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Türkiye'de yetişen pinus türleriyle ilgili farmakognostik çalışmalar
Current environmental factors and lifestyles deteriorate the balance of oxidants and antioxidants, and hence, oxidative stress and various diseases trigger in the human body. Substantial evidence suggests that oxidative stress is associated directly with diabetes and its microvascular and cardiovascular complications. Numerous scientific research has indicated that natural products could prevent the body from oxidative stress and alleviate many oxidative stress-related diseases. Pycnogenol®, a patented-standardized extract from P. pinaster barks, is one of the pharmacologically active natural products. This thesis was planned to evaluate the phytochemical profile, antioxidant and anti-diabetic activities of hot water extracts from the barks of two naturally growing Pinus species in Turkey; P. brutia Ten., P. pinea L., and one cultivated species in Turkey; P. pinaster Ait. Their chemical and activity profiles were compared to Pycnogenol® before and after submitting to an in vitro gastrointestinal human digestion simulation system. In vitro antioxidant assays indicated that hot water bark extracts of all studied plants possess high antioxidant activity in terms of free radical scavenging, metal-reducing activity, and total antioxidant activity. In addition, the results showed that all studied extracts had potent inhibitory activities on α-glucosidase, α-amylase enzymes and advanced-glycation end products (AGEs). The total phenolic, phenolic acid, proanthocyanidin, and flavonoid contents and also the amounts of some proanthocyanidins (proanthocyanidin A1, a proanthocyanidin B1/B2 mixture, proanthocyanidin C1), and flavan-3-ol derivatives (catechin/epicatechin mixture, epigallocatechin, epigallocatechin gallate, and catechin gallate), and several other phenolic components (taxifolin, caffeic acid, and ferulic acid) were measured to reveal the phytochemical contents of all studied extracts. High Performance Thin Layer Chromatography (HPTLC) system was used to identify and quantify of these metabolites. The results indicated that even though in vitro human gastrointestinal system negatively influenced the phytochemical profile, antioxidant and anti-diabetic potentials, all extracts possess high phenolic content and potent biological activities. Key words: Pinus species, Phenolic compounds, Antioxidant activity, In vitro Gastrointestinal Digestion Simulation system, HPTLC, Antidiabetic Activity
Antidiyabetik etkili bitki çayı formülü geliştirilmesi
Diyabet, eski çağlardan beri bilinen ve yaygın rastlanan kronik metabolik bir hastalıktır. Dünya Sağlık Örgütünün açıklamalarına göre önümüzdeki yıllarda insanların ölüm nedenleri arasında ilk sıralarda yer alacağı öngörülmüştür. Türkiye'de de sıklıkla rastlanan diyabetli hasta sayısının toplam nüfusun %15'i kadar olduğu düşünülmektedir. Hastalık ömür boyu ilaç tedavisi gerektirdiğinden olası ilaçların olası yan etkileri ve yüksek maliyetli oluşu hastaların doğal tedavi yöntemleri arayışına girmesine sebep olmuştur. Hastaların doğal tedavi tercihleri incelendiğinde ise en çok bitki çayı tüketimine yöneldikleri görülmüştür. Antidiyabetik etkisiyle eski çağlardan günümüze kadar en yaygın kullanılan seçeneklerin başında zeytin yaprağı çayı gelmektedir. Fakat antidiyabetik etkisinden sorumlu olduğu düşünülen sekonder metabolitlerinden oleuropein bir sekoiridoit bileşik olduğu için acı tada sahiptir. Bu çalışmada zeytin yaprağı çayını bal ya da şeker ilavesi gerektirmeden diyabet hastaları tarafından rahatça tüketebilecek, yumuşak içimli bir şekle getirmek amaçlandı. Aynı zamanda antidiyabetik etkisini de kaybetmemesi göz önünde bulundurularak yapılan literatür çalışmaları sonucu zeytin yaprağı çayına; Seylan tarçını kabuğu, beyaz dut yaprağı, stevya yaprağı ve kurt üzümü meyvesi ilave edilerek 3 ayrı bitki çayı formülü oluşturuldu. Oluşturulan 3 ayrı karışık bitki çayı formülü ile tek drogdan oluşan zeytin yaprağı çayının fenolik içerik, antioksidan profil ve glikoz enzim inhibisyonları açısından in vitro deney çalışmaları yapılıp elde edilen veriler karşılaştırıldı. Sonuç olarak; antidiyabetik ve antioksidan etkisi bakımından zeytin yaprağı çayına yakın sayılabilecek değerlerde ölçüm sonuçları veren aynı zamanda diyabet hastalarının şeker ya da bal ilave etmek zorunda kalmadan rahatça tüketebileceği düşünülen yumuşak içimli bitki çayı formüllerine ulaşıldı.
Gentiana asclepiadea ve G. cruciata'dan sekonder metabolitlerin izolasyonu, antienflamatuvar ve analjezik aktivitelerinin araştırılması
Chronic inflammatory diseases account for nearly half of all deaths worldwide and the potential adverse effects of current treatment protocols necessitate to develop safer alternatives. Over recent years, plant extracts and plant-derived drugs have gained more attention as natural therapeutic agents. Members of the genus Gentiana have long been used for the prevention and treatment of a wide variety of diseases. Extracts obtained from this genus, as well as the isolates, were reported to possess anti-inflammatory and analgesic activities according to the latest findings. The aim of this thesis was to purify the compounds from the MeOH extracts prepared from the aerial parts of Gentiana asclepiadea L. and G. cruciata L. and to evaluate their in vitro anti-inflammatory and analgesic activities. A new secoiridoid glycoside, cruciatoside (1), along with ten known compounds, eustomoside (2), eustomorusside (3), gentiopicroside (5), 6'-O-β-D-glucosyl gentiopicroside (6), loganic acid (7), isoorientin (8), isovitexin (9), isovitexin 2''-(E)-ferulate (10), mangiferin (11) and 2-methyl inositol (13) were isolated from G. cruciata, while depressine (4), compounds 5, 7-9, 11 and adenosine (12) were obtained from G. asclepiadea. The structures were elucidated mainly by HR-MS, 1D and 2D NMR experiments. The anti-inflammatory activities of the isolated compounds were evaluated through nitrite and IL-6 levels in RAW 264.7 cells activated by LPS. Among all the tested compounds, 10 exerted the most potent nitrite inhibition with 39.5% rate at 200 μM, comparable to positive control indomethacin. Also, compounds 4, 5, and 8 exhibited a moderate nitrite inhibition over 20%. On the other hand, 4 showed the highest decrease in IL-6 levels among all the tested compounds, which was followed by compounds 5, 8 and 1, respectively. Compounds 4 and 5 displayed the most potent in vitro analgesic activity by decreasing PGE2 secretion from LPS-activated RAW264.7 cells, comparable to the positive control, indomethacin. Consequently, compounds 1, 4, 5, 8, and 10 were determined as potent anti-inflammatory and analgesic agents, which deserve further in vitro and in vivo investigations.
Farklı sabit yağlarda güneşte maserasyon tekniğiyle hazırlanan hypericum perforatum L. oleatlarının yara iyileştirici etkisinin farmakolojik ve analitik yöntemlerle karşılaştırması
St.John's wort (Hypericum perforatum L.) has been recognized as one of the most popular medicinal plants worldwide. Among a wide range of healing benefits wound healing effect of its oleates in various edible fixed oils, particularly in raw olive oil, have been used traditionally for centuries externally in wound healing (wounds, scars, etc.) or orally for the treatment of peptic ulcer. Although the wound healing effect of various types of H. perforatum oleates prepared in edible fixed oils, i.e., in olive (Olea europaea) oil, sesame (Sesamum indicum) seed oil, sunflower (Helianthus annuus) oil, and black seed (Nigella sativa) oil, have been proven both by experimental and clinical studies, efficiency of these oleates in wound healing has not been comparatively investigated so far. This experimental study aimed to reveal the wound healing potencies of H. perforatum oleates in various edible oils (olive oil, sesame seed oil, sunflower oil, and black seed oil) comparatively, both in analytical and pharmacological means. Firstly, quality specifications of the edible fixed oils used in maceration were analyzed by GC-MS chromatography, and the specific marker components (i.e., oleuropein in olive oil and thymoquinone in black seed oil) were determined by HPLC or sesamin and sesamol were measured by UV spectroscopy in sesame seed oil. Then macerates were prepared with the traditional sun maceration technique. The amounts of the main active components, namely hypericin, hyperforin, and pseudohypericin, were determined by LC-MS and UV methods. Since fixed oils have also known to possess some wound healing activity in vitro and in vivo studies were conducted to determine the wound healing effects of both the fixed oils and the oleates comparatively. The results demonstrated that the wound-healing activity of all oleates were significantly higher comparing to that of the fixed oils used as vehicle. In vivo experiments showed that oleates in olive oil and sesame oil provided the best synergetic effects among the others.