Prunus laurocerasus L. Meyve Ekstraktının Sıçanlarda İndometazin ile İndüklenen Gastrik Ülsere Karşı Koruyucu Etkisi

Yıl 2019, Cilt: 14 Sayı: 1, 64 - 70, 28.04.2019

Hamit Uslu , Gözde Atila Uslu

https://doi.org/10.17094/ataunivbd.450513

Öz

Bu çalışmada Prunus laurocerasus meyve ekstraktının, non-steroid antiinflamatuar ilaçlardan biri olan indometazin kaynaklı gastrik ülser modelinde koruyucu etkilerinin araştırılması amaçlanmıştır. Deney hayvanları dört gruba ayrıldı (Kontrol, Prunus laurocerasus, İndometazin ve Omeprazol grupları). I. ve III. gruba izotonik tuzlu su, II. gruba 500 mg/kg Prunus laurocerasus ekstraktı ve IV. gruba 5 mg/kg omeprazol oral olarak verildi. Çalışmanın 11. gününde II, III ve IV. gruplara tek doz 100 mg/kg indometazin oral olarak uygulandı. Siklooksijenaz - 2 (COX-2) ve C - reaktif protein (CRP) seviyeleri, indometazin grubunda önemli şekilde artarken (P<0.001), Prunus laurocerasus (sırasıyla P<0.05, P<0.001) ve omeprazol uygulamaları ile önemli şekilde azaldı (sırasıyla P<0.01, P<0.001). İndometazin grubunda interlökin - 6 (IL-6) ve tümör nekrozis faktör - alfa (TNF-α) düzeylerinde artış olduğu belirlendi (P<0.05). Hem Prunus laurocerasus hem de omeprazol uygulaması ile IL-6 ve TNF-α düzeylerinin azaldığı, ancak bu azalışların istatistiksel olarak anlamlı olmadığı tespit edildi. Sonuç olarak, Prunus laurocerasus’un, mide ülserinde CRP ve COX-2 seviyelerini düşürmede piyasadaki standart ilaçlardan biri olan omeprazol benzeri etki gösterdiği tespit edilmiştir.

Anahtar Kelimeler

C-reaktif protein, Gastrik ülser, Prunus laurocerasus, Proinflamatuar sitokinler, Siklooksigenaz-2

Protective Effect of Prunus laurocerasus L. Fruit Extract Against Indomethacin-Induced Gastric Ulcer in Rats

Öz

In the present study, it was aimed to investigate the protective effects of Prunus laurocerasus fruit extract in the indomethacine-induced gastric ulcer model, which one of the non-steroid anti-inflammatory drugs. Experimental animals were divided into four groups (Control, Prunus laurocerasus, Indomethacine and Omeprazole groups). The groups I and III was given isotonic saline, the group II was given 500 mg/kg Prunus laurocerasus extract and the group IV was given 5 mg/kg omeprazole orally. On the 11th day of the study, a single dose of 100 mg/kg indomethacine was administered orally to the II, III and IV groups. The levels of cyclooxygenase - 2 (COX-2) and C - reactive protein (CRP) increased significantly in indomethacine group (P<0.001), while significantly decreased with the application of Prunus laurocerasus (P<0.05, P<0.001 respectively) and omeprazole (P<0.01, P<0.001 respectively). It was determined that interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were increased in the indomethacin group (P<0.05). It was detected that IL-6 and TNF-α levels decreased with both Prunus laurocerasus and omeprazole administration, but these decreases were not statistically significant. In conclusion, it has been detected that Prunus laurocerasus has an omeprazole-like effect, which is one of the standard drugs in the market, when lowering CRP and COX-2 levels in gastric ulcer.

Anahtar Kelimeler

Gastric ulcer, Prunus laurocerasus, Proinflammatory cytokines, C - reactive protein, Cyclooxygenase - 2, Prunus laurocerasus

Kaynakça

• 1 Shim YK., Kim N., 2016. Nonsteroidal anti-inflammatory drug and aspirin-induced peptic ulcer disease. Korean J Gastroenterol, 67, 300–312.
• 2 Cheng YT., Lu CC., Yen GC., 2017. Phytochemicals enhance antioxidant enzyme expression to protect against NSAID‐induced oxidative damage of the gastrointestinal mucosa. Mol. Nutr. Food Res, 61(6), 1600659.
• 3 Sonnenberg A., 1996. Geographic andtemporal variations inthe occurrence of peptic ulcer disease. Scand J Gastroenterol Suppl, 110, 11.
• 4 Shristi B., Neha J., Indu BP., Rajesh G., 2012. A review on some Indian medicinal plants for antiulcer activity. J Sci Res Pharm, 1, 6–9.
• 5 Wallace JL., 2001. Pathogenesis of NSAID-induced gastroduodenal mucosal injury. Best Pract Res Clin Gastroenterol, 15, 691–703.
• 6 Griffin MR., Scheiman JM., 2001. Prospects for changing the burden of nonsteroidal anti-inflammatory drug toxicity. Am J Med, 110, 33S–37S.
• 7 Antonisamy P., Arasu MV., Dhanasekaran M., Choi KC., Aravinthan A., Kim NS., 2016. Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms. Food & function, 7(1), 398–408.
• 8 Tegeder I., Neupert W., Guhring H., Geislinger G., 2000. Effects of selective and unselective cyclooxygenase inhibitors on prostanoid release from various rat organs. J Pharmacol Exp Ther, 292, 1161–1168.
• 9 Mitchell JA., Larkin S., Williams TJ., 1995. Cyclooxygenase-2: regulation and relevance in inflammation. Biochem. Pharmacol, 50, 1535–1542.
• 10 Vavilov NI., 1951. The origin, variation, immunity and breeding of cultivated plants. 72(6), 482.
• 11 Elmastas M., Genc N., Demirtas I., Aksit H., Aboul-Enien HY., 2013. Isolation and Identification of Functional Components in Seed of Cherry Laurel (Laurocerasus officinalis Roem.) and Investigation of Their Antioxidant Capacity. TBAP, 3(2), 115–120.
• 12 Alasalvar C., Al‐Farsi M., Shahidi F., 2005. Compositional characteristics and antioxidant components of cherry laurel varieties and pekmez. Journal of food science, 70(1), S47–S52.
• 13 Ozturk B., Celik SM., Karakaya M., Karakaya O., Islam A., Yarilgac T., 2017. Storage temperature affects phenolic content, antioxidant activity and fruit quality parameters of cherry laurel (Prunus laurocerasus L.). J Food Process Preserv, 41(1), e12774.
• 14 Uslu H., Atila Uslu G., Özen H., Karaman M., 2018. Effects of different doses of Prunus laurocerasus L. leaf extract on oxidative stress, hyperglycaemia and hyperlipidaemia induced by type I diabetes. IJTK, 17(3), 430–436.
• 15 Ustun NS., 2003. A Research on Composition of Wild Cherry Laurel (Laurocerasus officinalis Roem). Journal of Food Technology, 1(2), 80–82.
• 16 Kolayli S., Kucuk M., Duran C., Candan F., Dincer B., 2003. Chemical and antioxidant properties of Laurocerasus officinalis Roem. (cherry laurel) fruit grown in the Black Sea region. J. Agric. Food Chem, 51(25), 7489–7494.
• 17 Özbakiş-Dengiz G., Hekimoğlu A., Kandemir N., Kurcer Z., 2012. Effects of statins in an indomethacin-induced gastric injury model in rats. Turk J Gastroenterol, 23(5), 456–462.
• 18 Shigeta JI., Takahashi S., Okabe S., 1998. Role of cyclooxygenase-2 in the healing of gastric ulcers in rats. JPET, 286(3), 1383–1390.
• 19 Inas ZA., Hala AK., Gehan HH., 2011. Gastroprotective effect of Cordia myxa L. fruit extract against indomethacin-induced gastric ulceration in rats. Life Sci J, 8(3), 433–445.
• 20 Shimizu N., Watanabe T., Arakawa T., Fujiwara Y., Higuchi K., Kuroki T., 2000. Pentoxifylline accelerates gastric ulcer healing in rats: Roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing. Digestion, 61(3), 157–164.
• 21 Alkushi AGR., Elsawy NAM., 2017. Quercetin attenuates, indomethacin-induced acute gastric ulcer in rats. Folia morphologica, 76(2), 252–261.
• 22 Langman MJ., Weil J., Wainwright P, Lawson, DH., Rawlins MD., Logan RFA., et al. 1994. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet, 343, 1075–1078.
• 23 Su SC., Hua KF., Lee H., Chao LK., Tan SK., Lee H., et al. 2006. LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages. Clin Chim Acta, 374, 106–115.
• 24 Appleyard CB., McCafferty DM., Tigley AW., Swain MG., Wallace JL., 1996. Tumor necrosis factor mediation of NSAID-induced gastric damage: Role of leukocyte adherence. Am J Physiol, 270, G42–G48.
• 25 Kurt H., Özbayer C., Değirmenci İ., Burukoğlu D., Saadat SM., Üstüner MC., et al. 2016. İndomethazine Bağlı Oluşan Gastrik Mukozal Hasar Üzerine Hypericum Perforatum Yağının Koruyucu Etkisi. Bozok Tıp Derg, 6(3), 62–68.
• 26 Lim HY., Joo HJ., Choi JH., Yi JW., Yang MS., Kim HS., et al. 2000. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. CCR, 6(2), 519–525.
• 27 Tucker ON., Dannenberg AJ., Yang EK., Zhang F., Teng L., Daly JM., et al. 1999. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. CR, 59(5), 987–990.
• 28 Zhang Y., 2013. Impact of esomeprazole on gastrointestinal hormones and inflammatory state of patients with gastric ulcer. Journal of Clinical Medicine in Practice, 17, 68–70.
• 29 Boehme MW., Autschbach F., Ell C., Raeth U., 2007. Prevalence of silent gastric ulcer, erosions or severe acute gastritis in patients with type 2 diabetes mellitus ‑ a cross‑sectional study. Hepatogastroenterology, 54, 643–648.
• 30 Liyana-Pathirana CM., Shahidi F., Alasalvar C., 2006. Antioxidant activity of cherry laurel fruit (Laurocerasus officinalis Roem.) and its concentrated juice. Food Chemistry, 99(1), 121–128.
• 31 Karabegović IT., Stojičević SS., Veličković DT., Nikolić NČ., Lazić ML. 2013. Optimization of microwave-assisted extraction and characterization of phenolic compounds in cherry laurel (Prunus laurocerasus) leaves. Sep. and Pur. Tech, 120, 429–436.
• 32 Celep E., Aydın A., Yeşilada E., 2012. A comparative study on the in vitro antioxidant potentials of three edible fruits: Cornelian cherry, Japanese persimmon and cherry laurel, Food Chem Toxicol, 50, 3329–3335.
• 33 Orhan IE., Akkol EK., 2011. Estimation of neuroprotective effects of Laurocerasus officinalis Roem. (cherry laurel) by in vitro methods, Food Res. Int, 44, 818–822.
• 34 Orhan N., Damlaci T., Baykal T., Özek T., Aslan M., 2015. Hypoglycaemic Effect of Seed and Fruit Extracts of Laurel Cherry in Different Experimental Models and Chemical Characterization of the Seed Extract. Rec. of Nat. Prod, 9(3), 379.
• 35 Karahalil FY., Sahin H., 2011. Phenolic composition and antioxidant capacity of cherry laurel (Laurocerasus officinalis Roem.) sampled from Trabzon region, Turkey. Afr. J. Biotechnol, 10(72), 16293–16299.