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.