (PBS) bufer (pH 7.4), and then Despite great efort being devoted to the development of NHS-rhodamine (2 mg, 3.8 μmol) was thoroughly dis- bio-functional self-assembling materials [25], the use of persed in an ultrasonic bath. In a reactor equipped with self-assembling NPs in identifying natural product tar- a stirrer, an organic mixture of 200# petrol (13 mL), tet- gets is largely unexplored. Indeed, imaging in multiple rachloromethane (12 mL), and span-80 (1 mL) (1/1/0.08, organisms could prove to be a powerful analytical tool in v/v/v, respectively) were stirred for 30 min at room tem- revealing the targets of natural products. perature. Te mixture of the organic and peptide solu- In this strategy, we used arctigenin (ATG), a phenyl tions was thoroughly dispersed using a homogenizer propanoid dibenzyl butyrolactone lignan from Arctium (FA25, Fluco, England), added to the reactor, and dis- lappa L. (commonly known as burdock) as a model com- persed at 12,000 rpm. Subsequently, petroleum ether pound. It has been widely used in traditional Chinese was added slowly to the mixture. Immediately after the medicine (TCM) and in Europe and North America for delamination process, PBS solution was added, and hundreds of years [26, 27]. Te biological activities and self-assembly occurred during the biphasic equilibrium pharmacological functions reported for ATG include process to room temperature. Te aqueous phase was anti-infammatory, anti-cancer, anti-diabetic, anti-heat collected, and the process was repeated 3 times to obtain shock, antimicrobial and antiviral activities [27–31]. In poly-lysine fuorescent NPs. Te crude product was cen- particular, the target identifcation process may lead to trifuged for 10 min at 1000 rpm, and the precipitate was the discovery biologically intriguing phenomena that discarded. Finally, the supernatant was centrifuged for could open up new frontiers in chemical biology. 10 min at 12,000 rpm. Te supernatant fuid contain- Terefore, we attempted to investigate the targets of ing the poly-lysine fuorescent self-assembling NPs was ATG using self-assembling NPs. We report here that the stored at 4 °C. use of ATG conjugated poly-lysine fuorescent NPs would Sulfo-SADP (15 mg, 0.03 mmol) was dissolved in be advantageous in such cases; they enable visualization 0.2 mL of borate bufer (0.2 mol/L pH 8.0), and 1 mL in contrast to afnity beads, and afnity between the poly-lysine fuorescent NPs was added. Te mixture ligand and its target is retained. By using the self-assem- was stirred at room temperature for 4 h. Te azide func- bling NP strategy, we succeeded in imaging the cytosolic tionalized poly-lysine fuorescent NPs were collected by target protein of ATG in vivo. Tis integrated system ultrafltration (Millipore, USA) and washed with 20 mL solved the issue of a natural product interacting with of phosphate-bufered saline (PBS, pH 7.4) several times multiple targets and turning on diverse biological activi- until sulfo-SADP could no longer be detected in the fl- ties. Tis technique may help discover the targets of natu- trate. Te general strategy for synthesis of blank fuores- ral products and beneft drug research and development. cent NPs (BF NPs) is shown in Fig. 1A. Methods Drug conjugation to poly‑lysine fuorescent NPs Reagents and materials Te synthesis of alkynyl-ATG is depicted in the elec- Propargylic acid was purchased from Sigma-Aldrich tronic Additional fle 1 (scheme 1). Alkynyl-ATG (17 mg, (St. Louis, U.S.A.). N-Hydroxysuccinimide (NHS) and 0.04 mmol) was dissolved in 0.2 mL of borate bufer 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (0.2 mol/L pH 8.0), and 2 mL of azide BF NPs was added, were purchased from Alfa Aesar (Massachusetts, U.S.A.). followed by the catalyst (0.2 mmol/L Tris-triazoleamine, Arctigenin (ATG) was purchased from Phytomarker Co., 1.0 mmol/L CuSO4, and 2.0 mmol/L sodium ascorbate). Ltd. (Tianjin, China). Poly-lysine with an average molec- Te mixture was stirred at room temperature for 1 h. ular weight of 20 kDa was purchased from Zhengzhou Te functionalized NPs were was added to a 50 mL 3kD Cui et al. J Nanobiotechnol (2017) 15:27 Page 3 of 10 Fig. 1 The characterization of NPs. A The general strategy for the synthesis of blank fuorescent NPs (BF NPs) and ATG conjugated poly-lysine fuo- rescent NPs (AF NPs).
Load more

Recommended publications
  • Ilamycin C Induces Apoptosis and Inhibits Migration and Invasion In
    Xie et al. Journal of Hematology & Oncology (2019) 12:60 https://doi.org/10.1186/s13045-019-0744-3 RESEARCH Open Access Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway Qing Xie1†, Zhijie Yang2†, Xuanmei Huang1, Zikang Zhang1, Jiangbin Li1, Jianhua Ju2*, Hua Zhang1* and Junying Ma2* Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Sea- derived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. Methods: CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. Results: In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells.
    [Show full text]
  • Thromboxane A2 Receptor Antagonist SQ29548 Attenuates SH‑SY5Y Neuroblastoma Cell Impairments Induced by Oxidative Stress
    INTERNATIONAL JOURNAL OF MOleCular meDICine 42: 479-488, 2018 Thromboxane A2 receptor antagonist SQ29548 attenuates SH‑SY5Y neuroblastoma cell impairments induced by oxidative stress GAOYU CAI1*, AIJUAN YAN2*, NINGZHEN FU3 and YI FU1 1Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025; 2Department of Neurology, Xin Hua Hospital, Shanghai Jiao Tong University, Shanghai 200082; 3Department of Pancreatic Surgery, Rui Jin College of Clinical Medicine, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025, P.R. China Received September 28, 2017; Accepted March 21, 2018 DOI: 10.3892/ijmm.2018.3589 Abstract. Thromboxane A2 receptor (TXA2R) serves a vital SQ29548, an antagonist of TXA2R, improved the antioxidant role in numerous neurological disorders. Our previous study capacities of SH-SY5Y cells and reduced the cell apoptosis indicated that SQ29548, an antagonist of TXA2R, attenuated through the inhibition of MAPK pathways. the induced neuron damage in cerebral infarction animals; however, the underlying mechanism remains unknown. Introduction Certain studies revealed a new role of TXA2R in the regula- tion of oxidative stress, which is one of the basic pathological Thromboxane A2 receptor (TXA2R), a member of the G processes in neurological disorders. Thus, the present study protein-coupled receptor family (1), is broadly distributed attempted to examine whether the inhibition of TXA2R with in platelets (2), as well as epithelial (3), smooth muscle (4), SQ29548 helped to protect the nerve cells against oxidative glial and nerve cells in the brain (5). TXA2R is regarded as a stress. SQ29548 was utilized as a TXA2R antagonist, and traditional coagulation and inflammation‑associated receptor, relevant assays were performed to detect the cell viability, which is also closely associated with neurological disorders.
    [Show full text]
  • Supplemetal Materials and Methods Materials Arctiin and Arctigenin
    Supplemetal materials and Methods Materials Arctiin and arctigenin were separated and purified by our laboratory and the final product shown an over 98% purity by HPLC detection. Trandrine tablets were provided by Zhejiang Jinhua Conba Bio-Pharm. CO., LTD. China. Silica (SiO2 purity >99%, particle size 0.5-10 μm (approx. 80% between 1-5 μm) was purchased from Sigma, St., Louse, MO, USA. Penicillin G was suppied by North China Pharmaceutical Co., Ltd. 2-ketoglutaric acid, pyruvic acid, succinic acid, disodium fumarate, malic acid, stearic acid, 3-hydroxytyramine hydrochloride and mixed amino acid standards were purchased from Sigma, USA. Betaine, allantoin, inosine, taurine, creatinine, L-carnitine, creatine, urea and citric acid were recruited from Aladdin, USA. Sodium lactate, doxifluridine, D-(+)-pantothenic acid calcium salt and 6-hydroxypurine were purchased from the National Institutes for Food and Drug Control, China. TNF-α, IL- 1β, NF-κB and TGF-β ELISA kit (FANKEL BIO, Shanghai, China), Hydroxyproline (HYP), ceruloplasmin and lysozyme assay kits (Jiancheng Bioengineering Institute, Nanjing, China). The mitochondrial membrane potential assay kit (Beyotime Biotechnology, Shanghai, China.), reactive oxygen species assay kit (Jiancheng Bioengineering Institute, Nanjing, China.), SDS-PAGE Sample Loading Buffer (Beyotime, Shanghai, China), BCA Protein Assay Kit (Beyotime, Shanghai, China). Antibodies against the following proteins were used: α-SMA, NF-κB, TLR-4, Myd88, NLRP3, ASC, cleaved Caspase-1 (Wanleibio, Shenyang, China), β-actin (Absci, USA), HRP-conjugated goat antirabbit IgG (Wanleibio, Shenyang, China), BeyoECL Plus (Beyotime, Shanghai, China). Dose selection The daily dose interval of Fructus Arctii is 6 - 12 g according to Chinese Pharmacopoeia, in which the arctigenin account for 5% of Fructus Arctii.
    [Show full text]
  • Anti-Toxoplasma Gondii Effects of a Novel Spider Peptide XYP1 in Vitro and in Vivo
    biomedicines Article Anti-Toxoplasma gondii Effects of a Novel Spider Peptide XYP1 In Vitro and In Vivo Yuan Liu 1,†, Yaqin Tang 1,†, Xing Tang 2,†, Mengqi Wu 1, Shengjie Hou 1, Xiaohua Liu 1, Jing Li 1, Meichun Deng 3, Shuaiqin Huang 1 and Liping Jiang 1,4,* 1 Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha 410013, China; [email protected] (Y.L.); [email protected] (Y.T.); [email protected] (M.W.); [email protected] (S.H.); [email protected] (X.L.); [email protected] (J.L.); [email protected] (S.H.) 2 Hunan Key Laboratory for Conservation and Utilization of Biological Resources in the Nanyue Mountainous Region, Hengyang Normal University, Hengyang 421008, China; [email protected] 3 Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha 410013, China; [email protected] 4 China-Africa Research Center of Infectious Diseases, Xiangya School of Medicine, Central South University, Changsha 410013, China * Correspondence: [email protected]; Tel.: +86-731-82650556 † These authors have contributed equally to this work. Abstract: Toxoplasmosis, caused by an obligate intracellular parasite Toxoplasma gondii, is one of the most prevalent zoonoses worldwide. Treatments for this disease by traditional drugs have shown numerous side effects, thus effective alternative anti-Toxoplasma strategies or drugs are urgently needed. In this study, a novel spider peptide, XYP1, was identified from the cDNA library of the Citation: Liu, Y.; Tang, Y.; Tang, X.; venom gland of the spider Lycosa coelestis. Our results showed that XYP1 has potent anti-Toxoplasma Wu, M.; Hou, S.; Liu, X.; Li, J.; Deng, activity in vitro and in vivo.
    [Show full text]
  • BQ123 Stimulates Skeletal Muscle Antioxidant Defense Via Nrf2 Activation in LPS-Treated Rats
    Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2016, Article ID 2356853, 8 pages http://dx.doi.org/10.1155/2016/2356853 Research Article BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS-Treated Rats Agata Kowalczyk,1 Agnieszka JeleN,2 Marta gebrowska,2 Ewa Balcerczak,2 and Anna Gordca1 1 Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland 2Laboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland Correspondence should be addressed to Agata Kowalczyk; [email protected] and Anna Gorąca; [email protected] Received 23 July 2015; Revised 24 September 2015; Accepted 11 October 2015 Academic Editor: Ersin Fadillioglu Copyright © 2016 Agata Kowalczyk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin-A receptor antagonist, influences the level of TNF-, IL-6, SOD-1, HO- 1, Nrf2 mRNA, and NF-B subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (=6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later.
    [Show full text]
  • Modes of Action of Herbal Medicines and Plant Secondary Metabolites
    Medicines 2015, 2, 251-286; doi:10.3390/medicines2030251 OPEN ACCESS medicines ISSN 2305-6320 www.mdpi.com/journal/medicines Review Modes of Action of Herbal Medicines and Plant Secondary Metabolites Michael Wink Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, Heidelberg D-69120, Germany; E-Mail: [email protected]; Tel.: +49-6221-544-881; Fax: +49-6221-544-884 Academic Editor: Shufeng Zhou Received: 13 August 2015 / Accepted: 31 August 2015 / Published: 8 September 2015 Abstract: Plants produce a wide diversity of secondary metabolites (SM) which serve them as defense compounds against herbivores, and other plants and microbes, but also as signal compounds. In general, SM exhibit a wide array of biological and pharmacological properties. Because of this, some plants or products isolated from them have been and are still used to treat infections, health disorders or diseases. This review provides evidence that many SM have a broad spectrum of bioactivities. They often interact with the main targets in cells, such as proteins, biomembranes or nucleic acids. Whereas some SM appear to have been optimized on a few molecular targets, such as alkaloids on receptors of neurotransmitters, others (such as phenolics and terpenoids) are less specific and attack a multitude of proteins by building hydrogen, hydrophobic and ionic bonds, thus modulating their 3D structures and in consequence their bioactivities. The main modes of action are described for the major groups of common plant secondary metabolites. The multitarget activities of many SM can explain the medical application of complex extracts from medicinal plants for more health disorders which involve several targets.
    [Show full text]
  • Overview of the Anti-Inflammatory Effects, Pharmacokinetic Properties
    Acta Pharmacologica Sinica (2018) 39: 787–801 © 2018 CPS and SIMM All rights reserved 1671-4083/18 www.nature.com/aps Review Article Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L Qiong GAO, Mengbi YANG, Zhong ZUO* School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China Abstract Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.
    [Show full text]
  • The Anti-Metastatic Effects of the Phytoestrogen Arctigenin on Human Breast Cancer Cell Lines Regardless of the Status of ER Expression
    INTERNATIONAL JOURNAL OF ONCOLOGY 50: 727-735, 2017 The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression THRESSI MAxwEll, So-YouNg CHuN, KYu-SHIK lEE, SoYouNg KIM and KYuNg-Soo NAM Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk university, gyeongju-si 780-350, Republic of Korea Received August 8, 2016; Accepted December 12, 2016 DoI: 10.3892/ijo.2016.3825 Abstract. Arctigenin is a plant lignan extracted from Arctium were analyzed using western blotting. The activation of Akt, lappa that has been shown to have estrogenic properties. In NF-κB and MAPK (ERK 1/2 and JNK 1/2) was found to be spite of the health benefits of phytoestrogens reducing the risk inhibited. Taken together, these data suggest that arctigenin of osteoporosis, heart disease, and menopausal symptoms, its confers anti-metastatic effects by inhibiting MMP-9 and uPA benefits against the risk of breast cancer have not been fully via the Akt, NF-κB and MAPK signaling pathways on breast elucidated. Thus, we investigated the effects of arctigenin cancer, regardless of ER expression. Therefore, we propose on metastasis of breast cancer using both estrogen receptor that the intake of arctigenin could be an effective supplement (ER)-positive MCF-7 and ER-negative MDA-MB-231 human for breast cancer patients. breast cancer cell lines to see if the effects are dependent on the status of ER expression. In ER-positive MCF-7 cells, Introduction arctigenin efficiently inhibited 12-O-tetradecanoylphorbol- 13-acetate (TPA)-induced cell migration and invasion.
    [Show full text]
  • Investigation of the Antidiabetic Activity Of
    INVESTIGATION OF THE ANTIDIABETIC ACTIVITY OF CNICUS BENEDICTUS L. IN RATS. RAYMONDE BAMBOUKOU BEKALE (B. Pharm, UWC) A thesis submitted in partial fulfilment of the requirements for the degree of Magister Pharmaceuticae in the School of Pharmacy, University of the Western Cape SUPERVISOR: PROFESSOR GEORGE J. AMABEOKU NOVEMBER 2016 i DECLARATION I declare that the thesis, Investigation of the antidiabetic activity of Cnicusbenedictus L. in rats, is my own work, that it has not been submitted before for any degree examination in any other University and that all the sources I have used or quoted have been indicated and acknowledged by complete reference. Raymonde BAMBOUKOU BEKALE November 2016 Signed……………………………….. ii DEDICATION I dedicate this thesis to my loving mother, Boubwetata Loba Helene and my family for their sacrifices and endless love, care and encouragement that has got me to where I am today. Thank you for believing in me and supporting me to be the best. iii ACKNOWLEDGEMENTS First of all, I thank the Almighty God, our Saviour, for His Mercy, Guidance and Protection throughout the years. The completion of this work has come as a product of hard work and I would like to express my sincere gratitude to the following individual and organizations, whose involvement in my life enabled me to complete this thesis: My supervisor, PROFESSOR GEORGE J. AMABEOKU for his commitment, guidance, patience, support, advice and valuable contributions made towards my study. I am privileged to have worked alongside him. The National Research Foundation for financial support. Mrs Eloise for her assistance with laboratory technicalities. MrsVirginaMvula for the maintenance of the animal house and upkeep of the animals.
    [Show full text]
  • Plant. Biotechnol. 30(2)
    Plant Biotechnology 30, 97–109 (2013) DOI: 10.5511/plantbiotechnology.12.1230a Original Paper A lignan O-methyltransferase catalyzing the regioselective methylation of matairesinol in Carthamus tinctorius Toshiaki Umezawa1,2,*,†, Safendrri Komara Ragamustari1,2,†, Tomoyuki Nakatsubo1, Shohei Wada1, Laigeng Li3,4, Masaomi Yamamura1, Norikazu Sakakibara1,5, Takefumi Hattori1,6, Shiro Suzuki1, Vincent L. Chiang3 1 Research Institute for Sustainable Humanosphere, Kyoto University, Uji, Kyoto 611-0011, Japan; 2 Institute of Sustainability Science, Kyoto University, Uji, Kyoto 611-0011, Japan; 3 Department of Forestry and Environmental Resources, College of Natural Resources, North Carolina State University, Raleigh, NC 27695-7247, USA; 4 Institute of Plant Physiology and Ecology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; 5 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan; 6 Institute of Socio-Arts and Sciences, The University of Tokushima, Tokushima 770-8502, Japan * E-mail: [email protected] Tel: +81-774-38-3625 Fax: +81-774-38-3682 Received December 14, 2012; accepted December 30, 2012 (Edited by T. Aoki) Abstract Lignans are a group of plant phenolic compounds with various biological activities, including antitumor and antioxidant properties. O-Methylation is a critical step in biosynthesis of these compounds. However, little is known about the O-methyltransferase (OMT) enzymes that catalyze lignan O-methylation. We discovered a highly regioselective OMT activity in safflower (Carthamus tinctorius) seeds that catalyzed the methylation of matairesinol, a dibenzylbutyrolactone lignan, into 4′-O-methylmatairesinol (arctigenin) but not 4-O-methylmatairesinol (isoarctigenin). By examining such OMT activity in correlation with OMT transcript abundances during seed development, we cloned a few putative OMT cDNAs and produced their recombinant proteins in Escherichia coli.
    [Show full text]
  • Medicinal Plants in the Treatment of Colitis: Evidence from Preclinical Studies
    Reviews Medicinal Plants in the Treatment of Colitis: Evidence from Preclinical Studies Authors ABSTRACT Marília T. Santana, Luana M. Cercato, Janaíne P. Oliveira, Ulcerative colitis is a chronic inflammatory condition whose Enilton A. Camargo treatment includes aminosalicylates, corticosteroids, and im- munomodulators. Medicinal plants seem to be an important Affiliation alternative treatment for this condition. They have been the Department of Physiology, Federal University of Sergipe, subject of a great number of studies in recent years. This São Cristóvão, SE, Brazil study was conducted to systematically review the medicinal plants tested in experimental models of ulcerative colitis. We Key words conducted a systematic literature search through specialized ulcerative colitis, medicinal plant, phytotherapy, flavonoid, databases (PUBMED, SCOPUS, EMBASE, MEDLINE, LILACS, terpene SCIELO, and SCISEARCH) and selected articles published be- tween January 2000 and June 21, 2016 by using “medicinal received November 11, 2016 plants” and “ulcerative colitis” as key words. Sixty-eight stud- revised January 17, 2017 ies were included, and the families Asteraceae and Lamiaceae accepted February 20, 2017 presented the largest number of studies, but plants from sev- Bibliography eral other families were cited; many of them have shown DOI http://dx.doi.org/10.1055/s-0043-104933 good results in experimental animals. However, only a few Published online March 14, 2017 | Planta Med 2017; 83: 588– species (such as Andrographis paniculata and Punica granatum) 614 © Georg Thieme Verlag KG Stuttgart · New York | have undergone clinical tests against ulcerative colitis, and ISSN 0032‑0943 the observation that many preclinical studies reviewed are purely descriptive has certainly contributed to this fact.
    [Show full text]
  • Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer
    International Journal of Molecular Sciences Review Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer Yetirajam Rajesh 1 and Devanand Sarkar 2,* 1 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA; [email protected] 2 Massey Cancer Center, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA * Correspondence: [email protected]; Tel.: +1-804-827-2339 Abstract: Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related Citation: Rajesh, Y.; Sarkar, D. metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their Association of Adipose Tissue and role as potential therapeutic targets.
    [Show full text]