CELAL GÜVEN, EYLEM TAŞKIN GÜVEN, ÖNDER YUMRUTAŞ, LEYLA TÜRKER ŞENER, FULYA DAL, Mufide AHBAB, İBRAHİM BOZGEYİK, IŞIL ALBENİZ, HAYDAR BAĞIŞ, MUSTAFA PEHLİVAN, Fatih ÜÇKARDEŞLER, HANDAN AKÇAKAYA

Streptozotosin Uygulanan İnsan Pankreatik  Hücre Soyu (1.1b4) Üzerine Leontice Leontopetalum Ekstratının Antidiyabetik Etkisinin Araştırılması

Yapılan araştırmalarda Berberidace familyasına ait bazı bitkilerin şeker hastaları tarafından kullanıldığı tespit edilmiştir. Leontice leontopetalum (LL), bu familyaya ait bir bitki türüdür. LL ekstratının, diyabet oluşturulmuş insan pankreatik β hücre soyu (1.1B4) üzerindeki antidiyabet etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: 10 ve 20 mM streptozotosin (STZ) uygulamalarıyla diyabet oluşturulan insan pankreatik beta hücrelere (1.1B4); 0, 1, 10, 100, 1000 g/ml dozlarındaki LL ekstratları 24 saat boyunca uygulanmıştır. Hücre canlılığı, gerçek zamanlı hücre proliferasyon analizi (xCelligence), glukoz (1,1, 8,4, 16,7 mM) ile indüklenmiş insülin salınım ve içeriği hücre soylarında belirlenmiştir. Bulgular: MTT analizi sonucunda, 1.1B4 hücreleri üzerinde 24 saatlik uygulamada tüm gruplarda LL ekstratın dozu arttıkça hücre canlılığında doza bağımlı azalma gözlenmiştir. Gerçek zamanlı hücre proliferasyonu analiz sonuçlarında hücre proliferasyonunun STZ dozuna bağımlı olarak azaldığı, Leontice leontopetalum’un en düşük ve yüksek dozlarında azalma olduğu, yine aynı şekilde STZ ile birlikte Leontice leontopetalum uygulanan tüm gruplarda da azalma tespit edilmiştir. Glukoz ile indüklenmiş insülin salınım sonuçlarında, STZ dozuna bağımlı olarak açlık ve en yüksek glukoz konsantrasyonlarında insülinin hücre içeriğinin azaldığı, STZ ile birlikte LL uygulamalarda doza bağımlı insülin içeriğinin azaldığı bulunmuştur. Sonuç olarak Leontice leontopetalum tedavisininin, diyabetik beta hücrelerde insülin içeriğini azaltması, insülinin salınımını arttırdığı; fakat hücre canlılığı üzerine olumsuz etkilerinin olduğu sonucuna varılmıştır.

The Investigation of Antidiabetic Effects of Leontice leontopetalum Extract on Human Pancreatic β Cell Lines (1.1B4) Treated with Streptozotocin A R T I C L E I N F O

One of the alternative therapeutic methods is herbal medicine. Leontice leontopetalum belongs to Berberidaceae family. The aim of study was investigated the extract of LL on human pancreatic beta cell-treated with STZ. Materials and methods: The human pancreatic beta cell (1.1B4) line was used the current study. LL’s extracts (1, 10, 100, and 1000 ug/ml) were supplemented in media for twenty-four hours and/or after STZ treatment (10 and 20 mM). Cells survivals (MTT), cells proliferation were shown by using xCelligence. Insulin content and releasing were measured at 1.1, 8.4 and 16.7 mM glucose concentrations. Results: The result of MTT was shown that cell survival was decreased, based on dose-dependent. When looked at xCelligence results, cell proliferation in STZ groups and the lowest and highest concentrations of LL were attenuated in a dose-dependent manner. Also, cotreatments of LL and STZ were decreased as well. The result of insulin-releasing on glucose induction was shown that STZ concentration gave rise to reduce insulin content at low and high glucose levels. Also, co-treatment of LL and STZ attenuated insulin content based on dose. Conclusion: It was considered that LL treatment led to increased insulin realizing, resulting from decreasing insulin content in diabetic beta cells, but decrease cell survival.

PDF

___

Abdalla S, Abu-Zarga M, Sabri S.1989. Preliminary observations on the pharmacology of petaline chloride, a quaternary alkaloid from Leontice leontopetalum. Gen Pharmacol 20(5):565-9
Ahmad K, Lewis JJ. 1960. On the pharmacology of petaline chloride, a convulsant alkaloid from Leontice leontopetalum Linn. J Pharm Pharmacol 12:163-74
Alam U, Asghar O, Azmi S, Malik RA. 2014. General aspects of diabetes mellitus. Handb Clin Neurol 126:211-22 doi:10.1016/B978-0-444-53480-4.00015-1
American Diabetes A. 2009. Diagnosis and classification of diabetes mellitus. Diabetes Care 32 Suppl 1:S62-7 doi:10.2337/dc09-S062
American Diabetes A. 2013. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 36(4):1033-46 doi:10.2337/dc12-2625
Buldak L, Dulawa-Buldak A, Labuzek K, Okopien B. 2012.Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Int J Clin Pharmacol Ther 50(11):805-13 doi:10.5414/CP201735
Chang AY, Perry CS. 1978. Acid glycohydrolase in Chinese hamster with spontaneous diabetes. IV. Diabetes- and linedependent variation in plasma enzyme activity. Diabetologia 15(5):423-9
Dickson LM, Rhodes CJ. 2004. Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt? Am J Physiol Endocrinol Metab 287(2):E192-8 doi:10.1152/ajpendo.00031.2004
Dunn JS, Duffy E, Gilmour MK, Kirkpatrick J, McLetchie NG. 1944. Further observations on the effects of alloxan on the pancreatic islets. J Physiol 103(2):233-43
Ejrnaes M, von Herrath MG, Christen U. 2006. Cure of chronic viral infection and virus-induced type 1 diabetes by neutralizing antibodies. Clin Dev Immunol 13(2-4):337-47 doi:10.1080/17402520600800721
Fish F, Nelson PF. 1956. Studies on Leontice leontopetalum Linn. II. History, sources and macroscopical characters of the plant L. leontopetalum. J Pharm Pharmacol 8(12):1134- 42
Gulcin I, Mshvildadze V, Gepdiremen A, Elias R. 2006. Screening of antiradical and antioxidant activity of monodesmosides and crude extract from Leontice smirnowii tuber. Phytomedicine 13(5):343-51 doi:10.1016/j.phymed.2005.03.009
Gushiken LF, Beserra FP, Rozza AL, Bergamo PL, Bergamo DA, Pellizzon CH. 2016. Chemical and Biological Aspects of Extracts from Medicinal Plants with Antidiabetic Effects. Rev Diabet Stud 13(2-3):96-112 doi:10.1900/RDS.2016.13.96
Guven C, Dal F, Aydogan Ahbab M, et al. 2016. Low dose monoethyl phthalate (MEP) exposure triggers proliferation by activating PDX-1 at 1.1B4 human pancreatic beta cells. Food Chem Toxicol 93:41-50 doi:10.1016/j.fct.2016.04.023
Harel A, Bloch O, Vardi P, Bloch K. 2002. Sensitivity of HaCat keratinocytes to diabetogenic toxins. Biochem Pharmacol 63(2):171-8
Herr RR, Eble TE, Bergy ME, Jahnke HK. 1959. Isolation and characterization of streptozotocin. Antibiot Annu 7:236-40
Imaeda A, Kaneko T, Aoki T, et al. 2002. Antioxidative effects of fluvastatin and its metabolites against DNA damage in streptozotocin-treated mice. Food Chem Toxicol 40(10):1415-22
Ishihara H, Maechler P, Gjinovci A, Herrera PL, Wollheim CB. 2003. Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat Cell Biol 5(4):330-5 doi:10.1038/ncb951
Kaya ST, Bozdogan O, Ozarslan TO, et al. 2018. The protection of resveratrol and its combination with glibenclamide, but not berberine on the diabetic hearts against reperfusioninduced arrhythmias: the role of myocardial KATP channel. Arch Physiol Biochem:1-8 doi:10.1080/13813455.2018.1440409
Kocahan S, Dogan Z, Erdemli E, Taskin E. 2017. Protective Effect of Quercetin Against Oxidative Stress-induced Toxicity Associated With Doxorubicin and Cyclophosphamide in Rat Kidney and Liver Tissue. Iran J Kidney Dis 11(2):124-131
Kotha P, Badri KR, Nagalapuram R, Allagadda R, Chippada AR. 2017. Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin Induced Diabetic Rats. Cell Physiol Biochem 43(4):1689-1702 doi:10.1159/000484030
Lopez Lopez R, Fuentes Garcia R, Gonzalez-Villalpando ME, Gonzalez-Villalpando C. 2017. Diabetic by HbA1c, Normal by OGTT: A Frequent Finding in the Mexico City Diabetes Study. J Endocr Soc 1(10):1247-1258 doi:10.1210/js.2017- 00266
Melikoglu G, Cubukcu B, Sariyar G. 2007. Flavonoids of Artemisia araratica. Nat Prod Res 21(8):767-8 doi:10.1080/14786410601130646
Molina J, Rodriguez-Diaz R, Fachado A, Jacques-Silva MC, Berggren PO, Caicedo A. 2014. Control of insulin secretion by cholinergic signaling in the human pancreatic islet. Diabetes 63(8):2714-26 doi:10.2337/db13-1371
Moonschi FH, Hughes CB, Mussman GM, Fowlkes JL, Richards CI, Popescu I. 2017. Advances in micro- and nanotechnologies for the GLP-1-based therapy and imaging of pancreatic beta-cells. Acta Diabetol doi:10.1007/s00592- 017-1086-7
Oh YS, Jun HS. 2017. Effects of Glucagon-Like Peptide-1 on Oxidative Stress and Nrf2 Signaling. Int J Mol Sci 19(1) doi:10.3390/ijms19010026
Ota A, Ulrih NP. 2017. An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes. Front Pharmacol 8:436 doi:10.3389/fphar.2017.00436
Ozaykan B, Taskin E, Magemizoglu A. 2017 Effect of salt loading on baroreflex sensitivity in reduced renal mass hypertension. Clin Exp Hypertens 39(7):592-600 doi:10.1080/10641963.2017.1299748
Pathak V, Vasu S, Flatt PR, Irwin N. 2014. Effects of chronic exposure of clonal beta-cells to elevated glucose and free fatty acids on incretin receptor gene expression and secretory responses to GIP and GLP-1. Diabetes Obes Metab 16(4):357-65 doi:10.1111/dom.12227
Raza H, John A. 2012. Streptozotocin-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in human hepatoma HepG2 cells. Int J Mol Sci 13(5):5751-67 doi:10.3390/ijms13055751
Saini KS, Thompson C, Winterford CM, Walker NI, Cameron DP. 1996. Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic beta cell line, INS-1. Biochem Mol Biol Int 39(6):1229-36
Takada J, Machado MA, Peres SB, et al. 2007. Neonatal streptozotocin-induced diabetes mellitus: a model of insulin resistance associated with loss of adipose mass. Metabolism 56(7):977-84 doi:10.1016/j.metabol.2006.05.021
Taskin E, Guven C, Sahin L, Dursun N. 2016. The Cooperative Effect of Local Angiotensin-II in Liver with Adriamycin Hepatotoxicity on Mitochondria. Med Sci Monit 22:1013-21
Taskin E, Tuncer KA, Guven C, Kaya ST, Dursun N. 2016. Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia. Med Sci Monit 22:4587-4595
Tozzo E, Gnudi L, Kahn BB. 1997 Amelioration of insulin resistance in streptozotocin diabetic mice by transgenic overexpression of GLUT4 driven by an adipose-specific promoter. Endocrinology 138(4):1604-11 doi:10.1210/endo.138.4.5043
Vashum KP, McEvoy M, Milton AH, Islam MR, Hancock S, Attia J. 2014. Is serum zinc associated with pancreatic beta cell function and insulin sensitivity in pre-diabetic and normal individuals? Findings from the Hunter Community Study. PLoS One 9(1):e83944 doi:10.1371/journal.pone.0083944
Zoffmann V, Kirkevold M. 2005. Life versus disease in difficult diabetes care: conflicting perspectives disempower patients and professionals in problem solving. Qual Health Res 15(6):750-65 doi:10.1177/1049732304273888