| dc.contributor.advisor | Yalçın, Funda N | |
| dc.contributor.author | BAYAZEID, Omer | |
| dc.date.accessioned | 2017-08-18T10:08:46Z | |
| dc.date.available | 2017-08-18T10:08:46Z | |
| dc.date.issued | 2017-08-14 | |
| dc.date.submitted | 2017-07-14 | |
| dc.identifier.uri | http://hdl.handle.net/11655/3934 | |
| dc.description.abstract | Papaver species have been used for treating varieties of diseases including depression for centuries in Anatolia. We screened five Papaver species plant extracts for their antidepressant-like activity in
vivo and their influence on BDNF expression in SH-SY5Y cells in vitro. According to
the biological activity tests, the most active species in vivo and in vitro P. lacerum was
chosen for the phytochemical analysis. One new 5-O-(6-O-α-rhamnopyranosyl-β-
glucopyranosyl mevalonic acid (RGM) and one known Tyrosol-1-O-β-xylopyranosyl-
(1→6)-O-β-glucopyranoside (TXG) glycosides were isolated from the active extract,
which exhibited moderate effects on BDNF. To determine the metabolites related to
BDNF expression, commercially available main alkaloids in P. lacerum, (roemerine and
(+)-pronuciferine) were purchased and tested. Both roemerine, (+)-pronuciferine (20 and
10 µM) were significantly (p< 0.0001 - 0.001) active. LC-MS/MS analysis confirmed
that roemerine and (+)-pronuciferine exist in the active P. lacerum extract. To identify
possible effects of the isolated compounds TXG and RGM, in silico methods were used.
In silico results showed that both compounds might exhibit anticancer activity. To
confirm the in silico result, both compounds have been tested in vitro against HeLa cell
line to evaluate their cytotoxicity activities using MTT assay. As a result both TXG and
RGM were cytotoxic to HeLa cells with IC 50 from 54 – 66.4 µM. roemerine, (+)-
pronuciferine, TXG and RGM did not show any cytotoxicity to the normal cell line (L929
cells). | en |
| dc.description.sponsorship | TÜBİTAK Ph.D. fellowship (2215), Hacettepe University
Scientific Researches Coordination Unit (Project Number: 014 D11 301 003-734). | tr_TR |
| dc.description.tableofcontents | APPROVAL PAGE iii
YAYIMLAMA VE FİKRİ MÜLKİYET HAKLARI BEYANI iv
ETHICAL DECLARATION v
AKNOWLEDGMENTS vi
ABSTRACT vii
ÖZET viii
CONTENTS ix
ABBREVIATIONS xi
TABLES xiv
FIGURES xv
1. INTRODUCTION 1
2. GENERAL INFORMTION 4
2.1. Description of Plants 4
2.1.1. Family: Papaveraceae 4
2.1.2 Genus: Papaver L. 4
2.1.3. Papaver Species 5
2.1.4. Key to Papaver Species 9
2.2. Traditional Usage of Some Papaver Species 10
2.3. Biological Activity Studies on Papaver Species 11
2.4. Phytochemical Studies on Papaver Species 12
2.4.1. Alkaloids 12
2.4.2. Phenolics 30
2.5. Structures 31
2.6. Depression and BDNF 54
2.6.1. Neurotrophins and Depression 55
2.6.2. BDNF 55
2.6.3. BDNF Signaling 56
x
2.6.4. Antidepressants Mechanisms 59
2.6.5. Types of Antidepressants 60
3. MATERIALS AND METHODS 62
3.1. Plant Materials 62
3.2. Chemicals and Reagents 62
3.3. Animals 63
3.4. Devices and Machines 63
3.5. Extraction 64
3.6. Isolation 64
3.7. LC-MS/MS Studies 67
3.8. Biological Activities 68
3.8.1. In vivo Studies 68
3.8.2. In silico Study Design 69
3.8.3. In vitro Studies 72
4. RESULTS 76
4.1. Structure Elucidation 76
4.1.1. Compound I 76
4.1.2. Compound II 91
4.2. LC-MS/MS Results 105
4.3. Biological Activity Results 106
4.3.1. In vivo Results 106
4.3.2. In silico Results 109
4.3.3. In vitro Results 121
5. DISCUSSION 129
6. CONCLUSIONS AND FUTURE ASPECTS 134
7. REFERENCES 135
8. APPENDIX
App 1. ETHICAL COMMITTEE APPROVAL
9. CURRECULUM VITTAE | tr_TR |
| dc.language.iso | en | tr_TR |
| dc.publisher | Sağlık Bilimleri Enstitüsü | tr_TR |
| dc.rights | info:eu-repo/semantics/closedAccess | tr_TR |
| dc.subject | Depression | tr_TR |
| dc.subject | BDNF | |
| dc.subject | in silico | |
| dc.subject | cytotoxicity | |
| dc.title | Phytochemıcal and Pharmacologıcal Studıes on Some Papaver Specıes in Turkey | en |
| dc.title.alternative | Türkiye'deki Bazı Papaver Türleri Üzerinde Fitokimyasal ve Farmakolojik Çalışmalar | tr_TR |
| dc.type | info:eu-repo/semantics/doctoralThesis | en |
| dc.description.ozet | Papaver türleri Anadolu'da
yüzyıllar boyunca depresyon gibi bazı zihinsel hastalıkların tedavisinde kullanılmıştır.
Beş Papaver türünün ekstrelerini antidepresan benzeri aktiviteleri in vivo ve BDNF
ekspresyonu üzerindeki etkileri SH-SY5Y hücreleri üzerinde in vitro olarak
incelenmiştir. In vivo ve in vitro biyolojik aktivite testlerine göre P. lacerum, en aktif
bitki olarak bulunmuş ve fitokimyasal analizler için seçilmiştir. Aktif ekstreden bilinen
bir glikozit [Tyrosol-1-O-β-ksilopiranozil-(1→6)-O-β-glukopiranozit (TXG)] ile birlikte
yeni bir glikozit [5-O-(6-O-α-ramnopiranozil-β-glukopiranozil mevalonik asit (RGM)]
izole edilmiştir. Her iki bileşik de BDNF üzerinde orta etkili bulunduğundan ekstredeki
BDNF ekspresyonu ile ilişkili metabolitleri tespit etmek için P. lacerum’da bulunan ana
alkaloidler (roemerin, (+)–pronusiferin) denenmiştir. Hem roemerin hem de (+)-
pronusiferin (20 and 10 µM) SH-SY5Y hücrelerinde belirgin derecede (p< 0.0001 -
0.001) aktif bulunmuştur. LC-MS/MS analizleri, roemerin ve (+)-pronusiferinin P.
lacerum ekstresinde bulunduğunu doğrulamıştır. TXG ve RGM bileşiklerinin olası
biyolojik etkilerini tespit etmek için uygulanan in silico testler her iki bileşiğin de
antikanser etkili olabileceğini göstermiştir. Her iki bileşik de sitotoksik etkilerini
değerlendirmek için MTT yöntemiyle HeLa hücre dizisine karşı uygulanmıştır. TXG ve
RGM'nin her ikisi de HeLa hücrelerine karşı 54–66.4 µM IC50 ile sitotoksik etki
göstermiştir. TXG ve RGM, normal L929 hücre dizisine herhangi bir sitotoksisite
göstermemiştir. | tr_TR |
| dc.contributor.department | Farmakognozi | tr_TR |
