ADHD)-Like Behaviors in Spontaneously Hypertensive Rats

Total Page：16

File Type：pdf, Size：1020Kb

ADHD)-Like Behaviors in Spontaneously Hypertensive Rats

5,7-dihydroxy-6-methoxy-4'-phenoxyflavone, a derivative of oroxylin A improves attention- deficit/hyperactivity disorder (ADHD)-like behaviors in spontaneously hypertensive rats. Dela Peña IC, Young Yoon S, Kim Y, Park H, Man Kim K, Hoon Ryu J, Young Shin C, Hoon Cheong J. Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 139-742, Korea. Eur J Pharmacol. 2013 May 23. pii: S0014-2999(13)00378-6. doi: 10.1016/j.ejphar.2013.05.002. [Epub ahead of print] Oroxylin A, a major flavonoid in Scutellaria baicalensis, has been shown to alleviate attention- deficit/hyperactivity disorder (ADHD)-like behaviors in the Spontaneously Hypertensive rat (SHR) model of ADHD. As part of our continuing effort to discover effective ADHD drug candidates, we synthesized a number of oroxylin A derivatives and characterized their biological activities. Among all oroxylin A analogues, compound 7-7 (5,7-dihydroxy-6-methoxy-4'-phenoxyflavone) showed the most remarkable inhibition of dopamine reuptake alike methylphenidate, a dopamine transporter (DAT) blocker and typical drug for ADHD, and oroxylin A. It did not influence norepinephrine reuptake unlike atomoxetine, a selective norepinephrine inhibitor. Moreover, compound 7-7 reduced hyperactivity, sustained inattention and impulsivity in the SHR as measured by the open field, Y-maze and electro-foot shock aversive water drinking tests, respectively. Most drugs that enhance brain dopamine levels (e.g. DAT blockers like cocaine and methylphenidate) produce behavioral effects like those of stimulants causing them to be abused. However, the repeated treatment of compound 7-7 failed to elicit locomotor sensitization in rats, and neither produced conditioned place preference response nor maintained self-administration behavior. Altogether, the present study suggests the promising therapeutic value of compound 7-7as an ADHD drug. Furthermore, compound 7-7 may be considered as an alternative therapy to psychostimulant ADHD treatments (e.g. amphetamine and methylphenidate) for which use has been deemed controversial due to their abuse liability. 1.

Copy Link

Recommended publications

表 2.7.6.25－143 鉄剤の投与を受けた被験者の割合（Fas）（続き）
2.7.6 個々の試験のまとめ表 2.7.6.25－143 鉄剤の投与を受けた被験者の割合（FAS）（続き） 5.3.5.1―8 表 11.4.1―8 より引用 1282 Page 460 of 1887 2.7.6 個々の試験のまとめ (8) 血清フェリチン値 100 ng/mL 以上又は TSAT 20%以上の被験者の割合血清フェリチン値 100 ng/mL 以上又は TSAT 20%以上の被験者の割合を表 2.7.6.25－144 に示した．血清フェリチン値 100 ng/mL 以上又は TSAT 20%以上の被験者の割合は，全集団を対象に記載した．血清フェリチン値 100 ng/mL 以上又は TSAT 20%以上の被験者の割合は，MT-6548 群においてベースラインで 94.7%に対し，52 週後では 93.6%であり，darbepoetin 群においてベースラインで 90.8%に対し，52 週後では 96.7%であった． 1283 Page 461 of 1887 2.7.6 個々の試験のまとめ表 2.7.6.25－144 血清フェリチン値 100 ng/mL 以上又は TSAT 20%以上の被験者の割合（FAS） 5.3.5.1―8 表 14.2.3.8.1 より引用 1284 Page 462 of 1887 2.7.6 個々の試験のまとめ (9) 血球関連評価項目 MMRM を用いた MCV，MCH，ヘマトクリット，RBC，網状赤血球数及び網状赤血球率のベースラインからの変化量を表 2.7.6.25－145，表 2.7.6.25－146，表 2.7.6.25－147，表 2.7.6.25－148，表 2.7.6.25－149 及び表 2.7.6.25－150 に示した．血球関連評価項目は，全集団を対象に記載した． MMRM を用いた MCV の 52 週後のベースラインからの変化量の LSMean 及びその 95%CI は，MT-6548 群で 2.7 fL 及び 2.2～3.2 fL，darbepoetin 群で 0.1 fL 及び -0.3～0.6 fL であった．MMRM を用いた MCV の 52 週後のベースラインからの変化量の MT-6548 群と darbepoetin 群の差の LSMean 及びその 95%CI は，2.6 fL 及び 1.9～3.3 fL であり，統計学的に有意な差が認められた（p<0.001）. MMRM を用いた MCH の 52 週後のベースラインからの変化量の LSMean 及びその 95%CI は，MT-6548 群で 1.06 pg 及び 0.86～1.26 pg，darbepoetin 群で 0.01 pg 及び -0.19～ 0.20 pg であった．MMRM を用いた MCH の 52 週後のベースラインからの変化量の MT- 6548 群と darbepoetin 群の差の LSMean 及びその 95%CI は，1.05 pg 及び 0.77～1.34 pg であり，統計学的に有意な差が認められた（p<0.001）.
[Show full text]
TO COPE with Stress…
TO COPE WITH Stress ….. For the majority of the population life throws us unexpected curves, short or long lasting, in which we are forced to deal with and move on. This is an inevitable fact of life. Unfortunately, these stressors of life take their tole on our physiology, stripping us of some of our most precious resources...b vitamins. This is one of the reasons why sometimes after dealing with prolonged stress we feel like we just finished the Tour de France on foot. Interestingly, the nutraceutical universe does in fact provide a means to replenish these precious resources and at the same time, help ease the potential of flying off the handle when the stress volcano is on the verge of eruption. _____________________________________________________________________________ What do B Vitamins do? One of the major physiological damage pathways that stress initiates is activation of slight to moderate Our bodies have the amazing ability to convert sympathetic responses. This initiates the fight-or- macronutrients from food into usable potential and flight response and activation of the hypothalamic- kinetic energy through myriads of biochemical pituitary-adrenal axis, producing catecholamines and pathways. We know that these reactions are catalyzed cortisol, respectively. Catecholamine (adrenaline and by enzymes (globular proteins that speed up reaction noradrenaline) and corticosteroid secretion ultimately rates), but do enzymes have on/off switches? As ends up in glycogenolysis, lipolysis, proteinolysis, much as enzymes have the ability to speed up and activation of myriads of different biochemical reactions, most enzymes require coenzymes and pathways. As previously stated, the majority of the cofactors (small organic and inorganic molecules that enzymes involved in these pathways require b are required by enzymes to carry out their catalytic vitamins as coenzymes.
[Show full text]
Plant-Based Medicines for Anxiety Disorders, Part 2: a Review of Clinical Studies with Supporting Preclinical Evidence
CNS Drugs 2013; 24 (5) Review Article Running Header: Plant-Based Anxiolytic Psychopharmacology Plant-Based Medicines for Anxiety Disorders, Part 2: A Review of Clinical Studies with Supporting Preclinical Evidence Jerome Sarris,1,2 Erica McIntyre3 and David A. Camfield2 1 Department of Psychiatry, Faculty of Medicine, University of Melbourne, Richmond, VIC, Australia 2 The Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, VIC, Australia 3 School of Psychology, Charles Sturt University, Wagga Wagga, NSW, Australia Correspondence: Jerome Sarris, Department of Psychiatry and The Melbourne Clinic, University of Melbourne, 2 Salisbury Street, Richmond, VIC 3121, Australia. Email: [email protected], Acknowledgements Dr Jerome Sarris is funded by an Australian National Health & Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne, The Centre for Human Psychopharmacology at the Swinburne University of Technology. Jerome Sarris, Erica McIntyre and David A. Camfield have no conflicts of interest that are directly relevant to the content of this article. 1 Abstract Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations for anxiolytic activity.
[Show full text]
An in Silico Study of the Ligand Binding to Human Cytochrome P450 2D6
AN IN SILICO STUDY OF THE LIGAND BINDING TO HUMAN CYTOCHROME P450 2D6 Sui-Lin Mo (Doctor of Philosophy) Discipline of Chinese Medicine School of Health Sciences RMIT University, Victoria, Australia January 2011 i Declaration I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at RMIT university or any other educational institution, except where due acknowledgment is made in the thesis. Any contribution made to the research by others, with whom I have worked at RMIT university or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project‘s design and conception or in style, presentation and linguistic expression is acknowledged. PhD Candidate: Sui-Lin Mo Date: January 2011 ii Acknowledgements I would like to take this opportunity to express my gratitude to my supervisor, Professor Shu-Feng Zhou, for his excellent supervision. I thank him for his kindness, encouragement, patience, enthusiasm, ideas, and comments and for the opportunity that he has given me. I thank my co-supervisor, A/Prof. Chun-Guang Li, for his valuable support, suggestions, comments, which have contributed towards the success of this thesis. I express my great respect to Prof. Min Huang, Dean of School of Pharmaceutical Sciences at Sun Yat-sen University in P.R.China, for his valuable support.
[Show full text]
Application of Metabolomics in Viral Pneumonia
Lin et al. Chin Med (2019) 14:8 https://doi.org/10.1186/s13020-019-0229-x Chinese Medicine REVIEW Open Access Application of metabolomics in viral pneumonia treatment with traditional Chinese medicine Lili Lin1,2†, Hua Yan1,2†, Jiabin Chen3, Huihui Xie3, Linxiu Peng4, Tong Xie1,2, Xia Zhao1,2, Shouchuan Wang1,2 and Jinjun Shan1,2* Abstract Nowadays, traditional Chinese medicines (TCMs) have been reported to provide reliable therapies for viral pneumo- nia, but the therapeutic mechanism remains unknown. As a systemic approach, metabolomics provides an oppor- tunity to clarify the action mechanism of TCMs, TCM syndromes or after TCM treatment. This review aims to provide the metabolomics evidence available on TCM-based therapeutic measures against viral pneumonia. Metabolomics has been gradually applied to the efcacy evaluation of TCMs in treatment of viral pneumonia and the metabolomics analysis exhibits a systemic metabolic shift in lipid, amino acids, and energy metabolism. Currently, most studies of TCM in treatment of viral pneumonia are untargeted metabolomics and further validations on targeted metabolomics should be carried out together with molecular biology technologies. Keywords: TCM, Treatment, Metabolomics, Virus, Pneumonia Introduction etc. Te basic treatment principles are to regulate the Pneumonia is the world’s leading cause of death in young lung qi, resolve phlegm, and relieve cough and dyspnea. children and elderly people. Many pathogens are asso- Te TCM prescriptions is composed of various kinds of ciated with pneumonia, and now attention is turning medicinal plants, animals and minerals in the form of to the importance of viruses as pathogens [1]. In west- oral liquid, powder and granules.
[Show full text]
25-30 Herbs.Indd
Research American skullcap (Scutellaria laterifl ora): an ancient remedy for today’s anxiety? nxiety is ‘an unpleasant emotional state Abstract ranging from mild unease to intense fear’ Anxiety is a common but potentially serious disorder as it can lead to somatic and A(British Medical Association (BMA), 2002). social dysfunction. Orthodox anxiolytics are associated with unpleasant side-effects and Although anxiety is a normal response to stressful dependency. American skullcap (Scutellaria laterifl ora) is a popular herb in traditional situations it can be seen as a chronic manifestation medicine systems and the western materia medica for anxiety and related disorders. of a modern lifestyle that includes repeated daily Preliminary clinical and in vitro research provides encouraging support for its potential as a stressors (Pavlovich, 1999). It is a potentially serious safe, well-tolerated and effective alternative. disorder as it can precipitate a number of health problems and diffi culties in social and occupational functioning (Fricchione, 2004). Key points Physical symptoms of anxiety include pallor, Research has demonstrated the capacity of American skullcap’s fl avonoids to bind to sweating, hyperventilation, diarrhoea, irritable brain receptors implicated in modulation of anxiety bowel, fl ushing, dysphagia, palpitations, nausea, and In one year up to one in six UK adults in the UK may suffer from an unexplained muscle tension (BMA, 2002). Furthermore, Pitsavos psychological disorder, the most common being anxiety et al (2006) found strong evidence for a positive Anxiety and stress are common reasons for visits to herbal medicine practitioners association between severity of state anxiety in both An initial survey of UK and Ireland herbal medicine practitioners indicated American men and women and increased levels of plasma skullcap as their treatment of choice for anxiety and related disorders pro-infl ammatory cytokines, coagulation factors, Quality control of the raw herb and its commercial products is important.
[Show full text]
Scutellaria Baicalensis | Memorial Sloan Kettering Cancer Center
PATIENT & CAREGIVER EDUCATION Scutellaria baicalensis This information describes the common uses of Scutellaria baicalensis, how it works, and its possible side effects. Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe. How It Works Scutellaria baicalensis is used in traditional medicine to treat many medical conditions, but studies in humans are limited. S. baicalensis, also known as Huang Qin or Chinese skullcap, is a root extract used in traditional medicine. It is often used in combination with other herbs. Most studies have been done in the lab rather than in humans, and suggest anti-inflammatory and antioxidant activity. Some cancer cell lines undergo cell death when exposed to extracts of Scutellaria baicalensis 1/4 this herb, but some compounds in this herb may actually have opposite effects. Larger studies in humans that test safety and effectiveness are needed to determine under what circumstances S. baicalensis may be beneficial. Purported Uses To treat cancer Extracts from this herb cause cell death in some cancer cell lines, but human data are lacking. S. baicalensis has not been studied in clinical trials as a single agent, but has been studied in combination with other herbs in formulations such as PC- SPES and sho-saiko-to. To treat arthritis An herbal supplement containing S. baicalensis appeared to reduce symptoms of osteoarthritis. However, it is not known if the herb would exert similar effects by itself, and some supplements containing it have been associated with liver toxicity.
[Show full text]
Review Article Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy
Hindawi Publishing Corporation Neural Plasticity Volume 2016, Article ID 1320423, 18 pages http://dx.doi.org/10.1155/2016/1320423 Review Article Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy James Ahn,1 Hyung Seok Ahn,2 Jae Hoon Cheong,3 and Ike dela Peña1 1 Department of Pharmaceutical and Administrative Sciences, Loma Linda University, Loma Linda, CA 92350, USA 2School of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea 3Department of Pharmacy, Sahmyook University, Seoul 139-742, Republic of Korea Correspondence should be addressed to Ike dela Pena;˜ [email protected] Received 9 November 2015; Revised 30 December 2015; Accepted 10 January 2016 Academic Editor: Daniel Fung Copyright © 2016 James Ahn 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. Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD.
[Show full text]
Review Article Natural Compounds for the Management of Parkinson's
Hindawi BioMed Research International Volume 2018, Article ID 4067597, 12 pages https://doi.org/10.1155/2018/4067597 Review Article Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder Juan Carlos Corona Laboratory of Neurosciences, Hospital Infantil de Mexico´ Federico Gomez,´ Mexico Correspondence should be addressed to Juan Carlos Corona; [email protected] Received 28 June 2018; Revised 31 October 2018; Accepted 11 November 2018; Published 22 November 2018 Guest Editor: Francesco Facchiano Copyright © 2018 Juan Carlos Corona. Tis 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. Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unknown aetiology. Te pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, protein dysfunction, infammation, autophagy, apoptosis, and abnormal deposition of �-synuclein. Currently, the existing pharmacological treatments for PD cannot improve fundamentally the degenerative process of dopaminergic neurons and have numerous side efects. On the other hand, attention-defcit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and is characterised by hyperactivity, impulsiv- ity, and inattention. Te aetiology of ADHD remains unknown, although it has been suggested that its pathophysiology involves abnormalities in several brain regions, disturbances of the catecholaminergic pathway, and oxidative stress. Psychostimulants and nonpsychostimulants are the drugs prescribed for the treatment of ADHD; however, they have been associated with increased risk of substance use and have several side efects. Today, there are very few tools available to prevent or to counteract the progression of such neurological disorders.
[Show full text]
Molecular Mechanisms of Neuroprotection by an Alternative Drug Scutellaria Lateriflora by Madhukar Lohani a Dissertation Submitt
Molecular Mechanisms of Neuroprotection by an Alternative Drug Scutellaria lateriflora by Madhukar Lohani A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama August 02, 2014 Key words: American skullcap, Anxiety, Memory, Neuroprotection, Scutellaria lateriflora Copyright 2014 by Madhukar Lohani Approved by Barbara W Kemppainen, Chair, Professor of Anatomy, Physiology and Pharmacology Dean D Schwartz, Associate Professor of Anatomy, Physiology and Pharmacology Kellye Joiner, Associate Professor of Pathobiology Muralikrishnan Dhanasekaran, Associate Professor of Pharmacal sciences Frederik W Van Ginkel, Associate Professor of Pathobiology i Abstract Anxiety is one of the most prevalent neuropsychological disorders around the world. In the United States of America (USA), it is a serious health problem affecting a large number of people and is considered as one of the common disorder seen in the primary health care. Based on the current understanding of the pathologic mechanisms of anxiety, there are limited pharmacological and non-pharmacological therapies. Benzodiazepine (the current first line of therapy) has severe adverse effects such as anterograde amnesia, tolerance, psychomotor impairment, memory disruption, impaired psychomotor function, paradoxical anxiety or aggression, risks of accidents and even mortality. A double blind, placebo- controlled clinical trial indicated that commercial preparations of Scutellaria lateriflora have therapeutic benefits in anxiety with no evidence of toxicity. The purpose of this study was to examine the biological activities of S. lateriflora that may contribute to its neuroprotective mechanisms. The research study was conducted in four phases. The first two experimental approaches determined anti-oxidative potential and protective activities of S.
[Show full text]
Metabolic Enzyme/Protease
Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Metabolic Enzyme/Protease Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.
[Show full text]
The Effect of Supplementation with Scutellaria Baicalensis on Hepatic
Medical Hypotheses 133 (2019) 109402 Contents lists available at ScienceDirect Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy The effect of supplementation with Scutellaria baicalensis on hepatic function T ⁎ Basant K. Puria,b, , Nikita Whitec, Jean A. Monroc a C.A.R., Cambridge, UK b Hammersmith Hospital, London, UK c Breakspear Medical Group, Hemel Hempstead, Hertfordshire, UK ABSTRACT The dried root of the angiosperm Scutellaria baicalensis, also known as Chinese skullcap or Baikal skullcap, is widely used in traditional Chinese medicine, Korean traditional medicine and as a nutritional supplement; several studies have indicated that both the supplement and some of its ingredients may have clinically beneficial actions. However, the National Institutes of Health official guidance states that the use of Scutellaria “has been implicated in rare instances of clinically apparent liver injury” and that “the onset of symptoms and jaundice occurred within 6–24 weeks of starting skullcap, and the serum enzyme pattern was typically hepatocellular”, with marked increases in serum alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin levels. Careful perusal of all such published case reports showed that in each case the patient was concurrently taking at least one other supplement which had an established association with hepatic dysfunction. The authors hypothesised that long-term supplementation with Scutellaria baicalensis does not lead to hepatic dysfunction. The aim of this study was to test this hypothesis by assessing liver function before and after starting supplementation with Scutellaria baicalensis. Pre- and post-supplementation serum assays of alanine transaminase, aspartate transaminase, alkaline phosphatase and bilirubin were carried out in 17 patients (16 female) of average age 38.6 (standard error 4.4) years who had each taken 1335 mg dried root daily for an average of 444 (71) days.
[Show full text]