The document discusses the International Journal of Scientific and Innovative Research (IJSIR), a bi-annual journal published by Sky Institute in Lucknow, India. The journal aims to promote multidisciplinary research with societal benefit. The current issue contains 6 research papers covering various fields of science and technology. The editor thanks various individuals and organizations for their support and contributions to publishing the journal. He encourages continued support to help regularly publish quality issues of the journal.
International journal of scientific and innovative research 2013; 1(1)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
INTERNATIONAL JOURNAL OF SCIENTIFIC & INNOVATIVE RESEARCH (A Bi-annual Official Journal of Sky Institute, a constituent Institution of BALA JI FOUNDATION established under Societies Registration Act 1860). The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews
International journal of scientific and innovative research 2015; 3(2)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
International journal of scientific and innovative research 2015; 3(1)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
International journal of scientific and innovative research 2014; 2(2)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
International journal of scientific and innovative research 2013; 1(1)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
INTERNATIONAL JOURNAL OF SCIENTIFIC & INNOVATIVE RESEARCH (A Bi-annual Official Journal of Sky Institute, a constituent Institution of BALA JI FOUNDATION established under Societies Registration Act 1860). The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews
International journal of scientific and innovative research 2015; 3(2)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
International journal of scientific and innovative research 2015; 3(1)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
International journal of scientific and innovative research 2014; 2(2)p issn ...Sanjay Dixit
The International Journal of Scientific & Innovative Research (IJSIR) is a bi-annual published on line/ offline journal which publishes innovative research papers, reviews, mini reviews, short communications and notes dealing with all branches of science, technology, engineering health and agriculture. All manuscripts are subject to rapid peer review, those of high quality (not previously published and not under consideration for publication in another journal) contributing significantly to further the scientific knowledge in science, technology, engineering, health and agriculture will be published without delay. The subjects will cover all the disciplines and branches of science, technology, engineering, health and agriculture.
Demandas contra empresas extractivas presentadas en Canadá: Avances en el lit...Crónicas del despojo
Se han presentado ante tribunales canadienses un total de ocho demandas sobre abusos ambientales o a los derechos humanos en relación a las operaciones de empresas extractivas canadienses en el exterior. Si bien ninguna de las partes demandantes extranjeras ha tenido éxito hasta la fecha en un litigio de este tipo, existen cinco casos interpuestos por demandantes extranjeros ante los tribunales canadienses.
Informe Anual SIADDHH 2015 sobre Agresiones contra Defensores de Derechos Hum...Crónicas del despojo
Se cumplen 5 años del Gobierno Santos y la situación de protección y garantías a los defensores y defensoras, lejos de mejorar, preocupa. En 2015 repuntan nuevamente las cifras de agresiones muy a pesar de la sensible baja en la violencia sociopolítica producto del cese unilateral del fuego de las FARC y el desescalamiento del conflicto. Si esto es ahora ¿qué se puede esperar del post-conflicto? Situación de defensores en 2015 es tan inverosímil que parece más una película, que la realidad. Escrito por Comunicaciones (CJL) - Corporación Jurídica Libertad
Inflammatory Bowel Disease (IBD) is a multifactorial disorder with many different putative influences mediating disease onset, severity, progression and diminution. Spontaneous natural IBD is classically expressed as Crohn’s Disease (CD) and Ulcerative Colitis (UC) commonly found in primates; lymphoplasmocytic enteritis, eosinophilic gastritis and colitis, and ulcerative colitis with neuronal hyperplasia in dogs; and colitis in horses. Spontaneous inflammatory bowel disease has been noted in a
number of rodent models which differ in genetic strain background, induced mutation, microbiota influences and immunopathogenic pathways. Histological lesions in Crohn’s Disease feature noncaseating granulomatous inflammation while UC lesions typically exhibit ulceration, lamina propria inflammatory infiltrates and lack of granuloma development. Intestinal inflammation caused by CD and UC is also associated with increased incidence of intestinal neoplasia. Transgenic murine models have determined underlying etiological influences and appropriate therapeutic targets in IBD. This literature review will discuss current opinion and findings in spontaneous IBD, highlight selected transgenic rodent models of IBD and discuss their respective pathogenic mechanisms. It is very important to provide accommodation of induced putative deficits in activities of daily living and to assess discomfort and pain levels in the face of significant morbidity and/or mortality in these models. Epigenetic, environmental
(microbiome, metabolome) and nutritional factors are important in IBD pathogenesis, and evaluating ways in which they influence disease expression represent potential investigative approaches with the greatest potential for new discoveries.
La extracción de materias primas para aumentar las exportaciones según la demanda a nivel mundial de los países netamente industrializados y de primer orden, afectan en gran medida las condiciones sociales y económicas de las poblaciones donde se realiza esta nefasta práctica, es decir, en los sectores subalternos de los países periféricos donde el neoliberalismo extremo, la economía transnacionalizada acompañada de la violencia para-institucional son protagonistas en la realidad nacional de dichos territorios.
International Journal of Life-Sciences Scientific Research (www.ijlssr.com) is a bi-monthly published online, which publishes innovative research papers related Biotechnology, Genetics, Molecular biology, Immunology, Microbiology, Biochemistry, Bioinformatics, Pharmaceutical Sciences, Cell Biology, Veterinary sciences, Biostatistics, Chemistry, Botany, Zoology, Environmental sciences, Nanosciences & Nanotechnology, Agricultural sciences, Medical Sciences, and other allied science fields. The Journal welcomes the original research articles, reviews, mini-reviews, short communications and notes.
IJLSSR is a board ranging open access journal. It gives full text availability of articles in PDF format only. With the facility of fast online manuscript submission and Email alert updates we gives rapid publication and high visibility. We started with a Mission to encourage contribution to Research in Sciences and Technology for achieving better future lives for all. We serve science and mankind at the highest levels of professional Ethical Conduct.
Article 9 A STUDY ON GREEN FINANCING PATTERN IN THE BANKING SECTOR ACASE STUD...Dr UMA K
Reference: Dr. Uma. K (2021) “A STUDY ON GREEN FINANCING PATTERN IN THE BANKING SECTOR: A CASE STUDY OF ORGANIC FARMERS IN MANDYA DISTRICT”, International Journal of Advance and Innovative Research (Conference Special), (IJAIR), www.iaraedu.com, ISSN: 2394-7780, Impact factor 7.363, Volume 8, Issue 3 (II), Page No 19 – 26.
Demandas contra empresas extractivas presentadas en Canadá: Avances en el lit...Crónicas del despojo
Se han presentado ante tribunales canadienses un total de ocho demandas sobre abusos ambientales o a los derechos humanos en relación a las operaciones de empresas extractivas canadienses en el exterior. Si bien ninguna de las partes demandantes extranjeras ha tenido éxito hasta la fecha en un litigio de este tipo, existen cinco casos interpuestos por demandantes extranjeros ante los tribunales canadienses.
Informe Anual SIADDHH 2015 sobre Agresiones contra Defensores de Derechos Hum...Crónicas del despojo
Se cumplen 5 años del Gobierno Santos y la situación de protección y garantías a los defensores y defensoras, lejos de mejorar, preocupa. En 2015 repuntan nuevamente las cifras de agresiones muy a pesar de la sensible baja en la violencia sociopolítica producto del cese unilateral del fuego de las FARC y el desescalamiento del conflicto. Si esto es ahora ¿qué se puede esperar del post-conflicto? Situación de defensores en 2015 es tan inverosímil que parece más una película, que la realidad. Escrito por Comunicaciones (CJL) - Corporación Jurídica Libertad
Inflammatory Bowel Disease (IBD) is a multifactorial disorder with many different putative influences mediating disease onset, severity, progression and diminution. Spontaneous natural IBD is classically expressed as Crohn’s Disease (CD) and Ulcerative Colitis (UC) commonly found in primates; lymphoplasmocytic enteritis, eosinophilic gastritis and colitis, and ulcerative colitis with neuronal hyperplasia in dogs; and colitis in horses. Spontaneous inflammatory bowel disease has been noted in a
number of rodent models which differ in genetic strain background, induced mutation, microbiota influences and immunopathogenic pathways. Histological lesions in Crohn’s Disease feature noncaseating granulomatous inflammation while UC lesions typically exhibit ulceration, lamina propria inflammatory infiltrates and lack of granuloma development. Intestinal inflammation caused by CD and UC is also associated with increased incidence of intestinal neoplasia. Transgenic murine models have determined underlying etiological influences and appropriate therapeutic targets in IBD. This literature review will discuss current opinion and findings in spontaneous IBD, highlight selected transgenic rodent models of IBD and discuss their respective pathogenic mechanisms. It is very important to provide accommodation of induced putative deficits in activities of daily living and to assess discomfort and pain levels in the face of significant morbidity and/or mortality in these models. Epigenetic, environmental
(microbiome, metabolome) and nutritional factors are important in IBD pathogenesis, and evaluating ways in which they influence disease expression represent potential investigative approaches with the greatest potential for new discoveries.
La extracción de materias primas para aumentar las exportaciones según la demanda a nivel mundial de los países netamente industrializados y de primer orden, afectan en gran medida las condiciones sociales y económicas de las poblaciones donde se realiza esta nefasta práctica, es decir, en los sectores subalternos de los países periféricos donde el neoliberalismo extremo, la economía transnacionalizada acompañada de la violencia para-institucional son protagonistas en la realidad nacional de dichos territorios.
International Journal of Life-Sciences Scientific Research (www.ijlssr.com) is a bi-monthly published online, which publishes innovative research papers related Biotechnology, Genetics, Molecular biology, Immunology, Microbiology, Biochemistry, Bioinformatics, Pharmaceutical Sciences, Cell Biology, Veterinary sciences, Biostatistics, Chemistry, Botany, Zoology, Environmental sciences, Nanosciences & Nanotechnology, Agricultural sciences, Medical Sciences, and other allied science fields. The Journal welcomes the original research articles, reviews, mini-reviews, short communications and notes.
IJLSSR is a board ranging open access journal. It gives full text availability of articles in PDF format only. With the facility of fast online manuscript submission and Email alert updates we gives rapid publication and high visibility. We started with a Mission to encourage contribution to Research in Sciences and Technology for achieving better future lives for all. We serve science and mankind at the highest levels of professional Ethical Conduct.
Article 9 A STUDY ON GREEN FINANCING PATTERN IN THE BANKING SECTOR ACASE STUD...Dr UMA K
Reference: Dr. Uma. K (2021) “A STUDY ON GREEN FINANCING PATTERN IN THE BANKING SECTOR: A CASE STUDY OF ORGANIC FARMERS IN MANDYA DISTRICT”, International Journal of Advance and Innovative Research (Conference Special), (IJAIR), www.iaraedu.com, ISSN: 2394-7780, Impact factor 7.363, Volume 8, Issue 3 (II), Page No 19 – 26.
International Journal Of Aquaticscience And Technology : Issn 2320-6772J.P.M. Institute
INTERNATIONAL JOURNAL OF AQUATIC SCIENCE AND TECHNOLOGY is a biannual an academic and peer-reviewed
Journal published by ACADEMIC AND RESEARCH PUBLICATIONS in Collaboration with JPMS Society.
JPMS Societyis a Society registered under the Societies Registration Act and its Registration No. is 1649/1986-87. It was published from year i.e. 2013. The ISSN No. of the JOURNAL is - 2320-6772 .
Dr.Rahul Hajare is a post doctoral student of Renowned Scientist Respected Dr. R S. Paranjape Retired Director and Scientist ‘G’ National AIDS Research Institute India. He achieved his training at the National AIDS Research Institute, the reputed and primer HIV research institute in India. Dr. Hajare is board certified by Director-in-Charge, National AIDS Research Institute, the Secretory Board of Management KLE Society Belagavi, Registrar Vinayaka Mission’s Research Foundation, Aarti Drugs Limited and Shikshan Vikas Mandal. Dr Hajare won World Academic Championship-2017 in Pharmacy (Antiretroviral Therapy) and certified as Fellow, Directorate of Pharmacy, IASR (Lifetime Membership).
International Journal of Agricultural Science and Technology (IJAgST) vol 3 ...J.P.M. Institute
INTERNATIONAL JOURNAL OF AGRICULTURAL SCIENCE AND TECHNOLOGY is a biannual an academic
and peer-reviewed Journal published by ACADEMIC AND RESEARCH PUBLICATIONS. It was published from year i.e.2012. The ISSN of the JOURNAL is 2319-880X.
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Society of Nepalese Students in Korea ( SONSIK) is organizing a Academic event on Feb. 16th, 2014.:
Please have a look. Your views are very important and we welcome your feedback which will help us success the event.
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June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
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The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
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This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
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• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
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2. Editorial
I am happy to convey that second issue of third volume of "International Journal of Scientific and
Innovative Research (IJSIR)", a bi-annual journal has been published by Sky Institute, Lucknow in an
effort to promote multidisciplinary scientific and innovative research of societal benefit. This journal
covers all branches of science, technology, engineering, health, agriculture and management.
Research articles in the field of education are also encouraged in order to promote educational
technology aiming at improvement in present educational system.As research and development (R &
D) has been playing a significant role in overall development of society, continuous multidisciplinary
innovative research in science and technology is needed to address the challenges in context to
changing environmental conditions in the present era of gradual increase in industrial and
technological advancement at global level. Efforts should be made to develop eco-friendly
technologies in order to provide solutions for developing socially, economically and culturally
sustainablesociety.
The present issue of International Journal of Scientific and Innovative Research (IJSIR) contains 6
research papers I articles covering different areas of science and technology.All these papers are well
written and informative in content. I express my sincere thanks and gratefulness to Mr.Mohit Bajpai,
Chairman, Sky Institute, Lucknow (U.P.), India for his support in publishing it. I express my thanks to
members of Committee for Editorial Assistance Dr. B.C.Tripathi, Dr. Pankaj Verma, Shri Sanjay
Pandey, Shri Sanjay Dixit and Mr. Shamshul Hasan Khan for their hard work and devotion in giving
the final shape to the journal. I am thankful to all faculty members, scientists and research scholars of
different universities, research organizations and technical institutions for contributing their research
articles for publication in the present issue of the journal. The help provided by faculty members and
supporting staff of Sky Institute in publishing the present volume of the journal is also acknowledged. I
hope scientists, academicians and young researchers will be greatly benefited by this publication for
theirresearchwork.
I request humbly to the readers and contributors of our journal to continue encouraging us for regular
publication of the journal. Any suggestion and comment for the improvement in the quality of the
journalarealwayswelcome.
Dr. B. R. Pandey
Editor-in-Chief
3. International Journal of Scientific and Innovative Research 2014; 2(1): 281-285,
P-ISSN 2347-2189, E- ISSN 2347-4971
www.ijsir.co.in 295
DR. B.R. PANDEY
DIRECTOR (RESEARCH)
SKY INSTITUTE, KURSI ROAD, LUCKNOW, U.P, INDIA
FORMER JOINT DIRECTOR, COUNCIL OF SCIENCE & TECHNOLOGY, UP, LUCKNOW
(DEPARTMENT OF SCIENCE AND TECHNOLOGY, UP GOVERNMENT), INDIA
FORMER PROFESSOR, INTERNATIONAL INSTITUTE OF HERBAL MEDICINE (IIHM), LUCKNOW, U.P., INDIA
E-MAIL ID: editorijsir02@gmail.com, MOBILE-: 9794849800
Dr. B.C.Tripathi
Assistant Prof.
Deptt. of Education,
Rama P.G. College,
Chinhat, Lucknow,
Uttar Pradesh
Dr. Pankaj Verma
Senior Research Fellow,
Deptt. of Oral & Maxillofacial Surgery,
Faculty of Dental Sciences,
K.G. Medical University,
Lucknow, Uttar Pradesh
Shri Sanjay Pandey
Assistant Prof.
National Institute of
Fashion Technology,
Raebareli,
Uttar Pradesh
Shri Ashish Tiwari
Research Scholar,
Sai Nath University,
Ranchi,
Jharkhand
ADVISORY BOARD
EDITOR-IN-CHIEF
COMMITTEE FOR EDITORIAL ASSISTANCE
Prof.(Dr.)S. P. Ojha
Former Vice Chancellor, CCS Meerut University, Meerut, Uttar Pradesh
Prof.(Dr.)V.K. Srivastava
Former Prof & Head, Deptt. of Community Medicine
King George Medical University, Lucknow.
Former Director, Integral Institute of Medical Sciences & Research,
Integral University, Lucknow
Former Vice -Chancellor,
Texila American University, Georgetown, Guyana, South America
Prof.(Dr.) M.I. Khan
Prof & Head, Deptt. of Mechanical Engg.,
Integral University, Lucknow, Uttar Pradesh
Prof. (Dr.) S.K. Avasthi
Former Director, H.B.T.I., Kanpur, Uttar Pradesh
Prof.(Dr.) Amrika Singh
Prof & Head (Chemistry), Deptt. of Applied Sciences,
Institute of Engg. & Technology, Sitapur Road, Lucknow, Uttar Pradesh
Prof.(Dr.) U.N. Dwivedi
Prof & Ex- Head, Deptt of Biochemistry, Former Pro- Vice Chancellor,
Former Dean, Faculty of Science, University of Lucknow, Lucknow, U.P.
Prof.(Dr.) U.K. Misra
Head, Deptt. of Neurology, Ex Dean,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, U.P.
Dr. A.K. Gupta
Former Deputy Director General,
Indian Council of Medical Research (ICMR), Ansari Nagar, New Delhi
Prof.(Dr.) V.K.Tondon
Former Prof & Head, Deptt. of Chemistry, Ex- Dean Faculty of Science,
University of Lucknow, Lucknow, Uttar Pradesh
Prof. (Dr.) Amod Kumar Tiwari,
Prof.- Director, Bhabha Institute of Engg.& Technology, Kanpur, U.P.
Prof.(Dr.) Chandra Dhar Dwivedi
Former Prof. & Chairman, Deptt. of Pharmaceutical Sciences, College of
Pharmacy, South Dakota State University, Borokings, South Dakota, USA
Prof.(Dr.) Vimal Kishore
Prof. & Chairman, Deptt. of Basic Pharmaceutical Sciences,
Xevier College of Pharmacy, University of Louisiana, 7325,
Palmetto Street New Orlens, Louisiana USA
Prof .(Dr.) M.C. Pant,
Former Director,
R. M. L. Institute of Medical Sciences, Lucknow and Prof. & Head,
Deptt. of Radiotherapy, K. G. Medical University, Lucknow, Uttar Pradesh
Prof. (Dr.) S.P. Singh
Former Prof & Head, Deptt. of Pharmacology,
G. S. V. M. Medical College, Kanpur, Uttar Pradesh
Prof. (Dr.) R. L. Singh
Prof & Head, Department of Biochemistry & Coordinator Biotechnology
Program , Dr. R. M. L. University Faizabad, Uttar Pradesh
Dr. Sarita Verma
Head, Deptt. of Home Sci., Mahila P.G. College, Kanpur, Uttar Pradesh
Prof. (Dr.) S.K.Agarwal
Pro. & Ex-Head, Deptt. of Biochemistry, Lucknow University, Lucknow, U.P.
Dr. Bharat Sah
Director,
National Institute of Fashion Technology, Raebareli, Uttar Pradesh
Prof.(Dr.)N.S. Verma
Prof., Deptt. of Physiology,
K. G. Medical University, Lucknow, Uttar Pradesh
Prof.(Dr.)A.K. Tripathi
Prof. & Head, Deptt. of Clinical Hematology & Medical Oncology,
K. G. Medical University, Lucknow, Uttar Pradesh
Prof.(Dr.)C.M. Pandey
Prof. & Head, Deptt. of Biostatistics & Health Informatics,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow,
Uttar Pradesh
Dr. Rupesh Chaturvedi
Associate Prof., School of Biotechnology,
Jawaharlal Nehru University, New Delhi, Former Asstt. Prof., Deptt. of
Pharmaceutical Sciences , College of Pharmacy, Vanderbilt University,
Tennessee, USA
Dr. S.Sinha
Asstt. Prof. Deptt. of Internal Medicine, CD University,
C. David Giffen School of Medi., University of California, Los Angeles, USA
Dr. K.Raman
Principal Scientist, Martek Biosciences Corporation,
6480 Dobbin Road, Columbia, MD 21045, USA
Dr. P.K.Agarwal
Editor –in – Chief, Natural Product Communication,
Natural Product Inc 7963, Anderson Park Lane West Terville, OH, USA
Dr. R.K.Singh,
Chief Scientist, Division of Toxicology, CSIR-Central Drug Research
Institute, Jankipuram Extension, Lucknow, Uttar Pradesh
Dr. Mohd. Tarique
Prof., Deptt of Physical Edu., Lucknow University, Lucknow, Uttar Pradesh
1
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EDITORIAL BOARD
Prof.(Dr.) Y.B. Tripathi
Prof. & Head, Deptt. of Medicinal Chemistry,Institute of Medical Sciences,
Banaras Hindu University Varanasi, Uttar Pradesh
Prof.(Dr.) R.K. Singh
Prof. & Head , Deptt. of Biochemistry, Shri Guru Ram RaiInstitute of Medical
& Health Sciences, Dehradun, Uttarakhand & Former Prof. & Head,
Department of Biochemistry, K. G. Medical University , Lucknow, U.P.
Prof. (Dr.) R.S.Diwedi
Former Director, National Research Centre for Groundnut (NRCG) , ICAR,
Junagarh, Gujarat & Former Principal Scientist – Head, Deptt. of Plant
Physiology, Indian Institute of Sugarcane Research, Lucknow, Uttar Pradesh
Prof. (Dr.) Nuzhat Husain
Prof. & Head , Deptt of Pathology & Acting Director, R. M. L. Institute of
Medical Sciences, Lucknow,Uttar Pradesh
Prof. (Dr.) Amita Jain
Prof. Deptt. of Microbiology, K.G. Medical University, Lucknow, U.P.
Dr. Sudhir Mahrotra
Associate Prof., Deptt. of Biochemistry, Lucknow University, Lucknow, U.P.
Prof. (Dr.) Vibha Singh
Prof., Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental Sciences,
K. G. Medical University, Lucknow, Uttar Pradesh
Prof. (Dr.) U.S. Pal
Prof. & Head, Deptt. of Oral & Maxillofacial Surgery, Faculty of Dental
Sciences, K. G. Medical University, Lucknow, Uttar Pradesh
Prof. (Dr. ) K.K. Pant
Prof. & Head , Deptt. of Pharmacology & Therapeutics,
K. G. Medical University, Lucknow, Uttar Pradesh
Dr. C.M.K.Tripathi
Former Deputy Director & Head, Division of Fermentation Technology, CSIR-
Central Drug Research Institute , Lucknow, Uttar Pradesh
Dr. R.D. Tripathi
Chief Scientist & ProfessorPlant Ecology & Environmental Science Division,
Uttar Pradesh CSIR-National Botanical Research Institute, Lucknow, U.P.
Prof.(Dr.) Ashwani K. Srivastav
Prof. & Head, Deptt. of Biosciences, Integral University,Lucknow,
Former Senior Scientist, Birbal Sbahani Institute Paleobotany, Lucknow, U.P.
Prof.(Dr.) L. Pandey
Prof. & Head , Postgraduate Deptt . of Physics,Former Dean, Faculty of
Science, Rani Durgawati University, Jabalpur, Madhya Pradesh, India
Prof .(Dr.) Bali Ram
Prof., Deptt. of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh
Prof.(Dr.) J.P.N.Rai
Prof.& Head, Deptt. of Environmental Sciences, G.B. Pant University of Agr. &
Technology, Pant Nagar, Uttarakhand
Prof.(Dr. )R. S. Dubey
Prof. & Head, Deptt. of Biochemistry, Banaras Hindu University, Varanasi, U.P.
Prof. (Dr.) Omkar
Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) Sudhir Kumar
Prof., Deptt. of Zoology, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) Naveen Khare
Prof., Deptt. of Chemistry, Lucknow University, Lucknow, Uttar Pradesh
Prof.(Dr.) S. M. Natu
Prof., Deptt. of Pathalogy,K.G. Medical University, Lucknow, Uttar Pradesh
Dr. Kusum Lata Mishra,
In-charge, Coagulation Laboratory, Deptt. of Pathology,
K.G. Medical University, Lucknow, Uttar Pradesh
Prof.(Dr.)V.K. Sharma,
Prof., Deptt. of Chemistry, Lucknow University, Uttar Pradesh
Prof.(Dr.) R.K. Shukla
Prof., Deptt. of Physics, Lucknow University, Lucknow Uttar Pradesh
Prof.(Dr.)Anil Gaur
Prof., Deptt. of Biotechnology & Genetic Engg., G.B. Pant University of Agr.
& Technology, Pant Nagar, Uttarakhand
Dr. Mahesh Pal
Principal Scientist ,Phytochemistry Division, CSIR- National Botanical
Research Institute, Lucknow, Uttar Pradesh
Dr. Vinod Singh
Assoc. Prof. & Head, Deptt. of Microbiology, Baruktulla University, Bhopal,
Madhya Pradesh
Dr. K.K.Verma
Assoc. Prof., Deptt. of Physics & Electronics.Dr. R. M. L. Awadh University ,
Faizabad,Uttar Pradesh
Dr. Atul Gupta
Senior Scientist, CSIR- Central Institute of Medicinal & Aromatic Plants,
Lucknow, Uttar Pradesh
Dr. Saudan Singh,
Senior Principal Scientist,CSIR- Central Institute of Medicinal & Aromatic
Plants , Lucknow, Uttar Pradesh
Dr. S.K.Tiwari
Senior Principal Scientist ,CSIR- National Botanical Research Institute,
Lucknow, Uttar Pradesh
Dr. Shivani Pandey,
Asstt. Prof., Deptt. of Biochemistry,K.G.Medical University, Lucknow, U.P.
Dr. B.C. Yadav,
Lucknow Associate Prof. & Coordinator, Deptt. of Applied Physics, School for
Physical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, U.P.
Dr. Anchal Srivastava,
Prof., Deptt of Physics, Lucknow University,Lucknow, Uttar Pradesh
Dr. Shalini Bariar
Asstt. Professor, Durga Devi Saraf Institute of Management, Mumbai, India
Dr.A.K.Pandey
Principal Scientist, National Bureau of Fish Genetic Resources,Lucknow, U.P.
Dr.S.K.Pandey
G.M. LML Factory, Kanpur Uttar Pradesh
Dr. Suneet Kumar Awasthi,
Asst. Prof ,Deptt.of PhysicsJ.P. University, Noida, Uttar Pradesh
Dr.G. N. Pandey
Asst. Prof, Deptt. of Physics Amity University, Noida ,Uttar Pradesh
Dr. Mukesh Verma
Asst. Prof., Deptt. of Physical Education, Dr. R.M.L. Avadh University,
Faizabad, Uttar Pradesh
Dr. Abhay Singh,
Head, Physical Education, Delhi Public School, Lucknow Uttar Pradesh
Dr. Santosh Gaur
Asst. Prof. Deptt. of Physical Education, Jawahar Lal Nehru P.G. College,
Barabanki, Uttar Pradesh
Dr.Sanjeev Kumar Jha
Senior Scientist, DEOACC Patna
Dr. Shivlok Singh
Scientist, DEOACC, Lucknow, Uttar Pradesh
Dr. Anurag Tripathi,
Asstt . Prof. , Deptt. of Electrical Engg., Institute of Engg. & Technology,
Sitapur Road, Lucknow, Uttar Pradesh
Prof. V.P.Sharma
Senior Principal Scientist, CSIR-Indian Institute of Toxicology Research,
Lucknow, Uttar Pradesh
Dr. Krishna Gopal
Former Deputy Director & Head , Aquatic Toxicology Division, CSIR- Indian
Institute of Toxicology Research, Lucknow, Uttar Pradesh
Dr. S.P. Shukla
Prof. , Deptt. of Civil Engg., Institute of Engg. & Technology, Sitapur Road ,
Lucknow, Uttar Pradesh
Dr. Ajay Mishra
Associate Prof. , Deptt. of Geology, Lucknow University, Lucknow , U. P.
Dr. Ashutosh Singh
Prof., Deptt. of Chemistry,Saket P.G. College, Ayodhya, Faizabad, U. P.
Dr. S.K. Singh
Principal, Gita College of Education , Nimbari, Panipat, Haryana
Shri Sudesh Bhat
Advisor (Education), Sky Institute, Lucknow, Uttar Pradesh
Dr. Krishna Gopal
Asst. Prof., Deptt. of English,Rama University, Kanpur, Uttar Pradesh
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ABOUT EDITOR-IN- CHIEF : DR. B. R. PANDEY
Dr. B. R. Pandey is a well known academician and scientist with brilliant academic career and
research accomplishments . He has done M.Sc. ( organic chemistry) from Banaras Hindu University,
Varanasi, India in the year 1972. He has done PhD in Medicinal Chemistry under the guidance of world
renowned Biochemist & Medicinal Chemist, Professor S.S. Parmar , Professor of Medicinal Chemistry &
Chemical Pharmacology, Department of Pharmacology & Therapeutics, K. G. Medical College, Lucknow
( Presently K. G. Medical University), Faculty of Medicine, University of Lucknow, Lucknow, India in the
year 1976. Dr. Pandey has all throughout first class educational qualifications and his research interest
covers medicinal chemistry, biochemical pharmacology, neurochemistry, neuro-toxicology, environmental
chemistry, herbal medicine & natural products. He is having extensive research experience of more than 40
years and published several research papers in peer reviewed journals of international repute. His research
particularly on the studies of central nervous system acting drugs and anti-inflammatory drugs and their
biochemical mode of action using animal models and enzymes such as monoamine oxidase, acetylcholine
esterase, purine catabolizing enzymes , proteolytic enzymes, membrane stabilizing enzymes, respiratory
enzymes, microsomal enzymes etc. has been well recognized as evidenced by his research publications .
Further, his research on developing herbal medicines has been found very useful in prevention and treatment
of chronic diseases and other refractory diseases for which modern system of medicine have no permanent
cure. He has worked on the position of Joint Director, Council of Science & Technology, U.P., Lucknow,
Department of Science & Technology, Uttar Pradesh Government, India from the year 1979 to 2011, where
he successfully executed several R & D projects in various disciplines of Science & Technology including
chemical & pharmaceutical sciences, medical sciences, biological sciences, environmental sciences etc.
During his tenure as Joint Director, he has been instrumental in launching and implementing important
schemes: Young Scientists Scheme, Young Scientist Visiting Fellowship Scheme, Establishment of Centre
of Excellence- Encephalitis Research Centre of Excellence in Sanjay Gandhi Post Graduate Institute of
Medical Sciences ( SGPGIMS), Lucknow , U. P. India ; Centre of Excellence in Materials Science ( nano
materials) in Z. H. College of Engg. & Technology, Aligarh Muslim University, Aligarh, U.P. India,
Establishment of Patent Information Centre in the premises of Council of Science & Technology , U.P. He
has also worked on the post of Secretary ( as additional charge ) , Council of Science & Technology, U.P.
several times and functioned as Administrative Head of the Organization. Prior to taking over the position
of Joint Director, Council of Science & Technology, U.P. in the year 1979, he has worked as Junior Research
Fellow/ Senior Research Fellow ( Council of Scientific & Industrial Research, New Delhi ), Assistant
Research Officer ( Jawaharlal Nehru Laboratory of Molecular Biology) at Department of Pharmacology
&Therapeutics, K. G. Medical College ( presently K. G. Medical University), Faculty of Medicine, University
of Lucknow, Lucknow, India from the year 1972 to 1979 and involved in multidisciplinary biomedical
research leading to drug development . He has worked as Visiting Scientist / Faculty in the Department of
Physiology, School of Medicine, University of North Dakota, Grand Forks, North Dakota, USA and also
visited scientific institutions in Sweden, U.K. and U.S.A. under Training Program on Capacity Building in
Environmental Research Management (World Bank Funding Project). After his superannuation in the year
2011, he has been associated with International Institute of Herbal Medicine (IIHM), Lucknow, India as
Professor and is presently associated with Sky Institute, Lucknow , India as Director ( Research) and
involved in programs related to higher education and research of scientific & technological fields. He has
3
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International Journal of Scientific and Innovative Research 2014; 2(1): 281-285,
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organized several national and international conferences. He has actively participated in national and
international conferences, symposia and workshops and presented research papers and chaired scientific /
technical sessions. He is life member and fellow of many scientific societies such as National Academy of
Sciences India , Society of Toxicology of India, Indian Academy of Neurosciences, Bioved Research
Society India, International Society for Herbal Medicine (ISHM), Society of Biological Sciences and Rural
Development, India. He has been member of several scientific expert committees/ advisory committees to
evaluate scientific research proposals. Dr. Pandey has been actively associated with various universities
and institutions in India as examiner for conducting graduate, post graduate and doctoral level examinations
in disciplines like chemical sciences, pharmaceutical sciences, biochemical sciences, biotechnology and
allied areas and member of Board of Studies for the academic development in the department. He has been
approved research supervisor for guiding research in chemistry, biotechnology and related areas from various
universities of India leading to PhD Degree. In view of his vast research and administrative experience and
broad R & D vision, Dr. Pandey has been associated with International Journal of Scientific & Innovative
Research (IJSIR) as Editor-in-Chief.
4
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FROM THE DESK OF CHAIRMAN, SKY INSTITUTE
It is my privilege to state that I have great desire to contribute to the
development of our country and to bring about social transformation through
education, higher learning and research. This inner feeling prompted me to
establish Sky Institute in Lucknow (Uttar Pradesh), the city known for its rich
cultural heritage and vibrant academic institutions of higher learning. Sky
Institute, since its inception in the year 2006, has been functioning to impart
various educational and training courses with a vision to improving lives
through education, research and innovation. The institute provides a professional learning
environment that acts as a catalyst, for the exponential growth of student as well as extracurricular
abilities. It conducts regular courses as well as distance learning courses at the level of under graduate
and post graduate followed by research courses leading to M Phil and PhD in all subjects in association
with universities recognized by University Grants Commission (UGC), the Distance Education
Council (DEC),Association of Indian Universities (AIU), Ministry of Human Resource Development
(MHRD), Government of India.
I feel great pleasure to highlight that Sky Institute has started to publish a bi-annual journal
“International Journal of Scientific and Innovative Research (IJSIR)” which encourages to publish
research articles in all branches of science, technology ,engineering, health, agriculture and
management. Research articles in the field of education are also considered in order to improve
educational standard in educational institutions with innovative technologies. First volume of the
journal has been successfully published. The present issue of second volume of the journal contains
useful and informative research articles which may be interesting to readers and educational and
research organizations. The association of eminent faculty and scientists of reputed organizations
with our journal is highly appreciable.
I call upon all the students who are willing to join various programs/courses being run at Sky
Institute in association with selected universities, to strive hard to gain knowledge, transform it into
skills with right attitude and inculcate the habit of learning, which will drive them to self directed
learning.
My best wishes to all the aspiring students.
Mohit Bajpai
Chairman
Sky Institute
5
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CONTENTS PAGE
SIGNIFICANCE OF ASCORBATE IN TRANS-PLASMA MEMBRANE ELECTRON 1
TRANSPORT IN HEALTH AND DISEASE OF HUMANS: REVIEW
Varsha Shukla, Babita Singh, A.A.Mahdi, Shivani Pandey
AGGRESSIVE FIBROMATOSIS OF MANDIBLE: 12
A CASE REPORT AND LITERATURE REVIEW
Nimisha Singh, Vibha Singh, Satish Dhasmana, Ridhi Jaiswal, Gagan Mehta
POLYALTHIA LONGIFOLIA AND ITS PHARMACOLOGICAL ACTIVITIES : REVIEW 17
Prateek Dixit, Tripti Mishra, Mahesh Pal, T. S. Rana and D. K. Upreti
USE OF GENE THERAPY TO CURE AIDS 26
Sudhir Mehrotra, Khushwant Singh, Pushkar Singh Rawat
A REVIEW ON SYNTHESIS, FABRICATION AND PROPERTIES OF 41
NANOSTRUCTURED PURE AND DOPED TIN OXIDE FILMS
B.C. Yadav, Raksha Dixit and Satyendra Singh
MINIMIZATION OF CONTACT TIME FOR TWO-STAGE BATCH 58
ADSORBER DESIGN USING SECOND-ORDER KINETIC MODEL
FOR ADSORPTION OF METHYLENE BLUE (MB) ON USED TEA LEAVES
S.P. Shukla, A. Singh, Lalji Dwivedi, K J. Sharma, D.S. Bhargava, R. Shukla,
N.B. Singh, V.P. Yadav, Markandeya
PROBLEM ANALYSIS DIAGRAM DECLARATIONS OF COMPILER TECHNIQUE 67
FOR APPLICATIONS OF C/C++ PROGRAMMING
Rohit Saxena, Deepak Singh, Amod Tiwari
A HIGH FIDELITY VERSION OF A THREE PHASE INDUCTION MOTOR 71
MODEL USING MATLAB/SIMULINKS
Harish Kumar Mishra, Anurag Tripathi
GREEN WALL: A METHODOLOGY FOR SUSTAINABLE 78
DEVELOPMENT USING GREEN COMPUTING
Ankit Kumar Srivastava, Neeraj Kumar Tiwari and Bineet Kumar Gupta
BIOCONTROL : AN OVERVIEW 83
Kalpana Singh
ECO-DEVELOPED SOCIETIES: A HOPE FOR THE FUTURE GENERATION 90
Monika Raghuvanshi
GREEN MARKETING AS A SOCIETAL CONCEPT 97
Monika Raghuvanshi
FORENSIC INSECTS FACILITATE ECOLOGICAL RECYCLING 105
Sunita Rawat, Reema Sonker and Kalpana Singh
DESIGN AND DEVELOPMENT OF AN ALGORITHM FOR ASSESSMENT OF 107
THE LEARNING STYLE OF SOFTWARE ENGINEERING STUDENTS
Ankita, K P Yadav
A STUDY OF VARIOUS WORMS AND THEIR DETECTION SCHEMES 115
Sucheta, K P Yadav
SURVEY AND ANALYSIS OF CURRENT WEB USAGE MINING SYSTEM AND TECHNOLOGIES 123
Vignesh V., K. Krishnamoorthy
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STUDY OF DATA MINING ALGORITHM IN CLOUD COMPUTING 129
USING MAP REDUCE FRAMEWORK
E. Gajendran, K P Yadav
A DHT ORIENTED PEER TO PEER NETWORK WITH NEW HASH FUNCTION 136
Vivek Saini, K P Yadav
PERFORMANCE ANALYSIS OF RELIABILITY GROWTH 142
MODELS USING SUPERVISED LEARNING TECHNIQUES
G Sarvanan, K Krishnamoorthy
STUDY AND ANALYSIS OF SINGLE POINT CUTTING TOOL UNDER VARIABLE RAKE ANGLE 150
Deepak Bhardwaj, B. Kumar
QUALITY FUNCTION DEPLOYMENT (QFD): A CASE STUDY 158
Satish Chander Garg, B. Kumar
MANUFACTURING QUALITY 169
Rohitash Kumar Kaushik, B Kumar
A COMPARATIVE STUDY ON EMISSIONS FROM TWO STROKE COPPER COATED 173
SPARK IGNITION ENGINE WITH ALCOHOLS WITH CATALYTIC CONVERTER
N L Maharaja, B. Kumar
OPTIMAL POWER FLOW BY PARTICLE SWARM 179
OPTIMIZATION FOR REACTIVE LOSS MINIMIZATION
G. Sridhar, Radhe Shyam Jha ‘Rajesh’
INDUSTRIAL POLLUTION AND RELATED LEGISLATIONS IN INDIA 186
M.I.Khan, Niaz Ahmed Siddiqui
CARBON TRADING : SUSTAINABLE DEVELOPMENT WITH 196
POTENTIAL WEALTH
Imran Farooq, Kamlesh Kumar Shukla
SOCIAL MEDIA AND ITS ROLE IN BRAND BUILDING 206
Shalini Bariar
IMPORTANCE OF LIFE INSURANCE IN MEETING OUT FINANCIAL NEEDS AND 210
SECURITY IN CURRENT SCENARIO WITH CHALLENGES AND EMERGING TRENDS
Jyoti Agarwal, S.C. Pandey
FDI IN INDIAN RETAIL SECTOR: ANALYSIS OF COMPETITION IN 216
AGRIFOOD SECTOR
P Nixon Dhas, N P Sharma
SIX SIGMA – DMAIC FRAMEWORK FOR ENHANCING QUALITY IN 226
ENGINEERING EDUCATIONAL INSTITUTIONS
Vikas Singh, N P Sharma
BIO MEDICAL WASTE: A SERIOUS ENVIRONMENTAL CONCERN 232
Kushagra Sah, Swapnil Srivastava, Shubham Singh
A CRITICAL STUDY ON FINANCIAL PERFORMANCE OF SIDBI 241
Prakash Yadava
ROLE OF GEOGRAPHICAL ENVIRONMENT ON ENVIRONMENTAL 244
DEGRADATION COGNITION IN TRIBAL AND NON-TRIBAL ZONES
Mahendra Singh, Rohtash Malik
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ANALYSIS OF RESPONSIVENESS & ASSURANCE DIMENSIONS OF 248
SERVICE QUALITY & CUSTOMER SATISFACTION IN INDIAN AIRLINES
Renuka Singh,
A STUDY ON MORAL JUDGMENT ABILITY OF TEENAGERS (14-19 YEAR) 255
Sunil Kumar Singh, Manisha Singh
E –GOVERNANCE IN HIGHER EDUCATION 261
S.K. Singh, Manisha Singh, Priyanka Singh
WOMEN EDUCATION FOR NATIONAL DEVELOPMENT IN INDIA 267
B.C. Tripathi, M. Awasthi, R. Shukla
ROLE OF E-GOVERNANCE TO STRENGTHEN HIGHER EDUCATION SYSTEM IN INDIA 270
Charanjeet Kaur, Prem Mehta
GROWTH OF HIGHER EDUCATION IN INDIA DURING THE PERIOD 1950-2005 277
Prem Yadav, Prem Mehta
VALUE-BASED EDUCATION: PROFESSIONAL DEVELOPMENT VITAL 281
TOWARDS EFFECTIVE INTEGRATION
Vinay Kumar, Prem Mehta
AIM, SCOPE & EDITORIAL POLICY OF THE JOURNAL 286
INSTRUCTION TO AUTHORS 287
SUBSCRIPTION FORM 291
UNDERTAKING 292
COVER LETTER 293
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www.ijsir.co.in 1
SIGNIFICANCE OFASCORBATE IN TRANS-PLASMA
MEMBRANE ELECTRON TRANSPORT IN HEALTH AND
DISEASE OF HUMANS: REVIEW
VARSHA SHUKLA, BABITA SINGH, A.A.MAHDI, * SHIVANI PANDEY
Department of Biochemistry, King Gorge’s Medical University, Lucknow, Uttar Predesh, India
*Dr. Shivani Pandey, Assistant Professor, Department of Biochemistry, King Gorge’s Medical University,
Lucknow, Uttar Pradesh, India,
email : drshivani111263@gmail.com
INTRODUCTION
Transplasma membrane electron transfer
(tPMET) systems are responsible for reducing
extracellular electron acceptor utilizing cytosolic
electron doners. In humans, NAD(P)H and
NADH-dependent systems have been
distinguished. tPMET activities are related to the
regulation of vital cellular processes including the
bioenergetics, regulation of growth and
differentiation, apoptosis, pH control and
mitogenesis cell signal transduction,
antioxidation, and iron/copper metabolism. In
accordance, deregulation of tPMET is related to
various human conditions which includes aging
and neurodegeneration, macrophage-mediated
LDL oxidation in atherogenesis , diabetic
nephropathy and glycolytic cancer progression
[1]
. A distinction was made between NAD(P)H and
NADH-dependent system, the NAD(P)H-
dependent system includes the members of the
Nox and Duox families [2]
, where as the NADH-
dependent system often referred to as the plasma
membrane NADH: oxidoreductase system or
PMOR-this system include at least an NADH
oxidase and an NADH: ferricyanide reductase
activity[3]
. By this cells can respond to change in
the redox microenvironment which is responsible
for regulating several biological functions such
as cell metabolism, proton pumping, activity of
ion channels, growth and death. Ascorbate
promotes the availability of iron from numerous
food sources in vivo and in vitro. Ascorbet
supplementation stimulates extracellular
ferricyanide reduction by several cell types,
including K562 cells [4]
, HL-60 cells and human
erythrocytes.
ABSTRACT
Trans-Plasma membrane electron transport (t-PMET) has been established in the year
1960s.This system (t-PMET system) transfer electron across the plasma membrane, which
results in the net reduction of extracellular oxidants (e.g., ferricyanide) at the cost of intracellular
reductants such as NADH and ascorbate. Ascorbate (vitamin C), helps in the protection of
organism against a variety of oxidative agents. Oxidation of ascorbate takes place in two one-
electron steps, the first step results in the Ascorbate Free Radical (AFR) formation. AFR can be
oxidized further to produce dehydroascorbic acid (DHA) and also two molecules of AFR
disproportionate to form one DHA and one ascorbet molecule. In humans, NAD(P)H- and NADH
dependent system have been distinguished. Recent finding suggest that transplasma membrane
ascorbate/dehydroascorbate cycling enhance NTBI reduction and uptake by human
erythroleukemia (K562) cells. By this phenomenon cell can respond to change in the redox
microenvironment which is responsible for regulating several biological functions such as cell
metabolism, proton pumping, and activity of ion channels, growth and death. This review will
give an update on functional significance of ascorbate in t-PMET and emphasis on its correlation
to some harmful diseases, such as cancer, abnormal cell death, cardiovascular diseases, aging,
obesity, metabolic syndrome etc. and genetically linked pathologies.
Keywords: Dehydroascorbate, ascorbate free redical, K562 cells, vitamin.
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BIOCHEMISTRY OF ASCORBATE
L-ascorbic acid (C6
H8
O6
) is the trivial/
common name of Vitamin C. The chemical name
of ascorbate is 2-oxo-L-threo hexono-1,4-
lactone-2,3-enediol. L-ascorbic and
dehydroascorbic acid are the major dietary forms
of vitamin C. The monovalent ascorbate anion
undergoes sequential one-electron oxidations
under physical condition of pH, temperature and
oxygen tension [5]
. The ‘first oxidation product is
relatively long-lived and electrochemically stable
ascorbet free radical (AFR; also known as semi-
or mono-dehydroascorbate;E’0
= +330mV .The
first oxidation step of ascorbate requires relatively
low levels of circulating redox-active transition
metals, such as iron and copper [2]
. AFR is
unreactive with dioxygen dissimilar to other free
radicals and it tends to decay mainly by
disproportionation, the formation of AFR takes
place by reaction of ascorbate with reactive
radical species which tends to inhibit free radical-
induced oxidative chain reactions and it is
irreversible reaction ; and rapidly AFR reduced
back to ascorbate. Further monoelectronic
oxidation of AFR produced DHA (E’0
= -210mV)
in the presence of mild oxidant such as
ferricyanide and /or NTBI species [4]
. In the
absence of oxidants, two AFR molecules rapidly
oxidized to form one ascorbate and one DHA
molecule (fig.1). Though oxidation (or
disporportionation) of AFR to DHA requires two-
electron reducing capacity of ascorbate, DHA is
a structurally labile species which rapidly
undergoes an irreversible hydrolytic reaction also
known as ring-opening reaction to form 2,3-
diketogulonic acid in plasma with a half-life of
several minutes[ 4]
Fig.1. The oxidation products of vitamin C.
These reactions mainly require enzymes,
e.g. glutaredoxin, thioredoxin reductase, or AFR
reductases, also chemical reduction by
glutathione alone has been described. When
extracellular oxidation occurs, then DHA
reduction takes place into the cell. In case of
erythrocytes, AFR and DHA can be reduced
extracellular by redox enzymes present in the
plasma membrane, which require intracellular
NADH as a source of reducing equivalents [6]
.
These are evidence of alternative pathway for
the reduction of extracellular ascorbate free
radicals in the erythrocyte (fig.2). The intracellular
ascorbate provides the reducing equivalents for
the reaction but not NADH, which utilized a
transmembrane redox enzyme. This reaction is
similar to the redox process present in the
adrenal chromaffine granules. There is possibility
of another, similar, erytherocyte redox system
responsible for the reduction of AFR. On the other
hand, it is suggested that electrons can be
transported to the membrane by small lipid
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soluble molecules like á-tocopherol and
coenzyme Q [7]
. DHA degradation results in a
complete loss of the vitamin from human systems
–it is a point which is particularly pertinent in the
case of species which lacks gulono-ã-lactone
oxidase activity. In order to overcome the loss of
ascorbate, the vitamin must be retained
predominantly in the two-electron reduced form
(i.e. ascorbate) in both intracellular and
extracellular biological fluids. This observation
implies that, human cells possess several
conservative reduction mechanisms for
maintaining both intra-and extracellular
ascorbate . Even cultured cells, which are
supplemented with artificial standard culture
conditions, maintain an extraordinary ability for
ascorbate regeneration [6]
.
Fig.2. Model for the Ascorbate-dependent reduction of AFR.
ASCORBATE-STIMULATED PLASMA
MEMBRANE FERRICYANIDE REDUCTASE
tPMET activity is present in human
erythrocytes that utilizes intracellular ascorbate
which acts as major electron donor for reduction
of extracellular ferricyanide .After increasing
intracellular ascorbate by dehydroascorbate,
stimulation of the plasma membrane ferricyanide
reductase activity takes place [8]
.By the addition
of ascorbate oxidation the stimulation of
ferricynade reductase activity is not affected (all
extracellular ascorbate is oxidized to form DHA
and inhibits direct reduction of ferricyanide by
ascorbate),therefore intracellular ascorbate acts
as an electron donor for reduction of extracellular
ferricyanide (Lane et al., data not shown).Direct
addition of ascorbate could not reproduce the
stimulation of reductase activity; hence these
cells do not express significant levels of sodium-
ascorbate co-transporters (SVCTs) [9]
.
CELLULAR DHA UPTAKE
Maximum human cells are able to maintain
intracellular ascorbate concentration that is
remarkably higher e.g. up to 30-fold in some
cases in comparison to the extracellular fluid or
plasma. Although most of the cells maintain
outward-facing concentration gradient by SVCT-
mediated ascorbate import [4]
, low-affinity, high-
capacity GLUTs is also a significant contributor
to facilitate the diffusion of DHA. An inward-facing
DHA gradient is maintained with respect to DHA
through rapid reduction of imported DHA back to
ascorbate by the cells; ascorbate is poor
substrate for GLUT-mediated transport [5]
.
Elevated level of intracellular ascorbate is seen
after loading the K562 cells with DHA. This is
inhibited by cytochalasin B. GLUTs is responsible
for DHA uptake by K562 cells which is evidenced
by two pharmacological observations, the
accumulation of intracellular ascorbate is
response to extracellular DHA inhibited by: i) low
micro molar concentration of cytochalasin B, but
not the structural analog dihydrochalasin B, the
latter of which shares with cytochalasin B, its
inhibition of cellular motile processes but not that
of facilitated glucose transport [4]
; and ii) millimolar
concentrations of the transportable ( but not
metabolizable) D-glucose analog 3-O-methyl-D-
glucose, but not the non-transportable glucose
stereoisomer L-glucose. Again, primary
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astrocytes demonstrate similar behavior (Lane
et al., data not shown).
IRON UPTAKE AND ASCORBATE / DHA
SHUTTLE
Cellular uptake of NTBI is well evidence, but
less well understood in comparison to the
classical transferrine-dependent iron import
pathway [9]
.Cellular uptake of NTBI may be
particularly related to in iron overload diseases
such as hereditary hemochromatosis,
hypotransferrinemia, and thalassemia , in which
plasma iron presents in excess of transferrine-
binding capacity [5]
.By the analysis of ascorbate-
mediated stimulation of NTBI reduction and
uptake by human erytheroleukemia ( K562) cells
it is found that DHA loading of cells stimulated
both processes ( viz. 12-and 2-fold, respectively),
yet unlike the reduction of ferricyanide- remained
inhibitable by extracellular ascorbate oxidase [9]
.
Furthermore, as cells were able to import iron in
a manner inhibitable by cell-impermant ferrous
ion chelators, the ascorbate-stimulated iron
uptake is clearly dependent on the initial adoption
of the ferrous state [8]
.
This suggests that ascorbate released from
cells- following uptake and reduction of DHA-
mediates direct reduction of ferric to ferrous iron,
ferrous iron is then imported ( fig. 3). Subsequent
addition of DHA to control or loaded cells resulted
in a dose-dependent stimulation of both iron
reduction and uptake that can be inhibited by
cytochalasin B, suggesting response-
dependence on DHA uptake via GLUTs. Again,
these results are basically reproducible with
primary astrocyte cultures [9]
.Several possible
candidates for the cellular export of ascorbate
have been proposed, including exocytosis of
ascorbate-containing vesicles, ascorbate-
ascorbate homeoexchangers ,connexin
hemi-channels and volume-sensitive osmolyte
and anion channels (VSOACs) .VSOAC
permeability and ascorbate efflux from cells can
be inhibited by generic anion channel inhibitors,
such as 4,4’-diisothiocyanatostilbene-2,2’-
disulfonic acid (DIDS) and 4-acetamido-4’-
isothiocyanatostilbene-2,2’-disulfonic acid
(SITS), suggesting that a significant proportion
of ascorbate release occurs via this pathway. It
has been observed that DIDS inhibits ascorbate
release, ferrireduction and iron uptake to similar
degree in K562 cells [4]
.
COMPOSITION OF T-PMET
The reduction of extracellular molecules
takes place by outward flow of electrons coming
from cytosolic donors, due to the action of tPMET.
Enzyme-mediated and/or shuttle-based electron
transfer is involved in this trans-plasma
membrane flow. (Fig. 5) [10, 11,12]
.
Identification of several components has
been done in last two decades and
characterization at the molecular and
biochemical level of some of these components
has been done. Among them, some are
expressed ubiquitously, some are present in
certain cell types, some utilize only a subset of
electron donor and acceptor and some are less
specific [13]
.
(A) Electron Donor: From NADH and NADPH,
intercellular reducing equivalents may be
derived, catabolic reactions are responsible for
production of first co-enzyme Q, where as
synthesis of fatty acid and cholesterol takes place
by the presence of NADPH/NADP+
system, these
reducing equivalent systems are also required
for hydroxylation and detoxification reactions.
Fig.3. Ascorbate/DHA shuttling in human NTBI
uptake
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Numerous biological functions are affected by the
ratios of NAD+
/NADPH [14, 15]
.To determine the
changes in these ratio, several biological
techniques such as bio-luminescence,
chromatography and cycling assays have been
developed. These techniques can determine the
change in ratio under both physiological and
pathological conditions. As living cells contain
enzymes, which are able to hydrolyze pyridine
nucleotides, technical problems may arise during
their extraction and these techniques also have
some limitations, such as concerning sensitivity,
reproducibility and interference with other
reducing compounds present in assay buffer[16]
.
Intercellular substance like flavonoids and
ascorbate (Asc) have been seen to protect cells
from extracellular oxidant stressors, in fact they
are crucial substrates for tPMET activity in red
blood cells, erythrocytes may encounter a verity
of oxidants that exert detrimental effects.
Abundantly present flavonoids in fruits and
vegetables are quercetin and myricetin, which
are utilized by erythrocytes and actively promote
tPMET activity. Their structure is responsible for
their ability to act as electron donor, the B ring
structure of catechol is necessary for the reducing
activity of these molecules [17]
. Red Blood Cells
are dependent on the intercellular Asc level, as
is evident from the observation that the treatment
of erythrocytes with nitroxide free radical Tempol
(2, 2, 6, 6,-tetramethyl-4-hydroxypiperidine-N-
oxyl) (fig.4) which is responsible for the
endogenous Asc depletion (without affecting
glutathione or á-tocopherol content) [18],
where as
inhibition of 80% basal rate of ferricyanide
reduction were seen in untreated cells [19,20]
.
Astrocytes show similar situation, in these cells
Asc-dependent tPMET is more important than the
NADH-dependent tPMET [21]
. There are two
important mechanisms, in which Asc contributes
to tPMET, are (i) enzyme-mediated electron
transport, in which electron donor is Asc for
transmembrane oxidoreductases and (ii) non
enzymatic electron transfer, where cells directly
release Asc which act as reducing agent thus
oxidized to dehydroascorbate (DHA) via
intermediate ascorbyl free radical (AFR) [22,23,24]
.
DHA further reduced back to Asc by the reducting
equivalents coming from cellular metabolite
shuttling/cycling mechanism involving other
redox couple including superoxidedioxygen [25,26],
dihydrolipoic acid/ á-lipoic acid [27,28]
and reduced
glutathione/cysteine [29].
(B) Electron Acceptor: Oxygen is most
important extracellular acceptor which fully
reduced to water with the generation of reactive
oxygen species (ROS) including superoxide (O2
-
) and hydrogen peroxide (H2
O2
) which help in the
modulation of specific cellular function and signal
transduction pathway [30]
. AFR is another
physiological substrate which reduced to Asc [24]
and ferric ion which again reduced to ferrous ion
[31]
, ferrous ion is important for the proximal small
intestinal epithelium, where enterocytes utilize
iron, but before its transportation across the
membrane occures it should be reduced.
( C ) Intermediate Electron Carriers:
Intermediate electron acceptors are mainly b
cytochromes, flavin and vitamin E, but most
widely used electron shuttle is ubiquinone (or
coenzyme Q [CoQ] ) (Fig.5). It is able to move
between membrane bi layer and links the cell
from inside to outside. [32]
FIG. 5. Key components of t-PMET
(D) Enzymes
1. NADPH oxidases
Superoxide families generating NADPH
oxidases also named as Nox or Phox i.e.
Fig.4.Structure of 2, 2, 6, 6,-tetramethyl-4-
hydroxypiperidine-N-oxyl
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phagocytic oxidases. It includes seven proteins
(Nox1 to Nox5 and Duox1 and Doux2) and is
best characterized class of enzymes present in
tPMET. Nox 2 is the first recognized and most
extensively studied member, expressed in
human phagocytes and responsible for
production of superoxide during engulfment of
invading microbes [33,34].
Members of Nox family
are involved in many biological functions such
as signal transduction, host defense,
development, angiogenesis, blood pressure
regulation and biosynthetic processes[35,36]
.
NADPH acts as electron donor for catalyzing the
reduction of oxygen to produce superoxide ,
hydrogen per oxide and oxygen with the help of
enzyme superoxide dismutase [SOD]. Hydrogen
peroxide so formed acts as second messenger
molecule. On the basis of structure, the Nox
enzymes are classified into three functional
groups. They are as follows.
1) Nox 1-4: Nox 2 is the first identified prototype
of this family. Cytochrome b558
, is the catalytic
part of Nox 2, it is heterodimer composed of
two sub nits, namely, p22phox
(light chain) and
gp91phox
(heavy chain) (37)
. Nox2 is usually
inactive in resting cells. Nox 1 is expressed in
color epithelial cells primarily and also found
in vascular smooth muscle cells, uterus and
prostate [38].
p22phox
is associated with Nox 1
like Nox 2, Nox 1 requires NoxO1 protein an
organizer and NoxA1 protein an activator. Nox
3 mRNAis found in foetal tissues, kidney, liver,
lung and spleen [39,40]
but mainly present in
inner ear like Nox 2 and Nox 1, it also requires
p22phox
but it does not require organizer and
activator protein for its enzyme activity. Finally,
the expression of Nox 4 is higher in kidney
and vascular endothelial cells [11,32].
Nox is able
to produce a functional diamer with p22phox
, it
can produce superoxide anions without
intervention of organism and activator protein
same like Nox 3.
2).Nox 5: It is found in testis and also expressed
itself in T- and B lymphocytes [41].
Nox 5 is also
related to the other members of the family. Its
activity does not require organizer and
activator protein, in this way it differs from
other Nox isoforms but it requires intercellular
calcium concentration and is totally depend
on it. In Nox 5 calcium sensitization is archived
by two main mechanisms.
a). The first mechanism involves protein
kinase C –dependent phosphorylation of
Thr494 and Ser 498 present in the FAD
binding domain.[42]
b). The second mechanism involves
calmodulin binding site present in the NADPH
binding domain. [43]
3) Duox 1and Duox 2: Expression of these
oxidases is mainly found in the membrane of
thyroid glands [43].
They usually produce H2
O2
rather than O2
.They have the basic structure
of gp91phox
enzymes [44].
Therefore superoxide
anions are mainly produced which rapidly
converted to H2
O2
by the help of enzyme
dismutase, this process is known as
dismutation.They have an additional N-
terminal peroxidase like domain present on
the outside membrane. These enzymes are
calcium responsive enzyme. [45]
Biological Function
· Nox 1 plays two important roles: immune
defense and cell proliferation.
· Nox 2 helps in signaling and also involves
in immune defense, it is present in endothelial
cells and responsible for endothelial growth
factor and thrombin and also implicate in new
blood vessel formation. They are also
responsible for tumor cell proliferation.
· Most important function of Nox 3 is
participation in normal vestibular functions as
it is present in the inner ear.
· In kidney Nox 4 helps in oxygen sensing and
regulation of erythropoietin synthesis. It also
acts as an antimicrobial system as it helps in
detoxification of urine wastes by releasing
ROS in glomerular filter.
· Main function of Nox 5 is in testis as it
promotes oxidative changes which are
usually associated with sperm capacitation
and acrosome reaction.
2. NAD(P)H: quinone oxidoreductase
It is also known as DT-diaphorase or QR1.It
is present in cytosole and is homodimeric flavor
protein. Its enzyme commission number is
1.6.99.2. Under oxidative condition it is over
expressed and trans located to plasma
membrane. [46, 47]
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Biological Function
• It is a key enzyme for cellular defense against
ROS.
• It shows scavenging activity due to the
presence of NAD(P)H-dependent
superoxidase.
• It is responsible for ubiquinone cycle and
facilitates in-out transfer of electron [48]
and it
also produces redox-labile hydroquinone.
Therefore it has a complex metabolic
pathway for its protective functions.
• It acts as chemo-protective enzyme, as it is
able to reduce quinine-imines, nitro- and azo-
compounds.
• It helps in detoxification of xenobiotics and
prevents cytotoxic and carcinogenic effects
[49]
.
• It is able to modulate oncoprotein stability.
3. Disulfide-thiol exchangers: They belong to
the family of cell surface proteins and exhibit
hydroquinone (NADH) oxidase activity and
protein disulfide-thiol interchange activity [50]
.
They are also known as ENOX proteins as they
are located outer side of plasma membrane [50]
.
Biological Function: It possesses two important
biological functions, first function is to participate
in enlargement of cell growth and the second
function is that it is the important component of
biological clock.
4. Voltage-dependent anion-selective
channels: It represents a family of 30-35 kDa
integral membrane protein. They are located in
outer mitochondrial membrane [51]
.
Biological Function:
· Its major function is to control metabolic
trafficking between cytosole and
mitochondria by forming pores which are
permeable to low molecular weight
molecules such as ATP, ADP, succinate and
citrate [52]
.
· They also help in the release of apoptogenic
proteins from mitochondria. [53]
5. Duodenal cytochrome b: Dcytb is also
known as Cybrd1, it is the member of cytochrome
b561 family Dcytb mRNA and protein both are
induced in response to hypoxia and iron
deficiency, they play an important role in iron
metabolism.[31]
Biological Function: It plays an important role
in uptake of dietary nonheme iron.
6. Cytochrome b5
reductase: Its enzyme
commission number is 1.6.2.2, also known as
diaphorase-1 or methemoglobin reductase.
Biological Function
· They are membrane associated enzymes
present in all human cells, it helps in fatty
acid chain elongation and desaturation [54, 55]
,
cholesterol synthesis [56]
and hydroxylation of
xenobiotics such as hydroxylamine and
amidoxime compounds [57].
In erythrocytes
they help in maintaining hemoglobin in its
reduced state. [58,59]
PATHOLOGICAL ROLES OF ASCORBATE IN
T-PMET
Various pathological conditions are
regulated by ascorbate in tPMET . These are
described below.
Apoptosis
This process is involved in body
homeostasis and tissue development. Defect in
the process of apoptosis leads to several
diseases: Hypotrophy can be caused by
excessive apoptosis; insufficient amount of
apoptosis can cause cancer due to uncontrolled
cell proliferation. [60, 61, 62]
.
ROS generates due to inhibition of
ascorbate in t-PMET which leads to pro-oxidant
at plasma membrane and promotes apoptosis.
Cancer
Through mitochondrial oxidative
phosphorylation, normal tissues derive their
energy by glucose metabolism and produce
carbon dioxide and water. Even in the presence
of oxygen cancer cells convert glucose into
lactose rather than pyruvate. This phenomenon
is known as Warburg effect [63].
Ascorbate plays
an important role in cancer biology .It may perturb
key redox couples which include NAD(P)H/
NAD(P)+
and CoQH2
/Co Q ratio, it neutralizes free
radicals before they can damage DNA and initiate
tumor growth and or may act as a pro-oxidant
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helping body’s own free radicals to destroy
tumors in their early stages [64,65].
The t-PMET is
useful for anticancer drug development due to
its targeting. Recently Prata et al. reported that
in human leukemic cells the primary site of action
of new anticancer compound is t-PMET such as
[ 3 - ( 2 - c h l o r o - 5 - m e t h o x y - 6 - m e t h y l - 3 -
indolylmethylene)5-hydroxy-1,3-dihydroindol-2-
one,3-[(2,6-dimethylimidazo[2,1-b]-thiazol-5-
yl)methylene]-5-methoxy-2-indolinone and
guanylhydrazone of 2-chloro-6-(2,5-dimethoxy-
4-nitrophenyl) imidazo [2, 1-b] thiazole-5-
carbaldehyde] having anti- proliferative activity,
therefore for the treatment of leukemia, specific
targeting of t-PMET may be utilized in
combination of ascorbate with standard
chemotherapeutic drugs. Treatment with ascorbyl
stearate resulted in concentration-dependent
inhibition of cell proliferation cancer cells [66, 67].
The anti-proliferative effect was found to be due
to the arrest of cells in S/G2-M phase of cell cycle,
with increased fraction of apoptotic cells.
Considerable biochemical and physiological
evidence suggests that ascorbic acid functions
as a free radical scavenger and inhibits the
formation of potentially carcinogenic N-nitroso
compounds from nitrates, nitritess in stomach
and thus offers protection against cancer [68–69].
Cardiovascular diseases
t-PMET regulates cardiovascular diseases
by controlling the redox state and so, the redox-
dependent signaling pathways in endothelial
cells. It has been proved that
Hyperhomocysteinemia stimulates ferricyanide
reductase activity and cytochrome b5 reductase
expression, thus forming a potential link between
t-PMET, oxidative stress, and endothelial
dysfunction [70]
; Jessup’s et.al. found that
enhanced t-PMET activity induces low-density
lipoprotein oxidation [71],
thus up regulation of t-
PMET may be numbered among atherogenic
factors. Nox1, Nox2 and Nox4 provide new
avenues for therapeutic interventions. Regular
physical exercise training has also improved
endothelium dependent vasodilatation, by down
regulating Nox subunits, especially gp91phox,
p22phox, and Nox4 [72]
. A potential protective role
of t-PMET has been reported by Lee at.el.
However, a recent meta analysis on the role of
ascorbic acid and antioxidant vitamins showed
no evidence of significant benefit in prevention
of CHD [73].
Thus, no conclusive evidence is
available on the possible protective effect of
ascorbic acid supplementation on cardiovascular
disease.
Aging
Ascorbate present in t-PMET plays a
protective role by maintaining the optimal levels
of plasma antioxidants. In line with this
hypothesis, caloric restriction, a common
intervention able to delay age related oxidative
damage [74]
, increases the amounts of CoQ10 and
á-tocopherol, as well as the activity of several
NAD(P)H oxidoreductases. Hence, up regulation
of t-PMET would be useful to decrease oxidative
stress and confers an anti-aging, stress resistant
phenotype, thus extending life span [75].
Obesity, metabolic syndrome and diabetes
Obesity represents a world wide nutritional
problem, as it dramatically increased during the
past 20 years. An unbalanced redox state has
been implicated as one of the key factors leading
to obesity-associated complications, such as the
metabolic syndrome and diabetes. Thus, obesity
may be viewed as a state of chronic oxidative
stress, characterized by enhanced levels of ROS
and impaired antioxidant defenses. t-PMET is
likely to participate in the chronic oxidant/
antioxidant unbalance due to presence of vitamin
C. Indeed, Nox1, Nox2, and/or Nox4 have been
shown to be implicated in pathways leading to
steatosis and insulin resistance in the liver, as
well as to pancreatic B-cell dysfunction, thereby
allowing progression from the metabolic
syndrome to type 2 diabetes [76].
CONCLUSIONS
Cell plasma membranes have complex
signaling systems for regulating cellular
metabolism. Several research studies basically
concentrate on enzymatic tPMET systems;
however several examples of ‘shuttle- based’
tPMET systems have been documented as well,
including ascorbate/DHA , dihy- drolipoic acid/a-
lipoic acid , reduced glutathione/cysteine and
superoxide dioxygen shuttles. t-PMET
unregulated optimal NAD+
level which is required
for the production of ATP in glycolysis under low
mitochondrial activity whereas increased activity
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is responsible for superoxide anion and hydrogen
per oxide production which enhance cell growth
by regulating signaling molecule[1].
As with
classical enzyme-mediated tPMET systems,
these ‘shuttle-based’ systems result in the net
transfer of metabolically derived reducing
equivalents from the cytoplasmic compartment
to the extracellular space. In the extracellular
space, the fate of these reducing equivalents
depends on the particular redox couple involved.
Many enzymes present in t-PMET have inducible
systems, which are activated by variety of
extracellular effectors such as growth factors,
cytokines and hormones, so that oscillation of
ROS production serves the need of different
tissues. The example of shuttle-based tPMET is
transplasma membrane ascorbate/DHA cycling,
which leads to redox change linked to cell
metabolism. Transplasma membrane ascorbate
DHA cycling may contribute significantly to NTBI
ferric reduction prior to ferrous uptake. As an
example, superoxide production at cell surface
may not be derived from any of NOX isoform
action, non -mitochondrial oxygen consumption
was inhibited by extracellular NADH in several
glycolytic cancer cell lines [77],
whereas the oxygen
burst observed in activated platelets and
leukocytes was demonstrated to be stimulated
by the presence of exogenous NADH [78].
From
the involvement of ascorbic acid present in t-
PMET in several pathological conditions, it is
mandatory to understand, in the future, the
relative contribution of each oxidase system to
ROS generation and shuttle-based t-PMET
systems; this will help us to design novel
therapeutic approaches. Thus, though ascorbic
acid was discovered in 17th century and Trans-
Plasma membrane electron transport (t-PMET)
has been established in the year 1960s, their role
is important in human health and disease, still
remains a mystery [79].
REFERENCES
1. Lane DJ., and Lawen A. Transplasma membrane
electron transport comes in two flavors. Biofactors 2009;
34: 191–200.
2. De Pinto, V., Messina, A., Lane, D.J.R.., and Lawen, A:
Voltage-dependent anion-selective channel (VDAC) in
the plasma membrane. FEBS Lett. 2010; 584, 1793-
1799,
3. Lane, D.J.R. and Lawen, A: A highly sensitive
colorimetric microplate ferrocyanide assay applied to
ascorbate-stimulated transplasma membrane
ferricyanide reduction and mitochondrial succinate
oxidation. Anal. Biochem. 2008; 373, 287-295.
4. Lane, D.J.R. and Lawen, A: Non-transferrin iron
reduction and uptake are regulated by transmembrane
ascorbate cycling in K562 cells. J.Biol. Chem. 2008;
283, 12701-12708.
5. Lane, D.J.R., Robinson, S.R,, Czerwinska. H,
and Lawen, A: A role for Na+/H+ exchangers and
intracellular pH in regulating vitamin C-driven electron
transport across the plasma membrane. Biochem.
J. 2010; 428, 191-200 ,
6. De Pinto, V., Messina, A., Accardi, R., Aiello, R., Guarino,
F., Tommasello, M., Tommasino, M., Tasca, G., Casadio,
R., Benz, R., De Giorgi, F., Ichas, F., Baker, M.
and Lawen, A: New functions of an old protein: the
eukaryotic porin or voltage dependent anion selective
channel (VDAC). Ital. J. Biochem. 2003; 52, 17-24.
7. Baker, M. A. and Lawen, A: The function of the plasma
membrane NADH-oxidoreductase system. A critical
review of the structural and functional data. Antioxidants
and Redox Signaling, Antioxid. Redox Signal. 2000;
2, 197-212.
8. Baker, M. A., Lane, D.J.R., Ly, J. D., De Pinto, V.
and Lawen, A: Voltage dependent anion channel 1 is
an NADH:ferricyanide reductase. J. Biol. Chem. 2004;
279, 4811-4819.
9. Vaillant, F., Larm, J. A., McMullen, G.L., Wolvetang, E.J.
and Lawen, A: Effectors of the mammalian plasma
membrane NADH-oxidoreductase system. Ubiquinone
analogues as potent stimulators. J. Bioenerg.
Biomembr. 1996; 28, 531-540.
10. Ly JD and Lawen A. Transplasma membrane electron
transport: enzymes involved and biological function.
Redox Rep. 2003; 8: 3–21.
11. Fischer H. Mechanisms and function of DUOX in
epithelia of the lung. Antioxid Redox Signal. 2009; 11:
2453–2465.
12. Lane DJ and Lawen A. Ascorbate and plasma
membrane electron transport—enzymes vs efflux. Free
Radic Biol Med 2009; 47: 485–495.
13. Lane DJ and Lawen A. Transplasma membrane electron
transport comes in two flavors. Biofactors. 2009; 34:
191–200.
14. Houtkooper RH, Canto´ C, Wanders RJ, and Auwerx J.
The secret life of NADþ: an old metabolite controlling
new metabolic signaling pathways. Endocr Rev. 2010;
31: 194–223.
15. Ying W. NADþ=NADH and NADPþ=NADPH in cellular
functions and cell death: regulation and biological
consequences. Antioxid Redox Signal. 2008; 10: 179–
206.
16. Zhang Z, Yu J, and Stanton RC. A method for
determination of pyridine nucleotides using a single
extract. Anal Biochem. 2000; 285: 163–167.
17. Fiorani M and Accorsi A. Dietary flavonoids as
intracellular substrates for an erythrocyte trans-plasma
membrane oxidoreductase activity. Br J Nutr .2005; 94:
338–345.
18. May JM, Qu Z-C, and Mendiratta S. Protection and
recycling of a-tocopherol in human erythrocytes by
intracellular ascorbic acid. Arch Biochem Biophys 349:
20. 10 www.ijsir.co.in
International Journal of Scientific and Innovative Research 2014; 2(1): 1-11,
P-ISSN 2347-2189, E- ISSN 2347-4971
281–289, 1998.
19. May JM, Qu Z-C, and Whitesell RR. Ascorbic acid
recycling enhances the antioxidant reserve of human
erythrocytes. Biochemistry. 1995; 34: 12721–12728.
20. May JM. Is ascorbic acid an antioxidant for the plasma
membrane? FASEB J. 1999; 13: 995–1006.
21. Lane DJ, Robinson SR, Czerwinska H, and Lawen A. A
role for Naþ=Hþ exchangers and intracellular pH in
regulating vitamin C-driven electron transport across the
plasma membrane. Biochem J. 2010; 428: 191–200.
22. Lane DJ and Lawen A. Transplasma membrane electron
transport comes in two flavors. Biofactors .2009; 34:
191–200.
23. Lane DJR and Lawen A. Non-transferrin iron reduction
and uptake are regulated by transmembrane ascorbate
cycling in K562 cells. J Biol Chem .2008; 283: 12701–
12708.
24. VanDuijn MM, Van der Zee J, and Van den Broek PJ.
The ascorbate-driven reduction of extracellular
ascorbate free radical by the erythrocyte is an
electrogenic process. FEBS Lett . 2001; 491: 67–70.
25. Ghio AJ, Nozik-Grayck E, Turi J, Jaspers I, Mercatante
DR, Kole R, and Piantadosi CA. Superoxide-dependent
iron uptake: a new role for anion exchange protein 2.
Am J Respir Cell Mol Biol.2003; 29: 653–660.
26. Nozik-Grayck E, Piantadosi CA, van Adelsberg J, Alper
SL, and Huang YCT. Protection of perfused lung from
oxidant injury by inhibitors of anion exchange. Am J
Physiol Lung Cell Mol Physiol. 1997; 273: L296–L304.
27. Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, and
May JM. Uptake, recycling, and antioxidant actions of
a-lipoic acid in endothelial cells. Free Radic Biol Med
.2002;33: 83–93.
28. May JM, Qu ZC, and Nelson DJ. Uptake and reduction
of a-lipoic acid by human erythrocytes. ClinBiochem.
2007;40: 1135–1142.
29. Dringen R, Pfeiffer B, and Hamprecht, B. Synthesis of
the antioxidant glutathione in neurons: supply by
astrocytes of CysGly as precursor for neuronal
glutathione. J Neurosci.1999;19:562–569.
30. Fisher AB. Redox signaling across cell membranes.
Antioxid Redox Signal. 2009; 11: 1349–1356.
31. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager
G, Mudaly E, Mudaly M, Richardson C, Barlow D,
Bomford A, Peters TJ, Raja KB, Shirali S, Hediger MA,
Farzaneh F, and Simpson RJ. An iron-regulated ferric
reductase associated with the absorption of dietary iron.
Science .2001; 291:1755–1759.
32. Arroyo A, Kagan VE, Tyurin VA, Burgess JR, de Cabo
R, Navas P, and Villalba JM. NADH and NADPH-
dependent reduction of coenzyme Q at the plasma
membrane. Antioxid Redox Signal .2000; 2: 251–262.
33. Cheng G, Cao Z, Xu X, van Meir EG, and Lambeth JD.
Homologs of gp91phox: cloning and tissue expression
of Nox3, Nox4, and Nox5. Gene. 2001; 269: 131–140.
34. Sumimoto H. Structure, regulation and evolution of
Noxfamily NADPH oxidases that produce reactive
oxygen species. FEBS J .2008; 275: 3249–3277.
35. Geiszt M and Leto TL. The Nox family of NAD(P)H
oxidases: host defense and beyond. J Biol Chem. 2004;
279: 51715–51718.
36. Nauseef WM. Biological roles for the NOX family NADPH
oxidases. J Biol Chem. 2008; 283: 16961–16965.
37. Parkos CA, Allen RA, Cochrane CG, and Jesaitis AJ.
Purified cytochrome b from human granulocyte plasma
membrane is comprised of two polypeptides with relative
molecular weights of 91,000 and 22,000. J Clin
Invest.1987; 80: 732–742.
38. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu
D, Chung AB, Griendling KK, and Lambeth JD. Cell
transformation by the superoxide-generating oxidase
Mox1. Nature. 1999; 401: 79–82.
39. Kikuchi H, Hikage M, Miyashita H, and Fukumoto M.
NADPH oxidase subunit, gp91(phox) homologue,
preferentially expressed in human colon epithelial cells.
Gene. 2000; 254:237–243.
40. De Deken X, Wang D, Many MC, Costagliola S, Libert
F, Vassart G, Dumont JE, and Miot F. Cloning of two
human thyroid cDNAs encoding new members of the
NADPH oxidase family. J Biol Chem.2000; 275: 23227–
23233.
41. Banfi B, Molnar G, Maturana A, Steger K, Hegedus B,
Demaurex N, and Krause KH. A Ca(2þ)-activated
NADPH oxidase in testis, spleen, and lymph nodes. J
Biol Chem. 2001; 276:37594–37601.
42. Griendling KK, Sorescu D, and Ushio-Fukai M. NAD(P)H
oxidase: role in cardiovascular biology and disease. Circ
Res. 2000; 86: 494–501.
43. De Deken X, Wang D, Many MC, Costagliola S, Libert
F, Vassart G, Dumont JE, and Miot F. Cloning of two
human thyroid cDNAs encoding new members of the
NADPH oxidase family. J Biol Chem. 2000; 275: 23227–
23233.
44. Pachucki J, Wang D, Christophe D, and Miot F. Structural
and functional characterization of the two human
ThOX=Duox genes and their 5’-flanking regions. Mol
Cell Endocrinol. 2004; 214: 53–62.
45. Ameziane-El-Hassani R, Morand S, Boucher JL, Frapart
YM, Apostolou D, Agnandji D, Gnidehou S, Ohayon R,
Noe¨l-Hudson MS, Francon J, Lalaoui K, Virion A, and
Dupuy C. Dual oxidase-2 has an intrinsic Ca2þ-
dependent H2O2-generating activity. J Biol Chem. 2005;
280: 30046–30054.
46. Hyun DH, Emerson SS, Jo DG, Mattson MP, and de
Cabo R. Calorie restriction up-regulates the plasma
membrane redox system in brain cells and suppresses
oxidative stress during aging. Proc Natl Acad Sci U S A.
2006; 103: 19908–19912.
47. Navarro F, Navas P, Burgess JR, Bello RI, De Cabo R,
Arroyo A, and Villalba JM. Vitamin E and selenium
deficiency induces expression of the ubiquinone-
dependent antioxidant system at the plasma membrane.
FASEB J. 1998;12:1665–1673.
48. Villalba JM, Navarro F, Co´rdoba F, Serrano A, Arroyo
A, Crane FL, and Navas P. Coenzyme Q reductase from
liver plasma membrane: purification and role in trans
plasmamembrane electron transport. Proc Natl Acad Sci
U S A. 1995; 92:4887–4891.
49. Li R, Bianchet MA, Talalay P, and Amzel LM. The
threedimensional structure of NAD(P)H:quinone
21. International Journal of Scientific and Innovative Research 2014; 2(1): 1-11,
P-ISSN 2347-2189, E- ISSN 2347-4971
www.ijsir.co.in 11
reductase, a flavoprotein involved in cancer
chemoprotection and chemotherapy: mechanism of the
two-electron reduction. Proc Natl Acad Sci U S A. 1995;
92: 8846–8850.
50. Morre´ DJ, Chueh P-J, Lawler J, and Morre´ DM. The
sulfonylurea- inhibited NADH oxidase activity of HeLa
cell plasma membranes has properties of a protein
disulfide–thiol oxidoreductase with protein disulfide–thiol
interchange activity. J Bioenerg Biomembr. 1998; 30:
477–487.
51. Colombini M. Structure and mode of action of a voltage
dependent anion-selective channel (VDAC) located in
the outer mitochondrial membrane. Ann N Y Acad Sci.
1980; 341: 552–563.
52. Benz R. Permeation of hydrophilic solutes through
mitochondrial outer membranes: Review on
mitochondrial porins. Biochim Biophys Acta. 1994; 1197:
167–196.
53. Zaid H, Abu-Hamad S, Israelson A, Nathan I, and
Shoshan-Barmatz V. The voltage-dependent anion
channel-1 modulates apoptotic cell death. Cell Death
Differ. 2005;12: 751–760,
54. Keyes SR and Cinti DL. Biochemical properties of
cytochrome c-dependent microsomal fatty acid
elongation and identification of products. J Biol Chem.
1980; 255: 11357–11364.
55. Oshino N, Imai Y, and Sato R. A function of cytochrome
b5 in fatty acid desaturation by rat liver microsomes. J
Biochem (Tokyo). 1971;69: 155–167.
56. Reddy VV, Kupfer D, and Capsi E. Mechanism of C-5
double bond introduction in the biosynthesis of
cholesterol by rat liver microsomes. J Biol Chem. 1977;
252: 2797–2801.
57. Kurian JR, Bajad SU, Miller JL, Chin NA, and Trepanier
LA. NADH cytochrome b5 reductase and cytochrome
b5 catalyze the microsomal reduction of xenobiotic
hydroxylamines and amidoximes in humans. J
Pharmacol Exp Ther. 2004; 311: 1171–1178.
58. Hultquist DE and Passon PG. Catalysis of
methaemoglobin reduction by erythrocyte cytochrome
B5 and cytochrome B5 reductase. Nat New Biol. 1971;
229: 252–254.
59. Passon PG and Hultquist DE. Soluble cytochrome b 5
reductase from human erythrocytes. Biochim Biophys
Acta. 1972; 275: 62–73.
60. Hotchkiss RS, Strasser A, McDunn JE, and Swanson
PE. Cell death. N Engl J Med. 2009; 361: 1570–1583.
61. Kurokawa M and Kornbluth S. Caspases and kinases
in a death grip. Cell. 2009; 138: 838–854.
62. Wang C and Youle RJ. The role of mitochondria in
apoptosis. Annu Rev Genet. 2009; 43: 95–118.
63. Warburg O. (Eds). The Metabolism of Tumors. London:
Constable & Co, 1930.
64. Cameron E and Pauling L: Supplemental ascorbate in
the supportive treatment of cancer: Prolongation of
survival times in terminal human cancer. Proc Natl Acad
Sci USA 1976; 73:3685-3689.
65. Murata A, Morsige F and Yamaguchi H: Prolongation of
survival times of terminal cancer patients by
administration of large doses of ascorbate. Int J Vit Nutr
Res Suppl 1982; 23:103-113.
66. Naidu AK, Karl RC, Naidu KA and Coppola D: The
antiproliferative and pro-apoptotic effect of Ascorbyl
Stearate in Human pancreatic cancer cells : Association
with decreased expression of insulin-like growth factor
receptor-1. Digest Dis Sci. 2003;48:230-237.
67. Naidu AK, Naidu KA, Sun M, Dan HC, Nicosia SV, Cheng
JQ and Coppola D: Ascorbyl stearate inhibits
proliferation and induces apoptosis of human ovarian
carcinoma cells by targeting PI3k/akt pathway.
Communicated to J Biol Chem 2003.
68. Schorah CJ, Sobala M, Collis N and Primrose JN: Gastric
juice ascorbic acid: effects of disease and implications
for gastric carcinogenesis. Am J Clin Nutr 1991,
53:287S-293S
69. Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah
CJ, White KL, Chamers DM and Axon AT: Ascorbic acid
may protect against human gastric cancer by
scavenging mucosal oxygen radicals. Carcinogenesis.
1996; 17:559-562.
70. Rodrý´guez-Alonso J, Montan˜ ez R, Rodrý´guez-Caso
L, and Medina MA. Homocysteine is a potent modulator
of plasma membrane electron transport systems. J
Bioenerg Biomembr. 2008; 40: 45–51.
71. Baoutina A, Dean RT, and Jessup W. Trans-plasma
membranenelectron transport induces macrophage-
mediated low density lipoprotein oxidation. FASEB J.
2001; 15: 1580–1582.
72. Adams V, Linke A, Krankel N, Erbs S, Gielen S, Mobius-
Winkler S, Gummert JF, Mohr FW, Schuler G, and
Hambrecht R. Impact of regular physical activity on the
NAD(P)H oxidase and angiotensin receptor system in
patients with coronary artery disease. Circulation. 2005;
111: 555–562.
73. Ness A, Egger M and Davey-Smith G: Role of antioxidant
vitamins in prevention of cardiovascular disease. Br Med
J. 1999;319:577-579.
74. Zainal TA, Oberley TD, Allison DB, Szweda LI,
andWeindruch R. Caloric restriction of rhesus monkeys
lowers oxidative damage in skeletal muscle. FASEB J.
2000; 14: 1825–1836.
75. Hyun DH, Hernandez JO, Mattson MP, and de Cabo R.
The plasma membrane redox system in aging. Ageing
Res Rev. 2006; 5:209–220.
76. Guichard C, Moreau R, Pessayre D, Epperson TK, and
Krause KH. NOX family NADPH oxidases in liver and in
pancreatic islets: a role in the metabolic syndrome and
diabetes? Biochem Soc Trans. 2008; 36: 920–929.
77. Herst PM and Berridge MV. Cell surface oxygen
consumption: a major contributor to cellular oxygen
consumption in glycolytic cancer cell lines. Biochim
Biophys Acta. 2007; 1767: 170–177.
78. Del Principe D, Mancuso G, Menichelli A, Gabriotti M,
Cosmi EV, and Gherardi G. Production of hydrogen
peroxide in phagocyting human platelets: an electron
microscopic cytochemical demonstration. Biol Cell.
1980; 38: 135–140.
79. Herst PM and Berridge MV. Plasma membrane electron
transport: a new target for cancer drug development.
Curr Mol Med. 2006; 6: 895–904.
22. 12 www.ijsir.co.in
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AGGRESSIVE FIBROMATOSIS OF MANDIBLE:
A CASE REPORT AND LITERATURE REVIEW
NIMISHA SINGH1
,* VIBHA SINGH1
, SATISH DHASMANA2
, RIDHI JAISWAL3
, GAGAN MEHTA1
1
Department of Oral and Maxillofacial Surgery, K.G. Medical University, Lucknow, Uttar Pradesh, India, 2
Department of
Anaesthesia, R.M.L.Institute of Medical Sciences, Lucknow , Uttar Pradesh, India, 3
Department of Pathology and
Microbiology, K.G. Medical University, Lucknow, Uttar Pradesh, India
*Address for Correspondence: Dr. Vibha Singh, Professor, Dept.s of Oral and Maxillofacial Surgery
,K.G.Medical University, Lucknow, Uttar Pradesh, India,
email: vibhasinghraghuvanshi@gmail.com
ABSTRACT
Aggressive fibromatosis or desmoid tumor is a benign but locally-aggressive tumor, which most
often affects the muscles of the shoulder, the pelvic girdle, and the thigh. This tumor has high
potential for loco regional extension. It is very rarely located in the mandible. The differential
diagnosis with malignant tumors is difficult. Surgery is the first-line treatment. However, alternative
therapies should be considered, especially in children, to avoid mutilating operations. This article
reports a case of aggressive fibromatosis involving mandible in a 13 year old female and literature
review.
Keywords: Desmoid, Fibromatosis, Mandible.
INTRODUCTION
Desmoid tumors (DT), also called
aggressive fibromatosis (AF), are rare
neoplasms, occurring both sporadically and in
the context of familial adenomatous polyposis,
also recognized as Gardner’s syndrome.
Fibromatoses are a group of fibrous connective
tissue lesions that are morphologically classified
as benign neoplasms. They do not usually
develop distant metastasis, however, locally they
show an aggressive and infiltrative behavior. The
low incidence of this rare tumor presents
problems in both diagnosis and management.
Juvenile aggressive fibromatosis affects infants
and children and requires radical surgery.
Stout[1]
first described ‘juvenile fibromatosis’
as a non-congenital disease affecting children
younger than 16 years. There are two types of
juvenile aggressive fibromatosis, superficial and
deep. The superficial variant is not aggressive,
does not grow faster, and does not invade deep
tissues. By contrast, deep fibromatosis is more
aggressive and invades other tissues. Some
authors tend to classify it as a fibroblastic
proliferative disorder different from neoplasia [2]
.
This variant affects young children, especially
those from 18 months to 3 years old, and females
in a 3:1 ratio over males[3]
. It affects different
regions of the body but especially the neck and
face, specifically the tongue and lower jaw [2,3,4,5]
.
This disease is characterized by a massive
infiltration of muscle, fat tissue, and bone.
The etiology is unknown. Multiple factors are
thought to influence pathogenesis including
genetic, trauma and endocrine factors.
Membrane-specific estrogen and progesterone
receptors have been implicated in desmoids in
pregnancy and steroid hormones play a vital role
in the dysregulation of fibroblast activity. Loss of
the Y chromosome and deletion of 5q
chromosome may occur [6]
.
Fibromatosis occurs mostly in the lower
abdominal wall of females during or after
pregnancy [7]
. Extra abdominal fibromatosis often
affects the muscles of the shoulder and pelvic
girdles. Between 7% and 15% of AFs occur in
the head and neck region, 26% of which arise
from the soft tissues (including the periosteum)
around the mandible [8,9]
. Fibromatoses are more
common in females than males at a ratio of 3:2
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or even higher for the abdominal desmoids [9]
.
Although fibromatosis can affect any age
group from neonatal to elderly, it is predominantly
a disease of children and young adults. Twenty
five percent of all AFs occur in children under 15
years of age[1]
. Surgical ablation in this kind of
tumor should be radical, as there is a high rate
of recurrences after more conservative treatment
[5,10,11]
.
CASE REPORT
A 13 year old female
presented to Outpatient
Department of Oral &
Maxillofacial Surgery,
K.G.Medical University,
Lucknow with a firm swelling
Fig 1: Frontal view showing
large swelling of right lateral
mandible.
in the right lateral mandible measuring 11x6 cm,
without involvement of skin or gingiva. (Fig. 1)
There was no history of trauma to the face
or neck and no complaints of pain, voice change,
or dysphagia. No relevant diseases were
reported in the family. A general physical
examination was normal. Oral and maxillofacial
examination revealed a large swelling of the right
lateral mandible. It extended from the right ramus
of the mandible to the left parasymphyseal
region, crossing the mid line. The mass was firm,
hard, non-pulsating, and measured 11x6 cm. The
swelling obliterated the right buccal sulcus and
was palpable in the floor of the mouth. The
overlying skin and mucosa were normal. No
cervical lymphadenopathy was present.
The orthopantomograph revealed a radio-
lucent lesion with ill-defined borders extending
from the right mandibular ramus to the left
parasymphysis (Fig. 2). A CT scan showed a
tumour arising from the right mandibular ramus,
extending to the anterior mandibular body,
crossing midline with erosion of the lingual and
buccal cortical plates at some places, and
extending towards the floor of the mouth and
submandibular area (Fig. 3).
Fig 2: OPG showing radio-lucent lesion from the right
mandibular ramus to left parasymphysis.
Fig 3: CT scan showing radiolucent tumor.
The patient underwent an intraoral incisional
biopsy. Sections show a benign mesenchymal
tumor disposed in bundles or fascicles or an
interlacing pattern. The fascicles comprise of oval
to elongated cells having uniform spindle nuclei
(Fig. 4a). Collagen formation is seen. At the
periphery several bone trabeculae rimmed by
osteoblasts and covered by squamous
epithelium are seen (Fig. 4b). The histological
examination revealed aggressive fibromatosis.
Fig 4a: Microscopic picture showing mesenchymal tumor
disposed in intersecting fascicles.
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Fig 4b: Microscopic picture showing osteoid rimming the
tumor tissue.
The patient was planned for surgery under
general anaesthesia for radical excision. A right
mandibulectomy was performed via a
submandibular incision (Fig 5, 6). Immediate
reconstruction was performed by using
reconstruction plate (Fig. 7).
Fig 5: Exposure of tumor via submandibular approach
Fig 6: Resected tumor mass
Fig 7: Immediate reconstruction of mandible with
reconstruction plate
Postoperative healing was uneventful (Fig.
8). Naso-enteral feeding was continued for 6
days, after which the patient was kept on a liquid
oral diet.
Fig 8: Post-operative view
of patient
DISCUSSION
Fibromatosis encompasses a group of soft
tissue lesions which are characterized
histologically by fibroblastic proliferation and
clinically by the potential to infiltrate locally and
to recur after surgical excision, but not
metastasize.
Seper et al.[11]
presented a complete
literature of aggressive fibromatosis of the
mandible reported between 1960 and 2003. Out
of 37 published cases, most (89%) underwent
surgical resection with 22% of recurrences
reported after an average follow up of 3.8 years.
The tumor is very rare in the maxilla. We know
only 15 cases that have been reported from1980
to now12, 13
.
The incidence of these lesions in the head
and neck is mentioned as from 9.5% to 50% of
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all desmoids tumors.[14] Within this area, 40%
to 80% of the tumors are located in the neck[15]
.
The face is mentioned as the second most
frequent site for desmoids lesions, with
preponderance in the region of the cheek [15]
.
Clinically, AF manifests as a painless, firm,
rapidly enlarging mass, fixed to underlying bone
or soft tissue. Histologically, AFs are tumors with
proliferation of mature fibroblasts with long ovoid
nuclei without polymorphism. Abundant collagen
is present with the neoplastic cells.
Radiographic findings are variable ranging
from periosteal thickening with ill-defined
radiolucency to frank bony destruction. CT and
MRI show infiltration of soft and hard tissue
boundaries [4]
.
The osteolysis of the mandible with a large
extra oral swelling but without involvement of the
mucosal or skin surface could indicate the
presence of a primary osseous lesion. Therefore,
AF could be misdiagnosed as desmoplastic
fibroma, in particular because it has a similar
histopathol[ogical appearance [16]
.
Estrogen, progesterone receptors and anti-
estrogen binding site studies may be of clinical
importance, as a therapy with hormonal agents
might be effective in AF [17]
.
According to the literature, surgery is the
most common treatment of AF in head and neck
with local invasion into the mandible [18,19]
.
Extensive and mutilating resection of a benign
neoplasm is a difficult decision. However, the
disease can result in a lethal outcome. Therefore,
complete excision of AF with a generous border
of histologically tumor-free tissue is generally
recommended [3 ,5 ,20]
. When bone is involved, the
treatment has to include the affected part of the
mandible.
Owing to the locally aggressive progression
of AF and patient’s uncompleted growth, the
treatment of head and neck lesions in young
children needs multidisciplinary approach. The
therapy alternatives in AF include Chemotherapy
[21]
hormonal therapy (antiestrogen), NSAID
therapy[22]
. Radiotherapy is reserved for
inoperable disease and chemotherapy may be
useful as an adjunct.
CONCLUSION
Aggressive fibromatosis presents a
diagnostic dilemma and may mimic malignancy.
The differential diagnosis with malignant tumors
is difficult. Fibromatosis in the maxillofacial
region is a very rare among diverse pathologic
conditions, and because of the rarity of this tumor,
definite treatment regimen is not established,
which may be responsible for a high recurrence
rate of these tumors. Surgery is the first-line of
treatment, however, alternative therapies should
be considered, especially in children, to avoid
mutilating operations.
REFERENCES
1. Stout AP: Juvenile fibromatoses. Cancer 7: 953–978,
1954
2. Zachariades N, Papanicolaou S: Juvenile fibromatosis.
J Craniomaxillofac Surg 16: 130–135, 1988
3. Hoffman CD, Levant BA, Hall RK: Aggressive infantile
fibromatosis: report of a case undergoing spontaneous
regression. J Oral Maxillofac Surgery 51: 2043–2047,
1993
4. Tullio A, Sesenna E, Raffaini M: Aggressive juvenile
fibromatosis. Minerva Stomatol 39: 77–81, 1990
5. De Santis D: Fibromatosis of the mandible : case report
and review of previous publications. Br JOral Maxillofac
Surgery 36: 384–388, 1998
6. Meera Satish Ruparelia 1, Daljit K. Dhariwal : Infantile
fibromatosis: a case report and review of the literature.
Br JOral Maxillofac Surgery 2011
7. Pack GT, Ehrlich HE. Neoplasms of the anterior
abdominal wall with special consideration of desmoid
tumours: experience with 391 cases and collective
review of the literature. Int Abstr Surg 1944;79: 177
8. Reitamo JJ, Scheinin TM, Havry P. The desmoid
syndrome. New aspects in the cause, pathogenesis and
treatment of the desmoids tumor. Am J Surg
1986;151:230-7
9. Carr RJ, Zaki GA, Leader MB, Langdon JD. Infantile
fibromatosis with involvement of the mandible. Br J Oral
Maxillofac Surg 1992;30:257-62.
10. Zlotecki RA, Scarborough MT, Morris CG, Berrey BH,
Lind DS, Ennekind WF, Markus Jr RB: External beam
radiotheraphy for primary and adjuvant management
of aggressive fibromatosis. Int J Radiat Oncol Biol Phys
54: 177–181, 2002
11. Seper L, Burger H, Vormoor J, Joos U, Kleinheinz J:
Aggressive fibromatosis involving the mandible—case
report and review of the literature. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 99: 30–38, 2005
12. Donohue WB, Malexos D, Pham H. Aggressive
fibromatosis of the maxilla. Report of a case and review
of the literature. Oral Surg Oral Med Oral Pathol
1990;69:420–6.
26. 16 www.ijsir.co.in
International Journal of Scientific and Innovative Research 2014; 2(1): 12-16,
P-ISSN 2347-2189, E- ISSN 2347-4971
13. Tenglong Hua,, Guangping Jing, Kewen Lv : Aggressive
fibromatosis in the maxilla. Br JOral Maxillofac Surgery
2009
14. Das Gupta TIC, Brasfield RD, O’Hara J. Extra-
abdominal desmoids: a clinicopathological study. Ann
Surg 1969; 170:109-21.
15. Conley T, Healey WV, Stout AD. Fibromatosis of the
head and neck. Am J Surg 1966;112:609-14.
16. Addante RR, Laskin JL. Large right mandibular mass.
J Oral Maxillofac Surg 1985;43:531-6.
17. Wilcken N, Tattersall MHN. Endocrine therapy for
desmoids tumors. Cancer 1991;68:1384-8.
18. Melrose RJ, Abrams AM. Juvenile fibromatosis affecting
the jaws. Report of 3 cases. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1980;49:317-24
19. Akama MK, Chindia ML, Guthua SW, Nyong’o A.
Extraabdominal fibromatosis invading the mandible:
case report. East Afr Med J 2002;79:49-51
20. Spear MA, Jennings LC, Mankin HJ, Spiro IJ,
Springfield DS, Gebhardt MC, et al. Individualizing
management of aggressive fibromatoses. Int J Radiat
Oncol Biol Phys 1998;40:637-45.
21. Azzarelli A, Gronchi A, Bertulli R, Tesoro JD, Baratti D,
Pennacchioli E, et al. Low-dose chemotherapy with
methotrexate and vinblastine for patients with advanced
aggressive fibromatosis. Cancer 2001;92:1259-64.
22. Lackner H, Urban C, Kerbl R, Schwinger W, Beham A.
Noncytotoxic drug therapy in children with unresectable
desmoids tumors. Cancer 1997;80:334-40.
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P-ISSN 2347-2189, E- ISSN 2347-4971
www.ijsir.co.in 17
POLYALTHIA LONGIFOLIAAND ITS PHARMACOLOGICAL
ACTIVITIES : REVIEW
PRATEEK DIXITa
, TRIPTI MISHRAa
, MAHESH PALa*
, T. S. RANAb
AND D. K. UPRETIb
*a
Phytochemistry Division, CSIR-National Botanical Research Institute, Lucknow 226 001, India, b
Plant Diversity,
Systematics and Herbarium Division, CSIR-National Botanical Research Institute, Lucknow 226001, India
*Address for Correspondence : Dr. Mahesh Pal, Principal Scientist, Phytochemistry Division CSIR-National
Botanical Research Institute, Lucknow 226 001, India
E.mail: drmpal.nbri@rediffmail.com
ABSTRACT
Polyalthia longifolia var. angustifolia is a member of the Annonaceae family and is a small
medium-sized tree distributed in many tropical countries around the world, commonly used as
ornamental street tree due to its effectiveness in combating noise pollution. In traditional and
indigenous systems of medicine Polyalthia longifolia has been commonly used in the treatment
of fever, helminthiasis, diabetes and in cardiac problems. Various pharmacological investigations
have shown that Polyalthia longifolia posseses significant biological and pharmacological
activities such as antibacterial, antifungal, antitumor, anti-ulcer, antidiabetic and antioxidant
properties. In context of various medicinal importance of P. longifolia, this review is an attempt
to compile detailed exploration of all currently available botanical, phytochemical,
pharmacological and other ethnomedicinal properties of P. longifolia in an attempt to provide a
direction for further research work.
Keywords: Polyalthia longifolia, Phytochemistry, Pharmacological Actions.
INTRODUCTION
Herbs and the humans have a great
relationship with each other. Plants have been
known to be used for alleviation and
management of diseases since the very
beginning of human civilization. Even at present
day medicinal plants play important roles despite
the tremendous scientific development and hold
much more hidden treasure to be explored as
almost 80 percent of the human population in
developing countries is dependent on plant
resources for their primary healthcare [1].
Plant-
based therapy has been used as a vital
component in traditional medicine systems and
also serves as the main source of inspiration for
several major pharmaceutical drugs used in the
defence against various diseases. One such
plant Polyalthia longifolia (Order: Magnoliales ;
Family : Annonaceae) is an evergreen plant
commonly used as an ornamental street tree due
to its effectiveness in combating noise pollution.
Polyalthia longifolia is also known as false
Ashoka, Buddha Tree, Green champa, Indian
mast tree, and Indian Fire tree. It exhibits
symmetrical pyramidal growth with willowy
weeping pendulous branches and long narrow
lanceolate leaves with undulate margins. The
tree is known to grow over 30 ft in height. In
traditional medicines various herbal preparations
are being used for treating dueodenal ulcers. The
plant has been used in traditional system of
medicine for the treatment of fever, skin diseases,
diabetes, hypertension and helminthiasis. A
number of biologically active compounds have
been isolated from the plant [2].
The leaves of the
plant are aromatic and are generally used for
decoration, while the bark is used as a folk
medicine for the treatment of pyrexia and other
bleeding disorders in India [3].
Ethanomedically
Polyalthia longifolia is a versatile plant which is
used to treat rheumatism, menorrhagia, scorpion
sting, diabetes, skin disease, hypertension,
helminthiasis and also in treatment for the
digestive system [4].
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International Journal of Scientific and Innovative Research 2014; 2(1): 17-25,
P-ISSN 2347-2189, E- ISSN 2347-4971
DISTRIBUTION
The genus Polyalthia includes about 120
species occurring mainly in Africa, South and
South Eastern Asia, Australia, and New Zealand.
India has 14 species of Polyalthia [5].
The
distribution of major Polyalthia species in India
are Polyalthia cerasoides Bedd.; a shrub or small
tree, found throughout India, Polyalthia fragrans
Benth ; a large tree found in Western Ghats and
P. longifolia (Sonn.) Thw ; found under cultivation
in India. There are two distinct varieties of this
species, both found in Maharashtra and
elsewhere [6].
PHYTOCHEMISTRY OF POLYALTHIA
LONGIFOLIA
Polyalthia longifolia is very versatile plant
due to its chemical constituents which are
responsible for its various pharmacological
actions. Literature report of few phytochemical
screening tests on this plant shows the presence
of saponins, carbohydrates, alkaloids, tannins,
resins, steroids, glycosides and flavonoids as
major phytochemical constituents. Previous
studies on its leaves, bark, roots, root bark, and
seeds have revealed various types of
diterpenoids and alkaloids with numerous
biological activities such as anti-inflammatory,
antihypertensive, antimicrobial, and cytotoxic
effects.
A new halimane diterpene, 3â,5â,16á-
trihydroxyhalima- 13(14)-en-15,16-olide, and a
new oxoprotoberberine alkaloid, (-)-8-
oxopolyalthiaine, along with 20 known
compounds, were isolated from a methanolic
extract of Polyalthia longifolia var. pendula.
These compounds were evaluated for cytotoxicity
toward a small panel of human cell lines [7].
Ethanolic extract of the leaves of P. longifolia
var. pendula showed the presence 16a-
hydroxycleroda-3,13(14) Z-dien-15,16-olide as
the active principle, and its metabolite 16-
oxocleroda-3, 13(14) Z-dien-15-oic acid as a
novel antidyslipidemic agent [8].
H
OH
HO
O
O
OH
Fig 1. 3 ,5 ,16 -
trihydroxyhalima-
13(14)-en-15,16-olide
N
H3CO
OH
O
OH
OCH3
OH
H
(-)-8-oxopolyalthiaine
O
O
OH
Fig. 2: 16a-hydroxycleroda-3,13(14)Z-dien-15,16-
olide & its metabolite
Other clerodanes like compounds also
reported from stem of P.longifolia by other
researchers are 6á,16-dihydroxycleroda-3,13-
dien-15-oic acid, 6á,16-dihydroxycleroda-
4(18),13-dien-15-oic acid, and 4á,18â-epoxy-16-
hydroxyclerod-13-en-15-oic acid [9]
as well as 16-
hydroxycleroda-13-ene-15,16-olide-3-one from
bark [10].
Isolation of the methanol extract of leaves
and berries shows the presence of three new
clerodane diterpene from this plant i.e. methyl-
16-oxo-cleroda-3,13(14)E-dien-15-oate, 3â,16á-
dihydroxy-cleroda-4(18), 13(14)Z-dien-15,16-
olide, and solidagonal acid [11].
Later, two other
clerodane diterpenes were obtained from leaves
and these were 3á,16 á-dihydroxycleroda-
4(18),13(14)Z-dien-15,16-olide and 3â,16 á-
dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide
[12].
The bark of Polyalthia longifolia has also
been reported to contain a new clerodane-type
HO
H
O
O
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P-ISSN 2347-2189, E- ISSN 2347-4971
www.ijsir.co.in 19
gamma hydroxylbutenolide diterpene i.e. (Z)-4-
hydroxy-3-(2"6"-hydroxy-5"-(hydroxymethyl)-
5",8"a-dimethyloctahydro-1H-spiro[naphthalene-
2",2"-oxiran]-1"-yl) ethylidene)dihydro-furan-
2(3H)-one [13].
Other than terpenoids the other major group
of chemical from this plant was alkaloid.
Azafluorene type of alkaloids are majorly found
in this plant which includes polylongine and
polyfothine [21]. Aporphine alkaloids were also
obtained which include methylnandigerine-â-N-
oxide as well as liriodenine, noroliveroline and
oliveroline-â-N-oxide [21, 22].
HO
O
OH
O
O OH
The dimeric clerodane diterpene has also
been isolated and two examples of this
bisclerodane compound are Longimide A and
Longimide B [14].
Fig. 3: Gamma hydroxy-
lbutenolide
COOH
N
O
O
Other than these compounds this plant has
also been reported to have 5-hydroxy-6-
methoxyonychine [15,16],
(-)-anonaine [17],
(-)-
norboldine [18],
(+)-norboldine, (-)-norpallidine [19],
(-)-asimilobine, p-hydroxybenzoic acid [20],
beta-
sitosterol and stigmasterol.
Fig. 4: Longimide B
Fig [5] 5-hydroxy-6-
methoxyonychine,
N
H3CO
OH
O
NH
O
O
(-)-anonaine
NH
H
OH
O
O
H
N
O
H3CO
H3CO
CH3
The protoberberine compounds obtained
has also been identified as (-)-8-oxo-polyalthiaine
[23], pendulamine A and pendulamine B [24].
Fig [6] polyfothine
noroliveroline
N
HO
O
OCH3
OH
OCH3
PHARMACOLOGICAL ACTIVITIES OF
POLYALTHIA LONGIFOLIA
(A) Antibacterial activity
Silver nanoparticles of Polyalthia longifolia
leaves extract were synthesized along with D-
sorbitol. These silver nanoparticles exhibited
excellent antibacterial activity against the
bacterial pathogens Staphylococcus aureus
(Gram positive), Escherichia coli, and
Pseudomonas aeruginosa (Gram negative) [25]
and indicated that the synthesized silver
nanoparticles have good antibacterial action
against Gram-positive organism than Gram-
Fig [7] Pendulamine A
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negative organisms. Results showed that the
effect of antibacterial activity against test
organisms (Escherichia coli, Pseudomonas
aeruginosa and Staphylococcus aureus) is
higher in the case of silver nanoparticles
synthesized at 60° C (8mm-16.4 mm) compared
to 25° C (7.3-14 mm) because of being smaller
in size [26].
Leaf extracts of Polyalthia longiflia (Debdaru)
treated with different solvents like hexane,
methanol and chloroform were subjected to in
vitro determination of antibacterial activity against
six tested pathogenic bacteria viz. Bacillus
subtilis, Sarcina lutea, Xanthomonas compestris,
Escherichia coli, Klebsiella pneumonia and
Pseudomonas sp. using agar disc diffusion
method and MIC determination test. The zone of
inhibition against the tested bacteria was found
ranging from 21.00 to 44.20mm. The highest
zone of inhibition produced by the hexane,
methanol and chloroform extracts of Polyalthia
longiflia at a concentration of 500ìg/10ìl against
pathogenic bacteria i.e. Sarcina lutea were found
41.80mm, 44.20mm and 43.50mm respectively.
The MIC values of all extracts against six tested
bacteria were almost 15.625 ìg/ 10ìl [27].
Polyalthia longifolia var. angustifolia stem
bark extracts were evaluated against six
important pathogenic bacteria viz. Escherichia
coli, Bacillus subtilis, Salmonella typhi, Proteus
mirabilis, Pseudomonas aeruginosa, Klebsiella
sp.and Staphylococcus aureus. The powdered
stem bark extracts were successively extracted
with petroleum ether, chloroform, methanol and
water using Soxhlet apparatus. The antibacterial
activity study was performed by both agar well
diffusion and serial dilution methods. The
petroleum ether extract was found to exhibit
highest activity against all tested bacteria [28]
(B) Antioxidant activity:
The antioxidant activities of the ethanolic
extract of Polyalthia longifolia seeds were
assayed using rat liver homogenate. Nitric oxide,
ferrous sulphate and carbon tetrachloride-
induced lipid scavenging activities were carried
out and showed significant free radical
scavenging activity. The percentage inhibition of
peroxide formation increased in a dose-
dependent manner [29].
Methanolic leaf extracts from Polyalthia
longifolia were evaluated for in vitro antioxidant
activity for free radical scavenging capacity, using
established in vitro models such as ferric-
reducing antioxidant power (FRAP), 2,2-
diphenyl-1-picryl-hydrazyl (DPPH), hydroxyl
radical (OH), nitric oxide radical (NO) scavenging,
metal chelating, and antilipidperoxidation
activities. The methanolic extracts of P. longifolia
exhibited concentration dependent antiradical
activity by inhibiting DPPH radical with inhibitory
concentration 50% (IC50) values of 2.721 ± 0.116
mg/mL [30].
The active constituents like quercetin,
quecetin-3-O-ß-glucopyranoside and rutin were
isolated from the ethanolic extract of the leaves
of the P. Longifolia and shows the antioxidant
capacity determined by their ability to scavenge
ABTS+
radical cation which was expressed using
Trolox Equivalent Antioxidant Capacity (TEAC)
assays [31].
(C) Anti-inflammatory activity
A clerodane diterpenoid 16-hydroxycleroda-
3,13(14)E-dien- 15-oic acid from P. longifolia
significantly inhibited the generation of
superoxide anion and the release of elastase in
formyl L-methionyl-L-leucyl-L-phenylalanine
(FMLP) activated human neutrophils in a
concentration-dependent fashion with IC50
values of 3.06±0.20 and 3.30±0.48 ìM,
respectively [32].
HOOC
H
CH2OH
Fig. 8: 16-hydroxycleroda-
3,13(14)E-dien-15-oic acid.
The anti-inflammatory potential of ethanolic
and aqueous extracts of P. longifolia leaf in albino
wister rats was evaluated using Cotton pellet
granuloma which is a sub-acute anti-
inflammatory model. All the extracts were found
to produce significant decrease in the granuloma
tissue as evident by the decrease in the weight
of cotton pellet when compared to the disease