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Study of Essential Oils and Phenolic Compounds; Their Changes and Anticancer Activity in Some Species Belonging to Asteraceae and Lamiaceae Families

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Study of Essential Oils and Phenolic Compounds; Their Changes and Anticancer Activity in Some Species Belonging to Asteraceae and Lamiaceae Families People’s Democratic Republic of Algeria Ministry of Higher Education and Scientific Research Larbi Ben M’hidi University - Oum El Bouaghi Faculty of Exact Sciences and Life Sciences and Nature Departement of Life Sciences and Nature Thesis Presented by: Maarfia Sara SUBMITTED FOR THE DEGREE OF: DOCTORAT OF SCIENCES In Biological Sciences Option: Applied Biochemistry Study of essential oils and phenolic compounds; their changes and anticancer activity in some species belonging to Asteraceae and Lamiaceae families. Discussed on: Members of jury: Chairman: Noureddine GHERRAF Prof. Larbi Ben M’hidi University Oum El Bouaghi Supervisor: Amar ZELLAGUI Prof. Larbi Ben M’hidi University Oum El Bouaghi Examiner: Lekhmissi ARRAR Prof. Ferhat Abbas University Setif Examiner: Noureddine CHAREF Prof. Ferhat Abbas University Setif Examiner: Youcef NECIB Prof. Mentouri Brothers University Constantine 1 2018/2019 I dedicate this research work To My Beloved Father and Loving Mother For Their Love And Support Most Precious For Me In This World, My Sisters My Family All My Teachers All My Friends And Colleagues i Acknowledgements In the name of ALLAH who gave me strength and courage to accomplish this task. I bow my head to Almighty ALLAH with the core of my heart who provided me the opportunity of exploring the texture of this natural beauty on the Applied Biochemistry level. At first, I would like to express my gratitude to my supervisor, Professor Amar Zellagui, for his constant support, patience and efficient supervision and for providing an amiable working environment. It was great to have the privilege to work with him and to learn from his expertise in the past years. I would like to thank the reviewers of my thesis, Professor Noureddine GHERRAF from University of Larbi Ben Mhidi, Oum El Bouaghi, Professor Lekhmissi Arrar from University of Ferhat Abbas, Setif, Professor Noureddine Charef from University of Ferhat Abbas, Setif, and Prof. youcef Necib from University of Constantine 1 for critical reading of the thesis, and for their valuable comments, discussions and suggestions. I am deeply indebted to Dr. Mohammed Najim Abed, Keele university, UK, for his assistance in the cytotoxicity and growth inhibitory studies, results interpretation and editing of the manuscript. I am very grateful for all his time, help and guidance and care during this work. I would like to extend my heartfelt gratitude Dr. Wen wu Li, Keele University, UK, for his warm hospitality, constructive criticism and encouragement during the part of my PhD at his lab, where I had the chance to develop my skills and find forward-looking friends. I extend my thanks to all other members of staff, technicians, and research students at the Guy Hilton Research Centre, the Institute for Science and Technology in Medicine (ISTM), and the royal stoke university hospital, Stoke on Trent, UK. I am so grateful to Pr. Sarker Satyajit, School Pharmacy, Liverpool John Moores University, Liverpool, UK, for giving me the opportunity to do experiments in his laboratory and for his help, advice and guidance during this period. ii Acknowledgements I am grateful to Dr. Afaf Al-Gorishi, Dr. Ismail Fyaz, Dr. Nicola Dempster, Dr. Lutfan Nahar and Dr. Andrew Evan, Liverpool John Moores University, Liverpool, UK, for their help, support and assistance during my internship in Liverpool. I would like to thank Professor Pr. Mehmet Hakki Alma, Kahramanmaraş Sütçü İmam University, Turkey; the opportunity gave to me to visit his laboratory and doing GCMS analysis. Many Thanks to Dr. Eyyüp Karaoğul for his help and continuous support during the GC-MS measurements. Special Thanks to Dr. Ali Göçeri for his assistance and support during and after my training. Many thanks to: Grira Abdeslem and Gaagae Karim for their help to collect the plants from different places. I am indebted to my friend and colleague, Dr. Bouhbila Azize for his cooperation, kind help throughout this study. I am very grateful for all of his time and attention during my work. Thanks to my colleagues with whom I shared these years of research in Biomolecules and Plant Breeding, laboratory, Oum El-bouaghi, algeria. I extend my warmest gratitude to my parents for unconditional support and encouragement. Life in a new place far from family is very difficult, thanks to all my friends in UK with whom the life has become easier and smoother, especially Dr. Abed Fadl Ali and his wife Dr. Eatelaf Muhammad Hassan. I will never forget your help and support. iii Contents Acknowledgements ii Abbreviationsx List of Schemes xiv Introduction Review of literature 1 Cancer disease 1.1 Introduction to cancer................................. 23 1.2 History of cancer ................................... 23 1.3 Cause of cancer.................................... 23 1.4 Old theories of cancer development ......................... 24 1.4.1 Humoral theory................................ 24 1.4.2 Lymph theory ................................ 24 1.4.3 Blastoma theory ............................... 25 1.4.3.1 The theory of chronic irritation.................. 25 1.4.4 Trauma theory ................................ 25 1.4.5 Parasite theory ................................ 25 1.5 The Role of oncogenes and tumor suppressor genes in cancer............ 25 1.5.1 Oncogenes .................................. 26 1.5.2 Tumor suppressor genes ........................... 26 1.6 Cancer screening and early detection......................... 26 1.7 Cancer therapeutics.................................. 27 1.8 Use of medicinal plants in cancer treatment ..................... 28 1.9 Plant derived anticancer agents............................ 29 Acknowledgements 1.10 Ovarian cancer .................................... 30 1.10.1 Introduction to ovarian cancer........................ 30 1.10.2 Epidemiology and incidence......................... 30 1.10.3 Aetiology of ovarian cancer ......................... 31 1.10.4 Types of ovarian cancer ........................... 32 1.10.5 Symptoms of ovarian cancer......................... 33 1.10.6 Staging and diagnosis ............................ 34 1.10.6.1 Staging of ovarian cancer..................... 34 1.10.6.2 Methods of ovarian cancer diagnosis............... 36 1.10.7 Therapy of ovarian cancer .......................... 37 1.10.7.1 Surgery............................... 37 1.10.7.2 Chemotherapy........................... 38 1.10.7.3 Platinum chemotherapy...................... 38 1.10.7.4 Taxanes .............................. 39 1.10.8 Resistance to chemotherapy ......................... 40 1.11 Natural products in cancer treatment......................... 41 1.11.1 Natural products in cancer treatment of ovarian cancer........... 41 1.11.1.1 Phytochemicals approved for the treatment of ovarian cancer . 41 1.11.1.2 Phytochemicals in clinical study for the treatment of ovarian cancer 41 1.11.1.3 Phytochemicals in preclinical study for the treatment of ovarian cancer ............................... 43 2 Species under investigation 2.1 Medicinal plants.................................... 45 2.2 Asteraceae family................................... 45 2.2.1 Classification of the studied Asteraceae species............... 46 2.2.2 The genus Centaurea L. (Centaurée)..................... 46 2.2.2.1 Morphological description and geographic distribution . 46 2.2.2.2 Ethnomedicinal uses of Centaurea L. species........... 47 2.2.2.3 Phytochemistry of Centaurea L. species ............. 47 2.2.2.4 Pharmacological properties of Centaurea L. species . 48 2.2.2.5 Centaurea sphaerocephala L.................... 48 v Acknowledgements 2.2.2.6 Phytochemistry of C. sphaerocephala L.............. 48 2.2.3 The genus Bellis L............................... 49 2.2.3.1 Morphological description and geographic distribution . 49 2.2.3.2 Phytochemistry and pharmacological properties of Bellis L. species 49 2.2.3.3 Pharmacological properties of Bellis L. species.......... 49 2.2.3.4 Bellis sylvestris L.......................... 50 2.2.3.4.1 Phytochemistry of Bellis sylvestris L........... 50 2.2.4 The genus Asteriscus Moench ........................ 50 2.2.4.1 Phytochemistry and pharmacological properties of Asteriscus Moench species .......................... 51 2.2.4.2 Asteriscus maritimus (L.) Less. (= Pallenis maritima (L.) Greuter) 52 2.2.4.2.1 Morphological description and geographic distribution of A. maritimus (L.) Less................. 52 2.2.4.2.2 Phytochemistry and pharmacological properties of As- teriscus maritimus (L.) Less............... 52 2.2.5 The genus Artemisia L. (Armoise)...................... 53 2.2.5.1 Ethnomedicinal uses of Artemisia L. species........... 53 2.2.5.2 Phytochemistry of Artemisia L. species.............. 53 2.2.5.3 Pharmacological properties of Artemisia L. species . 54 2.2.5.4 Artemisia campestris L....................... 54 2.2.5.4.1 Morphological description of Artemisia campestris L. 54 2.2.5.4.2 Geographic distribution of Artemisia campestris L. 54 2.2.5.4.3 Ethnomedicinal uses of Artemisia campestris L. 55 2.2.5.4.4 Phytochemistry of Artemisia campestris L. 56 2.2.5.4.5 Pharmacological properties of Artemisia campestris L. 56 2.3 Lamiaceae family................................... 56 2.3.1 Classification of the studied Lamiaceae species............... 57 2.3.2 The genus Lavandula L. (Lavender)..................... 57 2.3.2.1 Morphological description and geographic distribution of La- vandula L. species......................... 57 vi Acknowledgements 2.3.2.2 Phytochemistry and pharmacological properties of Lavandula L. species..............................
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