5%Phytochemical Investigation El Boukhary Thesis 2017.Pdf
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Phytochemical investigation of some plants grown in Lebanon and belonging to genera Salvia, Centaurea and Anthemis by Rima Mohammad Kheir El Boukhary Thesis Submitted in Partial Fullfillment of the Requirements for the Degree of PhD in Pharmacy Speciality: Pharmacognosy Department of Pharmaceutical Sciences Faculty of Pharmacy Supervised by Prof. Abdalla El Lakany Prof. Maha Aboul-Ela Professor of chem. of natural products Professor of Pharmacognosy Dean of the Faculty of Pharmacy Head of Department of Pharmaceutical sciences Beirut Arab University Faculty of Pharmacy Beirut Arab University 2017 Abstract Recently, modern science is beginning to research and verifying herbal remedies. Furthermore, Literature Survey indicated that, the Lebanese flora has not been yet extensively studied. For this reason, phytochemical investigation and pharmacological studies on well chosen plants used widely in Lebanese folk medicine were performed in order to prove their efficacy and safety. Accordingly, this work includes the study of three plants, namely: Salvia libanotica fruticosa (Lamiaceae), Centaurea horrida and Anthemis chia L. (Asteraceae), growing in Lebanon. Plants of genus Salvia are used in traditional folk medicine for their antidiabetic, antiinflammatory and anti-oxidant effects. From different extract of Salvia libanotica fruticosa, eight phenolic compounds were isolated. The chemical structures of the isolated compounds were determined by different spectroscopic methods. Among these compounds three Flavonoids named apigenin; luteolin and rutin were identified, in addition to three phenolic acids namely ferulic, gallic and rosemarinic. Moreover, carnosol and dehydro- abietic acid were isolated from the root extract. All the isolated compounds were obtained for the first time from this plant. On the other hand, plants of genus Centaurea are used in traditional medicine as antibacterial, choleretic, antipyretic and to cure various ailments as malaria and hypertension. Centaurea horrida has been used in folk medicine as diuretic, antiinflammatory, hypotensive, mild astringent, bitter tonic and emmenagogue. An infusion of this plant is used to treat diabetes and digestive problems. It is used as a wash for tired eyes and in conjunctivitis. C. horrida grown in Lebanon is widely used also in the treatment of diarrhea, as antihypertensive and as hypoglycemic. In this study, the phytochemical investigation of the species grown in Lebanon led to the isolation and identification of five phenolic compounds isolated from methylene chloride, ethyl acetate and acetone fractions of Centaurea extracts. Their structures were determined by different spectroscopic techniques. All the isolated compounds are obtained for the first time from Centaurea horrida growing in Lebanon and in the Mediterranean region. Moreover, plants of genus Anthemis are used in folk medicine for the treatment of gastrointestinal disorders, hemorrhoid and stomach ache. Anthemis chia L. grown in Lebanon is used in the treatment of cough, cold and as carminative in the form of an infusion. The three chosen plants showed significant antioxidant activity by determining DPPH scavenging activity and total Phenolic compounds. Salvia libanotica fruticosa extracts exerted powerful antiinflammatory activity in vivo. Both the aerial parts and the roots of the crude v extracts exhibited relevant protection at 4 h against carrageenan-induced mouse paw edema by 50% and 44% respectively. The anti-inflammatory activities of the aerial parts and the roots extracts relative to that of the standard drug diclofenac were 0.9 and 0.8 respectively in correlation with their phenolic constituents. Furthermore, the in vivo investigation of the hypoglycemic effect of Salvia libanotica fruticosa and C. horrida revealed marked antidiabetic effect in diabetic mouse model. Finally, Assessment of the antimicrobial activity of the three plants was carried out. All the biological studies were carried out for the first time on the three species growing in Lebanon. vi Table of Contents Title Page ……………………..………………………………...……………..…….. i Signature Page ……………..…………………………………..……………..……... ii Acknowledgments …………………………………………………………..…..…... iii Abstract ……………………………………………………….…..………..……….. v Table of Contents …………………………………………………………..………... vii List of Tables …………………………………………………………………….….. ix List of Figures ……………………………………..………………………………… xii List of Abbreviations …………………………………………..………..…………... xv General Introduction 1 PART 1 Chapter 1: Economical values of some species of genus Salvia ………………… 4 Genus Salvia in folk Medicine .............................................................. 5 Biological activities of genus Salvia …...……………………...……... 8 Previously isolated abietane diterpenoids from Genus 13 Salvia ……………………………………………………………….… Previously isolated flavonoids from genus Salvia …...….…………… 21 Previously isolated Phenolic acids ……………….…...…………….... 24 Chapter 2: Introduction ……….…………………………………………………. 27 Literature survey on Genus Centaurea ……………………..………… 28 Biological activities of Genus Centaurea …………………..………… 30 Previously isolated flavonoids from genus Centaurea …...…………... 37 Previously isolated phenolic acids from genus Centaurea …………… 40 Chapter 3: Literature survey of genus Anthemis ……………………...……..…... 42 Economical values of some species of genus Anthemis ……….…….. 43 Genus Anthemis in folk medicine ……………………………………. 43 vii Biological activities of genus Anthemis ……………………..………. 46 Previously isolated flavonoids from genus Anthemis ………..……… 51 Previously isolated phenolic acids from genus Anthemis …………… 52 Aim of study 53 Photographs of the Studied Plants 54 Material, Reagents and Apparatus 58 PART 2 Chapter 1: Extraction and isolation of eight materials from Salvia libanotica fruticosa Aerial parts and roots …………………………………… 62 Preliminary chemical examination of SLF …………….…………….. 64 Characterization of the isolated materials S1-S2 isolated from Salvia libanotica fruticosa …………………………………………………... 70 Discussions of materials S1, S2, S3, S4, S5 and S8 ……….…….…... 100 Chapter 2: Preliminary chemical examination of Centaurea horrida …………… 107 Extraction of Centaurea horrida ……………………………..……...... 107 Chapter 3: Characterization of the isolated materials C1-C5 ………….………… 111 Discussions of materials C1- C5 139 PART 3 Chapter 1: Anti-oxidant and anti-inflammatory activities of SLF…………..……. 146 Anti-oxidant and anti-inflammatory activities of Centaurea horrida 152 ………………………………………………………………………… Anti-oxidant and anti-inflammatory activities of Anthemis chia L …. 154 Chapter 2: Hypoglycemic activity of SLF and Centaurea horrida …………….... 157 Chapter 3: Assessment of the antimicrobial activity of SLF, Centaurea horrida and Anthemis chia L ……………………….…………………………. 163 References …………………………………………………………………………… 168 viii General Introduction: Modern science is beginning to research and verify herbal remedies that created “Herbal renaissance” in recent years. But; it should be admitted that, herbal medicine is not free from risks. Further investigation of their active chemical constituents, their therapeutic efficacy and safety must be the primary interest while developing them. Otherwise, Literature survey indicated that, the Lebanese flora has not been yet extensively studied. Genus Salvia, belonging to Family Lamiacea with about 900 species, is a rich source of terpenoids like citral, camphor and salvinorin A, polyphenols as well as essential oils. It is important to mention that salvinorin A was the first diterpene to be identified as hallucinogen in humans.The genus has been the subject of intensive study in the past decades for its antioxidative components (carnosic, rosmarinic acid and flavonoids) and antiviral activity against vesicular stomatitis virus. It is used as antitumor agents due to diterpenoid quinines (taxodiol and taxodene), as a treatment for hemorrhoids, as astringent, anti-diabetic and antispasmodic. Genus Centaurea is a large genus, belonging to Family Asteraceae, from the tribe Cynarea. Many Centaurea species have been used in folk medicine as diuretics, bitter tonics, and for their antibacterial, hypoglycemic and antitumor activities. Plants of the genus have been studied because of their chemical constituents such as sesquiterpene lactones, acetylenes and flavonoids. Many Centaurea plants have marked cytostatic and antineoplastic activities due to the sesquiterpene lactone cynaropicrin. Genus Anthemis, Family Asteracea, contains flavonoids and essential oils. The main constituents of the volatile oil are the monoterpenes α-pinene and terpinen-4-ol. Anthemis chia is used as antispasmodic, sedative, antiphlogistic and urinative. It helps to regenerate wounds and is used also in the treatment of inflamed air passages, bowel and cough remedy. 1 REFERENCES 1-Minhui, Li., Quianquan, Li., Na, Z., Chunhong, Z., Luqui, H., and Peigen, X. (2013). 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