بررسی اثر بخشی عصاره کنگر فرنگی(Cynara scolymus L.)( فراورده طب سنتی ایران) بر شاخص های لیپیدپروفایل بیماران همودیالیزی در مقایسه با پلاسبو: کارآزمایی بالینی کنترل شده دوسوکور تصادفی


۲۱ شهریور ۱۳۹۶

مهمترین علت مرگ و میر بیماران مبتلا به نارسایی مزمن کلیه و بیماران همودیالیزی، بیماری های قلبی- عروقی می باشند. باتوجه به نقش فاکتورهای التهابی و هیپرلیپیدمی در ایجاد بیماری های قلبی-عروقی در بیماران همودیالیزی وعدم پژوهش در زمینه تاثیر مکمل کنگرفرنگی بر این عوامل، مطالعه حاضر با هدف مشخص نمودن اثرات این گیاه بر روی فاکتورهای لیپیدی و التهابی در بیماران همودیالیزی طراحی گردید.

روش کار:این مطالعه یک کارآزمایی بالینی شاهد دار تصادفی می باشد که نمونه ها در آن بیماران همودیالیزی با سابقه عدم کنترل چربی که حداقل 3 ماه از شروع دیالیز آن ها گذشته باشد می باشند. بیماران بطور تصادفی به دوگروه دریافت کننده فراورده کنگر فرنگی (320 میلی گرم روزی دو بار) یا دارونما اختصاص داده شدند.در هردوگروه ، قرص آتورواستاتین به طور روتین دریافت شد.کاهش سطح LDL سرمی پیامد اولیه و تغییرات سطح تری گلیسرید، کلسترول توتال، HDL، ESR،CRPو سطوح فریتین و آهن سرم و TIBCپیامدهای ثانویه در این طرح می باشند.

نتايج:درصد کاهش غلظت LDL در پایان مطالعه در گروه مداخله نسبت به گروه کنترل بیشتر بود .(P=0.001)درصد کاهش غلظت کلسترول توتال در پایان مطالعه در گروه مداخله نسبت به گروه کنترل بیشتر بود.(P=0.001)درصد کاهش غلظت تری گلیسرید در پایان مطالعه در گروه مداخله نسبت به گروه کنترل بیشتر بود.(p=0.007) دو گروه تفاوت معنی داری از نظر تغییرات سطح HDL نداشتند.میزان کاهش غلظت CRP و ESR در گروه مداخله بیشتر بود اما از نظر آماری معنی دار نبود (P>0.05).همچنین میزان سطح فریتین،آهن و TIBC در دو گروه تفاوت معنی داری نداشت.

نتيجه گيري:در مجموع ما دراین مطالعه برای نخستین بار نشان دادیم که کنگرفرنگی می تواند به عنوان درمانی موثر و ایمن جهت بهبود وضعیت هیپرلیپیدمی در بیماران مبتلا به نارسایی کلیه وابسته به همودیالیز مورد استفاده قرار گیرد. بعلاوه به نظر میرسد کنگرفرنگی اثرات سودمندی بر سطح مارکرهای التهابی همچون ESR و CRP داشته باشد.

 

كليد واژه ها کنگر فرنگی، نارسایی کلیه، همودیالیز، هیپرلیپیدمی:

مشخصات دانشجو:

نام: حنانه منقبتی       رشته تحصيلي:  پزشکی          مقطع: دکتری تخصصی            گروه آموزشي    داخلی        پست الكترونيك دانشجو:   hana.manghabati@gmail.com

اساتيد راهنما و داور:

استاد راهنما   دکتر سیدمنصور گتمیری و دکتر ابراهیم خادم ازغدی

  اساتيد مشاور مهندس محمد کمالی نژاد

  اساتيد داور دکتر اعظم علمداری و دکتر نرگس ساداتی

 

زمان دفاع :

   روز سه شنبه   تاريخ 14/6/96  ساعت 11 صبح

مكان دفاع به آدرس: بیمارستان امام خمینی. زیر ستونها.بخش دیالیز..اتاق رییس بخش دیالیز

اطلاعات به زبان انگليسي

Title: the effects of artichoke leaf extract (ALE) supplementation on the lipid pattern in the hemodyalisis patient

 

Abstract:

Background: Hypercholestrolemia and coronary artery diseases are among the most important causes of mortality in hemodialysis patients. The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation (320mg, 2 b.i.d.) on the lipid pattern.

 

Methods: A randomized, double-blind, placebo-controlled clinical trial was performed on 36 hemodialysis subjects with primary mild hypercholesterolaemia for 8 weeks. 18 subjects were randomized to supplementation and 18 subjects to placebo.

 

Results: ALE supplementation was associated with a significant decrease in mean Low-density

lipoprotein (LDL)-cholesterol ( p ,0.001).A significantly decreased difference was also found for the mean change in total cholesterol ( p,  0.001),low-density lipoprotein (LDL)-cholesterol ( p , 0.001), and triglyceride ( p , 0.007),when compared with placebo treatment. The two groups did not have a significant difference in High-density lipoprotein-cholesterol (HDL-C) level changes( p ,0.2)

 

Conclusions: These results indicate that ALE could play a relevant role in the management of mild hypercholesterolaemia in patients with end-stage renal disease (ESRD).

 

Keywords: artichoke leaf extract, ESRD, chlorogenic acid, cholesterol, dietary supplement, HDL cholesterol, luteolin

 

فهرست منابع و ماخذ فارسي و لاتين: 1.Perrone RD, Steinman TI, Beck GJ, Skibinski CI, Royal HD, Lawlor M, et al. Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1990;16(3):224-35.

2.Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461-70.

3.Levey AS, Greene T, Schluchter MD, Cleary PA, Teschan PE, Lorenz RA, et al. Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol. 1993;4(5):1159-71.

4.Mikolasevic I, Žutelija M, Mavrinac V, Orlic L. Dyslipidemia in patients with chronic kidney disease: etiology and management. International Journal of Nephrology and Renovascular Disease. 2017;10:35-45.

5.Kujawa-Szewieczek A, Więcek A, Piecha G. The lipid story in chronic kidney disease: a long story with a happy end? International Urology and Nephrology. 2013;45(5):1273-87.

6.Tu S-F, Chou Y-C, Sun C-A, Hsueh S-C, Yang T. The Prevalence of Metabolic Syndrome and Factors Associated with Quality of Dialysis among Hemodialysis Patients in Southern Taiwan. Global Journal of Health Science. 2012;4(5):53-62.

7.Ziai S, Dastpak A, Naghdi Badi H, PoorHoseini L, Hemati A. Review on Cynara scolymus L. Journal of Medicinal Plants. 2005;1(13):1-10.

8.Ceccarelli N, Curadi M, Picciarelli P, Martelloni L, Sbrana C, Giovannetti M. Globe artichoke as a functional food. Mediterranean Journal of Nutrition and Metabolism. 2010;3(3):197-201.

9.Burnham T, Hagemann R, Threlkeld D. The review of natural products-facts and comparisons. St Louis (MO): Wolters Kluwer Updated monthly. 1977.

10.Christaki E, Bonos E, Florou-Paneri P. Nutritional and functional properties of Cynara crops (Globe Artichoke and Cardoon) and their potential application: a review. International Journal of Applied Science and Technology. 2012;2(2).

11.Gebhardt R, Fausel M. Antioxidant and hepatoprotective effects of artichoke extracts and constituents in cultured rat hepatocytes. Toxicology in vitro : an international journal published in association with BIBRA. 1997;11(5):669-72.

12.Brenner B, Green J. Chronic renal failure. Harrison’s Principles of internal Medicine, Isselbacher KJ. McGraw-Hill, New York; 2005.

13.Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney international. 2011;80(1):17-28.

14.Hosseinpanah F, Kasraei F, Nassiri AA, Azizi F. High prevalence of chronic kidney disease in Iran: a large population-based study. BMC public Health. 2009;9(1):44.

15.Mahdavi-Mazdeh M. Why do we need chronic kidney disease screening and which way to go? Iranian journal of kidney diseases. 2010;4(4):275-81.

16.Thomas R, Kanso A, Sedor JR. Chronic Kidney Disease and Its Complications. Primary care. 2008;35(2):329-vii.

17.Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant. 2003;18(7):1272-80.

18.Tsimihodimos V, Mitrogianni Z, Elisaf M. Dyslipidemia Associated with Chronic Kidney Disease. The Open Cardiovascular Medicine Journal. 2011;5:41-8.

19.Betteridge DJ. What is oxidative stress? Metabolism. 2000;49(2 Suppl 1):3-8.

20.Davi G, Falco A, Patrono C. Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal. 2005;7(1-2):256-68.

21.Shao B, Heinecke JW. HDL, lipid peroxidation, and atherosclerosis. Journal of Lipid Research. 2009;50(4):599-601.

22.Adibhatla RM, Hatcher JF. Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies. BMB Rep. 2008;41(8):560-7.

23.Vaziri ND. Oxidative stress in uremia: nature, mechanisms, and potential consequences. Semin Nephrol. 2004;24(5):469-73.

24.Park CW. Niacin in patients with chronic kidney disease: Is it effective and safe? Kidney Research and Clinical Practice. 2013;32(1):1-2.

25.Staff TP. PDR for herbal medicines: Physician's Desk Reference (PDR); 2004.

26.Gebhardt R. Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Med Sci Monit. 2001;7 Suppl 1:316-20.

27.Colak E, Ustuner MC, Tekin N, Colak E, Burukoglu D, Degirmenci I, et al. The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats. SpringerPlus. 2016;5:216.

28.Jimenez-Escrig A, Dragsted LO, Daneshvar B, Pulido R, Saura-Calixto F. In vitro antioxidant activities of edible artichoke (Cynara scolymus L.) and effect on biomarkers of antioxidants in rats. J Agric Food Chem. 2003;51(18):5540-5.

29.Mocelin R, Marcon M, Santo GD, Zanatta L, Sachett A, Schönell AP, et al. Hypolipidemic and antiatherogenic effects of Cynara scolymus in cholesterol-fed rats. Revista Brasileira de Farmacognosia. 2016;26(2):233-9.

30.Li H, Xia N, Brausch I, Yao Y, Forstermann U. Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells. J Pharmacol Exp Ther. 2004;310(3):926-32.

31.Miccadei S, Di Venere D, Cardinali A, Romano F, Durazzo A, Foddai MS, et al. Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer. 2008;60(2):276-83.

32.Zhu XF, Zhang HX, Lo R. Antifungal activity of Cynara scolymus L. extracts. Fitoterapia. 2005;76(1):108-11.

33.Lopez-Molina D, Navarro-Martinez MD, Rojas Melgarejo F, Hiner AN, Chazarra S, Rodriguez-Lopez JN. Molecular properties and prebiotic effect of inulin obtained from artichoke (Cynara scolymus L.). Phytochemistry. 2005;66(12):1476-84.

34.Costabile A, Kolida S, Klinder A, Gietl E, Bauerlein M, Frohberg C, et al. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br J Nutr. 2010;104(7):1007-17.

35.Zapolska-Downar D, Zapolski-Downar A, Naruszewicz M, Siennicka A, Krasnodebska B, Koldziej B. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes. Life Sci. 2002;71(24):2897-08.

36.Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. Efficacy of Artichoke dry extract in patients with hyperlipoproteinemia. Arzneimittelforschung. 2000;50(3):260-5.

37.Wegener T, Fintelmann V. Pharmacological properties and therapeutic profile of artichoke (Cynara scolymus L.). Wiener medizinische Wochenschrift (1946). 1998;149(8-10):241-7.

38.Kulza M, Adamska K, Senczuk-Przybylowska M, Wozniak A, Wachowiak A, Miechowicz I, et al. [Artichoke--herbal drug]. Przegl Lek. 2012;69(10):1122-6.

39.Heidarian E, Rafieian-Kopaei M. Protective effect of artichoke (Cynara scolymus) leaf extract against lead toxicity in rat. Pharm Biol. 2013;51(9):1104-9.

40.Pittler MH, Thompson CO, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev. 2002(3):Cd003335.

41.Gebhardt R. Prevention of taurolithocholate-induced hepatic bile canalicular distortions by HPLC-characterized extracts of artichoke (Cynara scolymus) leaves. Planta Med. 2002;68(9):776-9.

42.Malekshah RE, Mahjub R, Rastgarpanah M, Ghorbani M, Partoazar AR, Mehr SE, et al. Effect of zeolite nano-materials and artichoke (Cynara scolymus L.) leaf extract on increase in urinary clearance of systematically absorbed nicotine. Arzneimittelforschung. 2012;62(12):650-4.

43.Fantini N, Colombo G, Giori A, Riva A, Morazzoni P, Bombardelli E, et al. Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats. Phytother Res. 2011;25(3):463-6.

44.Zhu X, Zhang H, Lo R. Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities. J Agric Food Chem. 2004;52(24):7272-8.

45.Llorach R, Espin JC, Tomas-Barberan FA, Ferreres F. Artichoke (Cynara scolymus L.) byproducts as a potential source of health-promoting antioxidant phenolics. J Agric Food Chem. 2002;50(12):3458-64.

46.Saenz Rodriguez T, Garcia Gimenez D, de la Puerta Vazquez R. Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine. 2002;9(8):687-93.

47.Azzini E, Bugianesi R, Romano F, Di Venere D, Miccadei S, Durazzo A, et al. Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads of Cynara scolymus L. (cultivar Violetto di Provenza) in human subjects: a pilot study. Br J Nutr. 2007;97(5):963-9.

48.Marakis G, Walker AF, Middleton RW, Booth JC, Wright J, Pike DJ. Artichoke leaf extract reduces mild dyspepsia in an open study. Phytomedicine. 2002;9(8):694-9.

49.Bundy R, Walker AF, Middleton RW, Wallis C, Simpson HC. Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial. Phytomedicine. 2008;15(9):668-75.

50.Petrowicz O, Gebhardt R, Donner M, Schwandt P, Kraft K. Effects of artichoke leaf extract (ALE) on lipoprotein metabolism in vitro and in vivo. Atherosclerosis. 1997;1(129):147.

51.Kusku-Kiraz Z, Mehmetcik G, Dogru-Abbasoglu S, Uysal M. Artichoke leaf extract reduces oxidative stress and lipoprotein dyshomeostasis in rats fed on high cholesterol diet. Phytother Res. 2010;24(4):565-70.

52.Ogier N, Amiot MJ, George S, Maillot M, Mallmann C, Maraninchi M, et al. LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia. Eur J Nutr. 2013;52(2):547-57.

53.Ghada Z, Saad TM. Effect of Cynara scolymus L.(artichoke) extract on lipid profile of hyperlipidemic male rats. Egyptian Journal of Hospital Medicine. 2009;37:733-41.

54.Kucukgergin C, Aydin AF, Ozdemirler-Erata G, Mehmetcik G, Kocak-Toker N, Uysal M. Effect of artichoke leaf extract on hepatic and cardiac oxidative stress in rats fed on high cholesterol diet. Biological trace element research. 2010;135(1-3):264-74.

55.Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. The Cochrane database of systematic reviews. 2013(3):Cd003335.

56.Rondanelli M, Giacosa A, Opizzi A, Faliva MA, Sala P, Perna S, et al. Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, placebo-controlled trial. International journal of food sciences and nutrition. 2013;64(1):7-15.

57.Brown JE, Rice-Evans CA. Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro. Free radical research. 1998;29(3):247-55.

58.Pérez-García F, Adzet T, Cañigueral S. Activity of artichoke leaf extract on reactive oxygen species in human leukocytes. Free radical research. 2000;33(5):661-5.

59.Panichi V, Migliori M, De Pietro S, Taccola D, Bianchi AM, Giovannini L, et al. C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure. Nephron. 2002;91(4):594-600.

60.Lacson E, Jr., Levin NW. C-reactive protein and end-stage renal disease. Semin Dial. 2004;17(6):438-48.

61.Deng J, Wu Q, Liao Y, Huo D, Yang Z. Effect of statins on chronic inflammation and nutrition status in renal dialysis patients: a systematic review and meta-analysis. Nephrology (Carlton, Vic). 2012;17(6):545-51.

62.Ben Salem M, Affes H, Ksouda K, Dhouibi R, Sahnoun Z, Hammami S, et al. Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits. Plant foods for human nutrition (Dordrecht, Netherlands). 2015;70(4):441-53.

63.Ben Salem M, Affes H, Athmouni K, Ksouda K, Dhouibi R, Sahnoun Z, et al. Chemicals Compositions, Antioxidant and Anti-Inflammatory Activity of Cynara scolymus Leaves Extracts, and Analysis of Major Bioactive Polyphenols by HPLC. Evidence-based complementary and alternative medicine : eCAM. 2017;2017:4951937.

64.Fabre J, Balant L. Renal failure, drug pharmacokinetics and drug action. Clinical pharmacokinetics. 1976;1(2):99-120.



منبع: معاونت پژوهشي دانشکده پزشکي