İran Astragaluslarından triterpen saponinlerin izolasyonu ve immün sistem üzerindeki etkilerinin araştırılması
Küçük Resim Yok
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Fabaceae (Leguminosae) familyasının üyesi olan Astragalus cinsi dünya üzerinde yaklaşık 2000 tür ile vasküler bitkiler arasında en büyük cinsi oluşturmaktadır. Bu cinsin Kuzey Amerika'da 372 ve Avrupa'da 133 türü tanımlanmıştır. Astragalus cinsi Türkiye'de 224 tanesi endemik olmak üzere 450 tür ile temsil edilmektedir (Çeçen vd, 2016; Davis, 1970). İran'daki bitki örtüsünde ise yaklaşık 900 türü bulunmaktadır (Osaloo vd., 2003). Bazı Astragalus türlerinin kurutulmuş köklerinden elde edilen Radix Astragali (RA), geleneksel tıpta hayvan ısırmaları ve zehirlenmelerinde, yaralanmalarda ve yanıklarda, lösemi ve rahim kanseri tedavilerinde iyileştirici etkisinden dolayı kullanılmaktadır (Çakilcioğlu ve Turkoğlu, 2010; Graf, 1992). Bugüne kadar yapılan çalışmalarda Astragalus türlerinden izole edilen oleanan ve sikloartan iskeletine sahip saponinlerin, antiviral (Gariboldi, 1995), immünostimülan (Çalış vd., 1997; Bedir vd., 2000c; Yeşilada vd., 2005; Nalbantsoy vd., 2011), kardiyotonik (Khushbaktova vd., 1994), sitotoksik (Radwan vd., 2004), anti-protozoal (Özipek vd., 2005), yara iyileştirici (Sevimli-Gür vd., 2011) gibi biyolojik aktiviteleri rapor edilmiştir. Grubumuz tarafından da Astragalus türlerinden birçok oleanan ve sikloartan tipi triterpen saponin izole edilmiş ve bu bileşiklerin immünostimülan, anti-protozoal, anti-kanser, sitotoksik aktivite ile birlikte hemoliz etkileri incelenmiştir (Bedir vd., 1998, 1999a,1999b; Çalış vd., 1997; Çalış vd., 2008; Polat vd., 2009, 2010; Horo vd., 2010, 2012; Savran vd., 2012; Gülcemal vd., 2011, 2012, 2013; Denizli vd., 2014). Astragalus türlerinden (AST) izole edilen saponinler üzerinde yapılan in vitro ve in vivo çalışmalar sonucunda bu grup bileşiklerin IL-2 seviyesini anlamlı şekilde indüklediği ortaya konmuştur (Yeşilada vd., 2005; Nalbantsoy vd., 2011, 2012). Astragalus türlerinin dünya üzerindeki yayılımı dikkate alındığında, bu bitkinin çeşitliliği yönünden en zengin ülke olan İran'da fitokimyasal ve/veya sekonder metabolitlerinin immünomodülatör etkileri üzerine kayda değer bir çalışma yapılmadığı görülmüştür. Sunulan doktora tezinde, İran/İran-Turan bölgelerine ait Astragalus türleri ve immünomodülatör aktiviteleri üzerine ileri çalışmaların yapılması hedeflenmiştir. Bu tez kapsamında, ince tabaka kromatografisi kullanılarak 22 İran-Turan Astragalus türü toplanmış ve bu türler içerisinden saponince zengin 3 Astragalus türü (Astragalus brachycalyx FISCHER, Astragalus karjaginii BORISS, Astragalus leiophyllus FREYN & BORNM) fitokimyasal olarak incelenmiş ve izole edilen bileşiklerin yapı tayinleri 1D- ve 2D-NMR, ESI-MS ve HR-MS kullanılarak yapılmıştır. Toplamda 3 farklı Astragalus bitkisinden 37 bileşik izole edilmiş ve bu bileşiklerden 4 tanesinin (3-O-?-D-ksilopiranozil-6-O-?-D-glukopiranozil-16-O-?-D-glukopiranozil-3?,6?,16?,24(S),25-pentahidroksisikloartan, 3-O-[?-L-arabinopiranozil-(1?2)-?-D-ksilopiranozil]-6-O-?-D-glukopiranozil-16-O-?-Dglukopiranozil-3?,6?,16?,24(S),25-pentahidroksisikloartan, 6?,16?,24(S),25-tetrahidroksi-sikloartan-3-on ve 6-O-?-D-ksilopiranozil-3?,6?,16?,24(S),25-pentahidroksisikloartan ) bilim dünyası için yeni olduğu saptanmıştır. Elde edilen ekstrelerin ve bazı bileşiklerin immün sistem üzerinde etkileri insan kanı kullanılarak immünomodülatör sitokinlerin salınımına etkisi ve insan eritrositlerine karşı hemolitik aktiviteleri yönünden incelenmiştir. Test edilen ekstre ve bileşiklerin (3 µg ve 6 µg dozlarla) IL-2, IL-17A ve INF-? sitokin salınımını anlamlı şekilde yükseltmiştir ancak test edilen ekstre ve bileşiklerin (2,5, 12,5, 25, 50, 125, 250, 500, 5000 ?g/mL dozlarla) herhangi bir hemolize neden olmadığı belirlenmiştir
The genus Astragalus, a member of the Fabaceae (Leguminosae) family, comprises the largest genus among the vascular plants with approximately 2000 species in the world. A total of 372 species in North America and 133 species of Astragalus in Europe were identified. Astragalus species are represented by 450 species from which 224 of them have been reported as endemic species in Turkey (Çeçen vd, 2016; Davis, 1970). Apart from this, there are approximately 900 species in the vegetation cover of Iran (Osaloo vd., 2003). Radix Astragali (RA), obtained from the dried roots of some Astragalus species, has been used in traditional medicine due to having some healing effects in animal bites, intoxications, injuries, burns, leukemia and uterine cancer treatments (Çakilcioğlu ve Turkoğlu, 2010; Graf, 1992). Accumulating data suggested that saponins with oleanan and cycloartan skeleton isolated from Astragalus species showed a variety of biological activities such as antiviral (Gariboldi, 1995), immunostimulant (Bedir vd., 2000c; Çalış vd., 1997; Yeşilada vd., 2005; Nalbantsoy vd., 2011), immunostimulants cardiotonic (Khushbaktova vd., 1994), cytotoxic (Radwan vd., 2004), anti-protozoal (Özipek vd., 2005) and wound healing (Sevimli-Gür vd., 2011) effects. Many oleanan and cycloartan type triterpene saponins from Astragalus species were isolated and these compounds were investigated with their immunostimulant, anti-protozoal, anti-cancer, cytotoxic activity as well as their haemolysis effects by our group (Çalış vd., 1997; Bedir vd., 1998, 1999a,1999b; Çalış vd., 1997; Çalış vd., 2008; Denizli vd., 2014; Gülcemal vd., 2011, 2012, 2013; Horo vd., 2010, 2012; Polat vd., 2009, 2010; Savran vd., 2012; Denizli vd., 2014). In vitro and in vivo studies on Astragalus saponins showed that these groups of compounds were significantly able to induce the levels of IL-2 (Nalbantsoy et al., 2012, 2011; Yeşilada et al., 2005). It was also reported that Astragalus extracts were used as immune system-stimulating drugs (Graf, 1992). There are no studies regarding to phytochemical and/or immunomodulatory effects of Iranian Astragalusto date. Therefore, it was aimed to carry out further studies on Astragalus species from Iran / Iran-Turan regions and discover their immunomodulatory activities in the current thesis a few Astragalus species gathered from Iran. In total, 37 compounds were isolated from 3 different Astragalus plants and 4 of these compoundsThe effects of the extracts and some compounds on the immune system were investigated in terms of their effect on the release of immunomodulatory cytokines using human blood and their hemolytic activities against human erythrocytes. Tested extracts and compounds (at doses of 3 2,5g and 6 veg) significantly increased IL-2, IL-17A and INF-? cytokine release, In this study, 22 Iran-Turan Astragalus species were investigated phytochemically by using thin-layer chromatography and 3 Astragalus species (Astragalus brachycalyx FISCHER, Astragalus carjaginii BORISS, Astragalus leiophyllus FREYN & BORNM), which were rich in saponins, were chosen for the current study and NMR was performed using ESI-MS and HR-MS. In total, 37 molecules were isolated from 3 different Astragalus plants of which 4 mollecules were found to be newly identified (3-O-?-D-xylopyranosyl-6-O-?-D-glucopyranosyl-16-O-?-D-glucopyranosyl-3?, 6?, 16? , 24 (S), 25-pentahydroxycycloartane, 3-O- [?-L-arabinopyranosyl- (1 ? 2) -?-D-xylopyranosyl] -6-O-?-D-glucopyranosyl-16-O-?- Dglucopyranosyl-3?, 6?, 16?, 24 (S), 25-pentahydroxycycloartane, 6?, 16?, 24 (S), 25-tetrahydroxy-cycloartan-3-one and 6-O-?-D-xylopyranosyl-3?, 6?, 16?, 24 (S), 25-pentahydroxycycloartane). The effects of the extracts and some molecules on the immune system were investigated in terms of their effect on the release of immunomodulatory cytokines using human blood and their hemolytic activities against human erythrocytes. The tested extracts and molecules showed significantly positive effects on cytokine release (IL-2, IL-17A and INF-?) while tested extracts and compounds (2,5, 12,5, 25, 50, 125, At 250, 500, 5000 ?g / mL) did not cause any hemolysis.
The genus Astragalus, a member of the Fabaceae (Leguminosae) family, comprises the largest genus among the vascular plants with approximately 2000 species in the world. A total of 372 species in North America and 133 species of Astragalus in Europe were identified. Astragalus species are represented by 450 species from which 224 of them have been reported as endemic species in Turkey (Çeçen vd, 2016; Davis, 1970). Apart from this, there are approximately 900 species in the vegetation cover of Iran (Osaloo vd., 2003). Radix Astragali (RA), obtained from the dried roots of some Astragalus species, has been used in traditional medicine due to having some healing effects in animal bites, intoxications, injuries, burns, leukemia and uterine cancer treatments (Çakilcioğlu ve Turkoğlu, 2010; Graf, 1992). Accumulating data suggested that saponins with oleanan and cycloartan skeleton isolated from Astragalus species showed a variety of biological activities such as antiviral (Gariboldi, 1995), immunostimulant (Bedir vd., 2000c; Çalış vd., 1997; Yeşilada vd., 2005; Nalbantsoy vd., 2011), immunostimulants cardiotonic (Khushbaktova vd., 1994), cytotoxic (Radwan vd., 2004), anti-protozoal (Özipek vd., 2005) and wound healing (Sevimli-Gür vd., 2011) effects. Many oleanan and cycloartan type triterpene saponins from Astragalus species were isolated and these compounds were investigated with their immunostimulant, anti-protozoal, anti-cancer, cytotoxic activity as well as their haemolysis effects by our group (Çalış vd., 1997; Bedir vd., 1998, 1999a,1999b; Çalış vd., 1997; Çalış vd., 2008; Denizli vd., 2014; Gülcemal vd., 2011, 2012, 2013; Horo vd., 2010, 2012; Polat vd., 2009, 2010; Savran vd., 2012; Denizli vd., 2014). In vitro and in vivo studies on Astragalus saponins showed that these groups of compounds were significantly able to induce the levels of IL-2 (Nalbantsoy et al., 2012, 2011; Yeşilada et al., 2005). It was also reported that Astragalus extracts were used as immune system-stimulating drugs (Graf, 1992). There are no studies regarding to phytochemical and/or immunomodulatory effects of Iranian Astragalusto date. Therefore, it was aimed to carry out further studies on Astragalus species from Iran / Iran-Turan regions and discover their immunomodulatory activities in the current thesis a few Astragalus species gathered from Iran. In total, 37 compounds were isolated from 3 different Astragalus plants and 4 of these compoundsThe effects of the extracts and some compounds on the immune system were investigated in terms of their effect on the release of immunomodulatory cytokines using human blood and their hemolytic activities against human erythrocytes. Tested extracts and compounds (at doses of 3 2,5g and 6 veg) significantly increased IL-2, IL-17A and INF-? cytokine release, In this study, 22 Iran-Turan Astragalus species were investigated phytochemically by using thin-layer chromatography and 3 Astragalus species (Astragalus brachycalyx FISCHER, Astragalus carjaginii BORISS, Astragalus leiophyllus FREYN & BORNM), which were rich in saponins, were chosen for the current study and NMR was performed using ESI-MS and HR-MS. In total, 37 molecules were isolated from 3 different Astragalus plants of which 4 mollecules were found to be newly identified (3-O-?-D-xylopyranosyl-6-O-?-D-glucopyranosyl-16-O-?-D-glucopyranosyl-3?, 6?, 16? , 24 (S), 25-pentahydroxycycloartane, 3-O- [?-L-arabinopyranosyl- (1 ? 2) -?-D-xylopyranosyl] -6-O-?-D-glucopyranosyl-16-O-?- Dglucopyranosyl-3?, 6?, 16?, 24 (S), 25-pentahydroxycycloartane, 6?, 16?, 24 (S), 25-tetrahydroxy-cycloartan-3-one and 6-O-?-D-xylopyranosyl-3?, 6?, 16?, 24 (S), 25-pentahydroxycycloartane). The effects of the extracts and some molecules on the immune system were investigated in terms of their effect on the release of immunomodulatory cytokines using human blood and their hemolytic activities against human erythrocytes. The tested extracts and molecules showed significantly positive effects on cytokine release (IL-2, IL-17A and INF-?) while tested extracts and compounds (2,5, 12,5, 25, 50, 125, At 250, 500, 5000 ?g / mL) did not cause any hemolysis.
Açıklama
Anahtar Kelimeler
Biyoteknoloji, Biotechnology
