DOCSLIB.ORG

Theacrine Attenuates Myocardial Fibrosis After Myocardial Infarction Via the SIRT3/Β-Catenin/ Pparγ Pathway in Estrogen-Deficient Mice

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Theacrine Attenuates Myocardial Fibrosis After Myocardial Infarction Via the SIRT3/Β-Catenin/ Pparγ Pathway in Estrogen-Deficient Mice European Review for Medical and Pharmacological Sciences 2019; 23: 5477-5486 Theacrine attenuates myocardial fibrosis after myocardial infarction via the SIRT3/β-catenin/ PPARγ pathway in estrogen-deficient mice L.-L. SONG1, Y. ZHANG2, X.-R. ZHANG3, Y.-N. SONG4, H.-Z. DAI5 1Department of Critical Care Medicine, Weifang Hanting District People’s Hospital, Weifang, China 2Department of Respiratory Medicine, Weifang Hanting District People’s Hospital, Weifang, China 3Department of Pharmacology, Weifang Medical University, Weifang, China 4Department of Breast and Thyroid Surgery, The Traditional Chinese Medicine Hospital of Weifang, Weifang, China 5Department of Emergency, The Affiliated Hospital of Weifang Medical University, Weifang, China Abstract. – OBJECTIVE: To investigate the myocardial apoptosis were clearly aggravated, role of theacrine in the protection of ventricular and the SIRT3 expression was decreased at 28 remodeling and chronic heart failure after myo- days after myocardial infarction. The theacrine cardial infarction in the estrogen-deficient mice. could improve the cardiac function after the MATERIALS AND METHODS: Female myocardial infarction in estrogen-deficient mice C57BL/6 mice aged 8 weeks old were selected and relieve both myocardial fibrosis and myo- and then subjected to bilateral oophorectomy. cardial apoptosis during chronic remodeling af- At 7 days after surgery, the models of the myo- ter myocardial infarction in estrogen-deficient cardial infarction were established by ligating mice. After the intervention with theacrine, the the anterior descending coronary artery. On the estrogen-deficient mice with myocardial infarc- first day after myocardial infarction, Theacrine tion had up-regulated SIRT3 and PPARγ levels (20 mg/kg) was administered via gavage for con- and a reduced β-catenin level in the heart. tinuous 28 days. Thereafter, the cardiac function CONCLUSIONS: Theacrine is able to acti- in each group of mice was detected via cardiac vate SIRT3 and repress myocardial fibrosis and ultrasonography for small animals at 7, 14, and apoptosis after myocardial infarction in ovariec- 28 days after surgery. The mice were sacrificed tomized mice, thereby improving the cardiac after 28 days. The infarct size of mice was deter- function of ovariectomized mice with myocardi- mined through 2,3,5-triphenyltetrazolium chlo- al infarction through the possible downstream ride (TTC) and Evan blue double staining assay, signal pathway β-catenin/PPARγ. while the myocardial fibrosis was assessed via Key Words Masson staining assay. The expression levels of Theacrine, Myocardial infarction, Estrogen-defi- collagen-related proteins Collagen I, Collagen cient, Myocardial fibrosis, SIRT3/β-catenin/PPARγ. III, alpha-smooth muscle actin (α-SMA), and the transforming growth factor-β (TGF-β) were mea- sured by Western blotting (WB). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay was applied to evaluate the myocardial apopto- Introduction sis, and the WB was employed to detect apop- tosis-associated proteins. The expression level Acute myocardial infarction is one of the most of silent information regulator 2 homologue 3 1 (SIRT3) protein was detected by immunohisto- severe coronary heart diseases . The mortality chemistry, and the expression levels of SIRT3, rate of coronary heart diseases shows a decreas- β-catenin and peroxisome proliferator-activated ing tendency in the past decade due to changes in receptor gamma (PPARγ) protein were measured evidence-based therapeutic methods and lifestyles, via WB. RESULTS: but myocardial infarction is still a global disease Compared with those in the Sham seriously endangering human health2. Moreover, group, the ejection fraction (EF) and fractional shortening (FS) in estrogen-deficient mice were the incidence and mortality rates of the coronary significantly lowered, the myocardial fibrosis and heart diseases are evidently increased in elderly Corresponding Author: Huizhen Dai, BM; e-mail: [email protected] 5477 L.-L. Song, Y. Zhang, X.-R. Zhang, Y.-N. Song, H.-Z. Dai women because of their decreased estrogen levels Materials and Methods after menopause3,4. Once myocardial infarction is detected, the mortality rate for women is signifi- Laboratory Animals and Models cantly higher than that for men5,6. Since the risks The subjects of this study were female C57BL/6 for cardiovascular diseases, as well as venous mice aged 8 weeks old and weighing 18-20 g, pur- thrombosis and stroke, are increased after estrogen chased from the Model Animal Research Center replacement therapy, estrogen is not recommended of Weifang Medical University. They were housed as a measure to prevent and treat coronary heart in the Specific Pathogen Free (SPF)-level animal diseases in postmenopausal women at present7,8. room. Experimentation on animals was approved Therefore, it is particularly important to find ef- by the Animal Ethics Committee of Weifang Med- fective drugs for preventing and treating coronary ical University. Bilateral oophorectomy: a mouse heart diseases in postmenopausal women. was anesthetized via intraperitoneal injection of More attention has been paid to the left the 400 mg/kg chloral hydrate and then fixed on an ventricular remodeling after myocardial infarc- operating table, followed by the disinfection of tion9-11. Left ventricular remodeling severely the skin. Thereafter, with the intersections of the weakens the left ventricular function in patients mouse’s right and left thigh root connection lines with myocardial infarction and significantly in- and the median line on the back as starting points, creases the complication and the mortality rates the surgical incisions (about 1 cm) directing to the in patients12,13. Myocardial fibrosis, whose extent head were made. Taking the right ovary as an ex- is one of the main factors determining the prog- ample, the skin incision was pulled to the right side nosis in patients with cardiovascular diseases, is by about 0.5 cm. The ovary is located in the fat an important feature of myocardial remodeling12. mass next to the lower kidney. Then, the muscle Sirtuins, a class of NAD+-dependent deacety- layer on the surface of the fat mass was bluntly sep- lases, play vital roles in regulating cell growth, arated, and the ovary was resected. Next, the left metabolism, senescence, stress, and apoptosis14. ovary was removed in the same way. After that, Among them, the silent information regulator 2 the skin was sutured, and the mouse was placed on homologue 3 (SIRT3) is important for the preven- a warm table for recovery. Establishment of myo- tion and treatment of cardiovascular diseases, and cardial infarction models: a mouse was intraperi- it is able to suppress the myocardial apoptosis and toneally injected with 400 mg/kg chloral hydrate delay the cardiac hypertrophy and heart failure15,16. for anesthetization, and then fixed on the operat- Besides, SIRT3 exerts an important protective ef- ing table in the supine position. After that, peroral fect on organ fibrosis17,18. The overexpression of non-invasive endotracheal intubation was conduct- SIRT3 protects bleomycin-induced pulmonary ed using a self-made trachea cannula, and a venti- fibrosis19. SIRT3-KO mice spontaneously have lator was connected to control breathing (frequen- myocardial fibrosis at the th8 week after birth20. cy: 90-100 breaths/min, tidal volume: 0.4-0.5 mL). Resveratrol activates SIRT3 and inhibits myo- Thereafter, the surgical area was disinfected, and a cardial fibrosis by regulating the transforming transverse incision was made on the skin in the left growth factor-β (TGF-β)/SMAD signaling path- fourth intercostal space, followed by blunt dissec- way, thereby improving cardiac function21. tion of the pectoralis major and anterior serratus to Theacrine, namely 1,3,7,9-tetramethyluric expose the heart. Next, the pericardium was cut to acid (molecular formula: C9H12N4O3), is a purine expose the left auricle and the left ventricle, and a alkaloid, which has a similar structure to that of 7-0 non-invasive surgical suture fine needle with caffeine. Studies22,23 on the pharmacological ac- thread was used to suture and ligature the coro- tivity of theacrine mainly focus on its regulato- nary artery at 2-3 mm below the lower edge of the ry role in the central nervous system. In recent left auricle. After the ligation succeeded, it could years, a research24 has discovered that theacrine be observed that the cardiac muscle in the ligated activates SIRT3 protein, and is a novel SIRT3 ag- area became white. The chest was closed layer by onist. So far, the effect of theacrine on myocardial layer, and the surgical incision was applied exter- infarction is not reported. Therefore, in this work, nally with erythromycin eye ointment, followed by the models of the myocardial infarction were es- observation. The tracheal intubation was removed tablished in estrogen-deficient mice to explore the after waking up, and then the mouse was put back influence of theacrine on cardiac function and to the rearing cage. On the first day after myocar- myocardial remodeling and investigate its possi- dial infarction, Theacrine (20 mg/kg) was admin- ble mechanism of action. istered via gavage for continuous 28 days. 5478 Theacrine attenuates myocardial fibrosis after myocardial infarction Determination of Cardiac Structure immersed with gradient ethanol for 3 min, and and Cardiac Function in Mice treated with Proteinase K working solution for
Load more

Recommended publications
  • (12) United States Patent (10) Patent No.: US 9.468,645 B2 Owoc (45) Date of Patent: Oct
    USOO9468645B2 (12) United States Patent (10) Patent No.: US 9.468,645 B2 OWOc (45) Date of Patent: Oct. 18, 2016 (54) HIGHLY SOLUBLE PURINE BOACTIVE (2013.01); A61K 9/0019 (2013.01); A61 K COMPOUNDS AND COMPOSITIONS 9/0095 (2013.01); A61K 9/4858 (2013.01); THEREOF A61 K3I/00 (2013.01); A61K 45/06 (2013.01); A23 V 2002/00 (2013.01) (71) Applicant: JHO Intellectual Property Holdings, (58) Field of Classification Search LLC, Davie, FL (US) CPC ..................... A23V 2002/00; A23V 2200/31; (72) Inventor: Jack Owoc, Weston, FL (US) A23V 2250/062: A23V 2250/21: A23V 2250/5108: A23V 2250/5118: A23V (*) Notice: Subject to any disclaimer, the term of this 2250/54246; A23V 2250/54252: A23V patent is extended or adjusted under 35 2250/704; A23V 2250/712: A61K 31/522; U.S.C. 154(b) by 3 days. A61K 2300/00; A61K 45/06; A61 K9/00 See application file for complete search history. (21) Appl. No.: 14/628,626 (56) References Cited (22) Filed: Feb. 23, 2015 U.S. PATENT DOCUMENTS (65) Prior Publication Data 837,282 A * 12/1906 Owoc ....................... EO1B 9/60 US 2015/O238494 A1 Aug. 27, 2015 238,292 5,973,005 A * 10/1999 D'Amelio, Sr. ... CO7C 277/08 514,565 Related U.S. Application Data 2006/0236421 A1* 10, 2006 Pennell ................ C12N 9/1007 800,278 (60) Provisional application No. 61/944,528, filed on Feb. 2009,0257997 A1* 10, 2009 Owoc .................. A61K9/0014 25, 2014. 424/94.1 (51) Int. C. * cited by examiner A6 IK3I/522 (2006.01) A6 IK 45/06 (2006.01) Primary Examiner – Debbie K Ware A2.3L 2/52 (2006.01) (74) Attorney, Agent, or Firm — David W.
    [Show full text]
  • Identification and Characterization of N 9-Methyltransferase Involved In
    ARTICLE https://doi.org/10.1038/s41467-020-15324-7 OPEN Identification and characterization of N9- methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea Yue-Hong Zhang1,2,3,6, Yi-Fang Li1,2,3,6, Yongjin Wang1,3,6, Li Tan1,3, Zhi-Qin Cao1,2,3, Chao Xie1,2,3, Guo Xie4, Hai-Biao Gong1,2,3, Wan-Yang Sun1,2,3, Shu-Hua Ouyang1,2,3, Wen-Jun Duan1,2,3, Xiaoyun Lu1,3, Ke Ding 1,3, ✉ ✉ ✉ ✉ Hiroshi Kurihara1,2,3, Dan Hu 1,2,3 , Zhi-Min Zhang 1,3 , Ikuro Abe 5 & Rong-Rong He 1,2,3 1234567890():,; Caffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. Due to its occasional side effects, reduction of caffeine in a natural way is of great importance and economic significance. Recent studies reveal that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha (Kucha), which involves oxidation at the C8 and methylation at the N9 positions of caffeine. However, the underlying molecular mechanism remains unclear. Here, we identify the theacrine synthase CkTcS from Kucha, which possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation. The crystal structure of the CkTcS complex reveals the key residues that are required for the N9-methylation, providing insights into how caffeine N-methyltransferases in tea plants have evolved to catalyze regioselective N-methylation through fine tuning of their active sites.
    [Show full text]
  • Pharmacokinetics of Caffeine: a Systematic Analysis of Reported Data
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.12.452094; this version posted August 3, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Pharmacokinetics of caffeine: A systematic analysis of reported data for application in metabolic phenotyping and liver function testing Jan Grzegorzewski 1, Florian Bartsch 1, Adrian Koller¨ 1, and Matthias Konig¨ 1;∗ 1Institute for Theoretical Biology, Humboldt-University Berlin, Invalidenstraße 110, 10115 Berlin, Germany Correspondence*: Matthias Konig¨ [email protected] ABSTRACT Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and theophylline. Besides its stimulating properties, two important applications of caffeine are metabolic phenotyping of cytochrome P450 1A2 (CYP1A2) and liver function testing. An open challenge in this context is to identify underlying causes of the large inter-individual variability in caffeine pharmacokinetics. Data is urgently needed to understand and quantify confounding factors such as lifestyle (e.g. smoking), the effects of drug-caffeine interactions (e.g. medication metabolized via CYP1A2), and the effect of disease. Here we report the first integrative and systematic analysis of data on caffeine pharmacokinetics from 148 publications and provide a comprehensive high-quality data set on the pharmacokinetics of caffeine, caffeine metabolites, and their metabolic ratios in human adults. The data set is enriched by meta-data on the characteristics of studied patient cohorts and subjects (e.g.
    [Show full text]
  • Caffeine and Chlorogenic Acid Contents Among Wild Coffea
    Food Chemistry Food Chemistry 93 (2005) 135–139 www.elsevier.com/locate/foodchem Qualitative relationship between caffeine and chlorogenic acid contents among wild Coffea species C. Campa, S. Doulbeau, S. Dussert, S. Hamon, M. Noirot * Centre IRD of Montpellier, B.P. 64501, 34394 Montpellier Cedex 5, France Received 28 June 2004; received in revised form 13 October 2004; accepted 13 October 2004 Abstract Chlorogenic acids, sensu largo (CGA), are secondary metabolites of great economic importance in coffee: their accumulation in green beans contributes to coffee drink bitterness. Previous evaluations have already focussed on wild species of coffee trees, but this assessment included six new taxa from Cameroon and Congo and involved a simplified method that generated more accurate results. Five main results were obtained: (1) Cameroon and Congo were found to be a centre of diversity, encompassing the entire range of CGA content from 0.8% to 11.9% dry matter basis (dmb); (2) three groups of coffee tree species – CGA1, CGA2 and CGA3 – were established on the basis of discontinuities; (3) means were 1.4%, 5.6% and 9.9% dmb, respectively; (4) there was a qualitative relation- ship between caffeine and ACG content distribution; (5) only a small part of the CGA is trapped by caffeine as caffeine chlorogenate. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Coffeae; Caffeine; Chlorogenic acids 1. Introduction lic acid [feruloylquinic acids (FQA)] and represent 98% of all CGAs (Clifford, 1985; Morishita, Iwahashi, & Two coffee species, C. canephora and C. arabica, are Kido, 1989). There are also some minor compounds, cultivated worldwide. However, these species only repre- such as esters of feruloyl-caffeoylquinic acids (FCQA), sent a small proportion of the worldÕs coffee genetic re- caffeoyl-feruloylquinic acids (CFQA) or p-coumaric acid sources as, in the wild, the Coffea subgenus (Coffea (p-CoQA).
    [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]
  • The Two Tortoitumia Ultimate Tatli Himin
    THETWO TORTOITUMIAUS 20180104248A1ULTIMATE TATLI HIMIN ( 19) United States ( 12) Patent Application Publication ( 10 ) Pub . No. : US 2018 /0104248 A1 Lopez et al. (43 ) Pub . Date : Apr . 19 , 2018 ( 54 ) THEACRINE -BASED SUPPLEMENT AND Publication Classification METHOD OF USE THEREOF IN A (51 ) Int. Cl. SYNERGISTIC COMBINATION WITH A61K 31/ 522 ( 2006 . 01 ) CAFFEINE C07D 487/ 04 (2006 . 01) (52 ) U . S . CI. @( 71 ) Applicant : Ortho - Nutra, LLC , Morganville , NJ CPC .. A61K 31/ 522 ( 2013 .01 ) ; C07D 487 /04 (US ) ( 2013. 01 ) @(72 ) Inventors : Hector L Lopez , Cream Ridge , NJ (US ) ; Shawn Wells , Lewisville , TX (US ) ; Tim N . Ziegenfuss , Chardon , OH (57 ) ABSTRACT (US ) A human dietary supplement comprises theacrine and @( 73 ) Assignee : Ortho -Nutra , LLC , Morganville , NJ optionally other compounds that modulate the effects of theacrine . Uses for the theacrine - containing supplement (US ) include improvement of at least one ofmood , energy, focus, concentration or sexual desire or a reduction of at least one (21 ) Appl. No. : 15 /600 , 371 of anxiety or fatigue. A synergistic composition comprises ( 22 ) Filed : May 19 , 2017 co -administration of theacrine and caffeine , wherein the co - administered caffeine reduces theacrine oral clearance Related U . S . Application Data (CL / F ) and oral volume of distribution (Vd / F ) . In addition , the co - administered caffeine increases area under the plasma (63 ) Continuation - in -part of application No. 14 / 539, 726 , concentration time curve ( AUC ) of theacrine , and increases filed on Nov. 12 , 2014 . theacrine maximum plasma concentration ( Cmax ) in com (60 ) Provisional application No .61 / 903 ,362 , filed on Nov . parison with the corresponding pharmacokinetic parameters 12 , 2013 .
    [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 Effects of Teacrine and Caffeine on Endurance and Cognitive
    THE EFFECTS OF TEACRINE AND CAFFEINE ON ENDURANCE AND COGNITIVE PERFORMANCE DURING A SIMULATED MATCH IN HIGH-LEVEL SOCCER PLAYERS By MARISSA L. BELLO A thesis submitted to the School of Graduate Studies Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Master of Science Graduate Program in Kinesiology and Applied Physiology Written under the direction of Shawn M. Arent And approved by ___________________ ___________________ ___________________ New Brunswick, NJ [January 2019] ABSTRACT OF THE THESIS The Effects of Teacrine and Caffeine on Endurance and Cognitive Performance During a Simulated Match in High-Level Soccer Players by MARISSA L. BELLO Thesis Director Shawn M. Arent Theacrine (1,3,7,9-tetramethyluric-acid) is a pure alkaloid with a similar structure to caffeine and acts comparably as an adenosine receptor antagonist. Early studies have shown non-habituating effects, including increases in energy, focus, and concentration in Teacrine®, the compound containing pure theacrine. PURPOSE: to determine and compare the effects of Teacrine® and caffeine on cognitive performance and time-to-exhaustion during a simulated soccer game in high- level male and female athletes. METHODS: Elite male and female soccer players (N=24; MAge=20.96±2.05y, MMaleVO2max=55.31±3.39mL/O2/kg, MFemaleVO2max=50.97±3.90mL/O2/kg) completed a simulated 90-min soccer match protocol on a treadmill, with cognitive testing including simple reaction time (SRT); choice-RT during a go/no-go task (CRT); and complex-RT during a dual task of go/no go (COGRT) with distraction questions at halftime, and end-of-game.
    [Show full text]
  • LC–MS/MS) Method for Characterizing Caffeine, Methylliberine, and Theacrine Pharmacokinetics in Humans Yan-Hong Wanga, Goutam Mondala, Matthew Butawanb, Richard J
    Journal of Chromatography B 1155 (2020) 122278 Contents lists available at ScienceDirect Journal of Chromatography B journal homepage: www.elsevier.com/locate/jchromb Development of a liquid chromatography-tandem mass spectrometry T (LC–MS/MS) method for characterizing caffeine, methylliberine, and theacrine pharmacokinetics in humans Yan-Hong Wanga, Goutam Mondala, Matthew Butawanb, Richard J. Bloomerb, ⁎ Charles R. Yatesa,c, a The National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA b Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, TN, USA c NPI, LLC, Oxford, MS, USA ARTICLE INFO ABSTRACT Keywords: Coffea liberica possesses stimulant properties without accumulating the methylxanthine caffeine. The basis for LC-MS/MS this peculiar observation is that methylurates (e.g., theacrine and methylliberine) have replaced caffeine. The Caffeine stimulant properties of methylurates, alone and in combination with caffeine, have recently been investigated. Methylliberine However, human pharmacokinetics and LC-MS/MS methods for simultaneous measurement of methylxanthines Theacrine and methylurates are lacking. To address this deficiency, we conducted a pharmacokinetic study in which Human pharmacokinetics subjects (n = 12) were orally administered caffeine (150 mg), methylliberine (Dynamine™, 100 mg), and theacrine (TeaCrine®, 50 mg) followed by blood sampling over 24 h. Liquid-liquid extraction of plasma samples containing purine alkaloids and internal standard (13C-Caffeine) were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to detect caffeine, methylliberine, theacrine, and IS tran- sitions of m/z 195.11 → 138.01, 225.12 → 168.02, 225.12 → 167.95, and 198.1 → 140.07, respectively.
    [Show full text]
  • Assessment of Pharmacokinetic Interaction Potential Between Caffeine and Methylliberine
    medRxiv preprint doi: https://doi.org/10.1101/2021.01.05.21249234; this version posted January 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Assessment of Pharmacokinetic Interaction Potential Between Caffeine and Methylliberine Running Title: Pharmacokinetics of Dynamine Authors: Goutam Mondal, PhD1 Yan-Hong Wang, PhD1 Matthew Butawan, BS2 Richard J. Bloomer, PhD2 Charles R. Yates, PharmD, PhD1,3 Affiliations: 1The National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA 2Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, TN, USA 3NPI, LLC, Oxford, MS Correspondence should be sent to: Charles R. Yates Thad Cochran Research Center West National Center for Natural Products Research Oxford, MS, 38677-1848 Phone: (662) 915-6994 Email: [email protected] Key Words: caffeine, methylliberine, theacrine, and pharmacokinetics NOTE: This preprint reports new research that has not been certified1 by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.01.05.21249234; this version posted January 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Methylliberine and theacrine are methylurates found in the leaves of various Coffea species and Camellia assamica var. kucha, respectively. We previously demonstrated that the methylxanthine caffeine increased theacrine’s oral bioavailability in humans.
    [Show full text]
  • The Two Tonditionwinkturtin
    THETWO TONDITIONWINKTURTINUS 20170232103A1 ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2017/ 0232103 A1 Soane et al. (43 ) Pub. Date : Aug . 17, 2017 ( 54 ) EXCIPIENT COMPOUNDS FOR plication No . 62/ 245 , 513 , filed on Oct . 23, 2015 , BIOPOLYMER FORMULATIONS provisional application No . 62/ 245 ,513 , filed on Oct . (71 ) Applicant : ReForm Biologics , LLC , Cambridge , 23 , 2015 . MA (US ) Publication Classification (51 ) Int. Cl. (72 ) Inventors : David S . Soane , Palm Beach , FL (US ) ; A61K 39 /395 ( 2006 . 01 ) Philip Wuthrich , Belmont, MA (US ) ; A61K 47 / 12 (2006 . 01 ) Rosa Casado Portilla , Peabody , MA CO7K 16 /22 ( 2006 .01 ) (US ) ; Robert P . Mahoney , Newbury , A61K 47 /22 (2006 . 01 ) MA (US ) ; Mark Moody , Concord , MA CO7K 16 / 24 ( 2006 .01 ) (US ) ; Daniel G . Greene , Belmont , MA COZK 16 / 32 ( 2006 .01 ) (US ) (52 ) U . S . CI. CPC . .. A61K 39 / 39591 (2013 . 01 ) ; CO7K 16 / 241 ( 21) Appl . No. : 15 /331 , 197 ( 2013 . 01 ) ; CO7K 16 / 32 (2013 .01 ) ; CO7K 16 / 22 ( 2013 . 01 ) ; A61K 47/ 48215 ( 2013 .01 ) ; A61K (22 ) Filed : Oct . 21 , 2016 47 / 22 ( 2013 . 01 ) ; A61K 47 / 12 ( 2013 . 01) ; COZK 2317 /21 ( 2013 .01 ) ; CO7K 2317 /24 (2013 .01 ) Related U . S . Application Data ( 57 ) ABSTRACT (63 ) Continuation - in -part of application No . 14 / 966 ,549 , The invention encompasses formulations and methods for filed on Dec. 11 , 2015 , now Pat . No . 9 ,605 , 051 , which the production thereof that permit the delivery of concen is a continuation of application No . 14 /744 , 847 , filed trated protein solutions. The inventive methods can yield a on Jun .
    [Show full text]
  • ACUTE EFFECTS of THEACRINE SUPPLEMENTATION on MUSCULAR STRENGTH and MUSCULAR ENDURANCE Caleb J
    Southern Illinois University Carbondale OpenSIUC Research Papers Graduate School 2016 ACUTE EFFECTS OF THEACRINE SUPPLEMENTATION ON MUSCULAR STRENGTH AND MUSCULAR ENDURANCE Caleb J. Snyder [email protected] Follow this and additional works at: http://opensiuc.lib.siu.edu/gs_rp Recommended Citation Snyder, Caleb J. "ACUTE EFFECTS OF THEACRINE SUPPLEMENTATION ON MUSCULAR STRENGTH AND MUSCULAR ENDURANCE." (Jan 2016). This Article is brought to you for free and open access by the Graduate School at OpenSIUC. It has been accepted for inclusion in Research Papers by an authorized administrator of OpenSIUC. For more information, please contact [email protected]. ACUTE EFFECTS OF THEACRINE SUPPLEMENTATION ON MUSCULAR STRENGTH AND MUSCULAR ENDURANCE by Caleb J. Snyder B.S., Southern Illinois University, 2013 A Research Paper Submitted in Partial Fulfillment of the Requirements for the Master of Science in Education Department of Kinesiology in the Graduate School Southern Illinois University Carbondale May, 2016 RESEARCH PAPER APPROVAL ACUTE EFFECTS OF THEACRINE SUPPLEMENTATION ON MUSCULAR STRENGTH AND MUSCULAR ENDURANCE by Caleb J. Snyder B.S., Southern Illinois University, 2013 A Research Paper Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in Education in the field of Kinesiology Approved by: Motier D. Becque, Chair Graduate School Southern Illinois University Carbondale April 11th, 2016 AN ABSTRACT OF THE RESEARCH PAPER OF CALEB J. SNYDER, for the Master of Science in Education degree in KINESIOLOGY, presented on April 11, 2016, at Southern Illinois University Carbondale. TITLE: ACUTE EFFECTS OF THEACRINE SUPPLEMENTATION ON MUSCULAR STRENGTH AND MUSCULAR ENDURANCE MAJOR PROFESSOR: Dr. Motier D. Becque There are many performance-enhancing supplements on the market.
    [Show full text]