Zygophyllum album aqueous extract reduces oxidative damage in red blood cells and attenuates pro-inflammatory plasma markers in hypercholesterolemic-diabetic rats

Yasmina BAHLIL, Djamil KROUF, Nawal TALEB-DIDA

DOI: http://dx.doi.org/10.5138/09750185.2451


Zygophyllum album (Z. album) is used in traditional medicine for a long time for its anti-diabetic activities. This study had to assess Z. album extract supplementation effects on redox and inflammatory statuses in hypercholesterolemic-diabetic rats. Male rats Wistar (n=36), weighing 200±10 g were divided into three groups (n=12). The first group was rendered hypercholesterolemic (HC) with a high cholesterol diet (1 %). The second group was rendered diabetic (D) by intraperitoneal injection of streptozotocin (STZ) (35 mg/kg of body weight). The third group was rendered hypercholesterolemic-diabetic (HC-D); each group was divided into two groups (n=6), untreated groups (HC, D, HC-D) and treated groups with 1 % Z. album extract (HC-Za, D-Za and HC-D-Za). After 28 days, Z. album treatment lead to a decrease in RBC’s TBARS contents in HC-Za (-44 %), D-Za (-66 %) and HC-D-Za (-23 %) groups. An increase in the antioxidant enzymes activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) was observed in HC-Za, D-Za and HC-D-Za (p <0.05). IL-1 β and IL-6 concentrations were reduced by -44, -50 and -33 % and -49, 38 and -41 %, respectively in treated groups. A decrease in TNF-α as well as homocysteine and CRP was observed in Z. album treated groups (p <0,05). In conclusion, Z. album reduces radical attack and improves the anti-inflammatory proprieties in hypercholesterolemic-diabetic rats.


Hypercholesterolemia; Diabetes; Zygophyllum album; RBC; Oxidative stress; inflammation.


1. Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L and Giorgino F. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascular Pharmacology 2018; 100:1-19.

2. Hulsmans M and Holvoet P. The vicious circle between oxidative stress and inflammation in atherosclerosis. Journal of Cellular and Molecular Medicine 2010;14(1-2):70-78.

3. Münzel T, Camici GG, Maack C, Bonetti NR, Fuster V and Kovacic JC. Impact of Oxidative Stress on the Heart and Vasculature Part 2 of a 3-Part Series. Journal of the American College of Cardiology 2017; 70(2):212-229.

4. Keane KN, Cruzat VF, Carlessi R, de Bittencourt Jr PI and Newsholme P. Molecular events linking oxidative stress and inflammation to insulin resistance and b-cell dysfunction. Oxidative Medicine and Cellular Longevity 2015; 2015:15.

5. Bjørklund G and Chirumbolo S. Role of oxidative stress and antioxidants in daily nutrition and human health. Nutrition 2017; 33:311-321.

6. Li H, Horke S and Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis 2014; 237(1):208-219.

7. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H and Kim KY. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1- associated periodic syndrome (TRAPS). Journal of Experimental Medicine 2011; 208(3): 519-533.

8. Zhou R, Yazdi AS, Menu P and Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469(7329):221-225.

9. Patti ME and Corvera S. The role of mitochondria in the pathogenesis of type 2 diabetes. Endocrine Reviews2010; 31(3):364-395.

10. Wenzel P, Kossmann S, Münzel T and Daiber A. Redox regulation of cardiovascular inflammation-immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species. Free Radical Biology and Medicine 2017; 109: 48-60.

11. Chattopadhyay M, Khemka VK, Chatterjee G, Ganguly A, Mukhopadhyay S and Chakrabarti S. Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects. Molecular and Cellular Biochemistry 2015; 399 (1-2):95-103.

12. Kanikarla-Marie P and Jain SK. Role of Hyperketonemia in Inducing Oxidative Stress and Cellular Damage in Cultured Hepatocytes and Type 1 Diabetic Rat Liver. Cellular Physiology and Biochemistry 2015; 37(6):2160-2170.

13. He L, He T, Farrar S, Ji L, Liu T and Ma X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cellular Physiology and Biochemistry 2017; 44(2):532-553.

14. Marik PE. Chapter 76 - Endocrinology of the Stress Response During Critical Illness. In: Ronco, C., Bellomo, R., Kellum, J.A. and Ricci, Z., editors. Critical Care Nephrology 2019 (Third. Edition). Philadelphia: Content Repository Only!; . p. 446-54.e4.

15. Goldfine AB and Shoelson SE. Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk. Journal of Clinical Investigation 2017;127(1):83-93.

16. Saltiel AR and Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. Journal of Clinical Investigation 2017; 127(1):1-4.

17. Liese AD, Ma X, Ma X, Mittleman MA, The NS, Standiford DA, Lawrence JM, Pihoker C, Marcovina SM, Mayer-Davis EJ and Puett RC. Dietary Quality and Markers of Inflammation: No Association in Youth with Type 1 Diabetes in the Search for Diabetes in Youth Study. Journal of Diabetes and its Complications 2017; 32(6):179-184.

18. Colina-Coca C, González-Peña D, de Ancos B and Sánchez-Moreno C. Dietary onion ameliorates antioxidant defence, inflammatory response, and cardiovascular risk biomarkers in hypercholesterolemic Wistar rats. Journal of Functional Foods 2017; 36(7): 300-309.

19. Zanchet B, Gomes DB, Corralo VS, Diel KAP, Schönell AP, Faust C, Nicola P, Muller LG, Zanatta AP, Wildner SM, Bevilaqua F, Chitolina R, Sachett A and Zanatta L. Effects of hydroalcoholic extract of Celtis iguanaea on markers of cardiovascular diseases and glucose metabolism in cholesterol-fed rats. Revista Brasileira de Farmacognosia 2018; 28(1):80-91.

20. Chávez-Sánchez L, Espinosa-Luna JE, Chávez-Rueda K, Legorreta-Haquet MV, Montoya-Díaz E and Blanco-Favela F. Innate immune system cells inatherosclerosis. Archives of Medical Research 2014; 45:1-14.

21. World Health Organization (WHO). A report of the consultation meeting on traditional and modern medicine: Harmonizing two approaches. World Health Organization 2015, Beijing, Geneva, Suisse .

22. Bouasla A and Bouasla I. Ethnobotanical survey of medicinal plants in northeastern of Algeria. Phytomedicine 2017; 36:68-81.

23. Bading Taika B, Bouckandou M, Souza A, Bourobou Bourobou HP, MacKenzie LS and Lione L. An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology. Journal of Ethnopharmacology 2018; 216:203-228.

24. Azzi R, Djaziri R, Lahfa F, Sekkal FZ, Benmehdi H and Belkacem N. Ethnopharmacological survey of medicinal plants used in the traditional treatment of diabetes mellitus in the North Western and South Western Algeria. The Journal of Medicinal Plants Research 2012; 6(10):2041-2050.

25. Bedekar A, Shah K and Koffas M. Natural products for type II diab etes treatment”, Advances in applied microbiology 2010; 71:21-73.

26. Achi NK, Ohaeri OC, Ijeh II and Eleazu C. Modulation of the lipid profile and insulin levels of streptozotocin induced diabetic rats by ethanol extract of Cnidoscolus aconitifolius leaves and some fractions: Effect on the oral glucose tolerance of normoglycemic ras. Biomedicine & Pharmacotherapy 2017; 86:562-569.

27. El-Sayyad, H.I.H., Elmansi, A.A. and Bakr, E.H. Hypercholesterolemia induced ocular disorder: Ameliorating role of phytotherapy. Nutrition 2015; 31(5): 1307-1316.

28. Belmimoun A, Meddah B, Sid Elarbi K and Sonnet P. Phytochemical study of Zygophyllum album extract. International Journal of Engineering Management 2017; 4(5):1-10.

29. El Ghoul J and Ben-Attia M. Vasorelaxant Effects of Aqueous Extract of Zygophyllum Album and Antihyperglycemic Activities in Streptozotocin-Induced Diabetic Mice”, Journal of Diabetes & Metabolic Disorders 2014; 5(9): 426-432.

30. Bahlil Y, Krouf D and Taleb-Dida N. Zygophyllum album aqueous extract reduces glycemia and ameliorates lipid profile and oxidative damage in hypercholesterolemic-diabetic rats. Nutrition & Food Science 2019; 49(1):141-157.

31. Louhimies S. Directive 86/609/EEC on the Protection of Animals Used for Experimental and Other Scientific Purposes. Alternatives to Laboratory Animals. 2002; 30(suppl 2): 217-219.

32. Wang YM, Zhang B, Xue Y, Li ZJ, Wang JF, Xue CH and Yanagita T. The mechanism of dietary cholesterol effects on lipids metabolism in rats Lipids in Health and Diseases 2010; 9: 4-9.

33. Islam MS and Wilson RD. Experimentally induced rodent models of type 2 diabetes. Methods in Molecular Biology 2012; 933:161-174.

34. Zhang M, Lv X, Li J, Meng Z, Wang Q, Chang WG, Li W, Chen L and Liu Y. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis Molecular and cellular endocrinology 2012; 363(1-2):122-130.

35. Quintanilha AT, Packer L, Davies JM, Racanelli TL and Devies KJ. Membrane effects of vitamin E deficiency: bioenergetic and surface charge density studies of skeletal muscle and liver mitochondria. Annals of the New York Academy of Sciences 1982; 39:32-47.

36. Brown JM, Grosso MA, Terada LS, Beehler CJ, Toth KM, Whitman GJ, Harken AH and Repine JE. Erythrocytes decrease myocardial hydrogen peroxide levels and reperfusion injury. American Journal of Physiology 1989; 256:H584-H588.

37. Sedlak J and Lindsay RH. Estimation of total protein bound and non-protein sulfhydryl groups in tissues with Ellman's reagent. Analytical Biochemistry 1968; 25(1):192-205.

38. Schultz-Moreira AR, Olivero-David R, Vázquez-Velasco M, González-Torres L, Benedí J, Bastida S and Sánchez-Muniz FJ. Protective effects of sea spaghetti-enriched restructured pork against dietary cholesterol: effects on arylesterase and lipoprotein profile and composition of growing rats. Journal of Medicinal Food 2014; 17(8):921-928.

39. Lassoued I, Trigui M, Ghlissi Z, Nasri R, Jamoussi K, Kessis M, Sahnoun Z, Rebai T, Boualga A, Lamri-Senhadji M, Nasri M and Barkia A. Evaluation of hypocholesterolemic effect and antioxidant activity of Boops boops proteins in cholesterol-fed rats. Food & Function 2014; 5(6):1224-1231.

40. Zein S, Rachidi S and Hininger-Favier I. Fer, stress oxydant et diabète gestationnel. Médecine des Maladies Métaboliques 2013 ; 7(2) : 144-148.

41. Othman AI, El-Sawi MR, El-Missiry, MA and Abukhalil MH. Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats. Biomedicine & Pharmacotherapy 2017; 94:362-373.

42. Ezuruike UF and Prieto JM. Review: The Use of Plants in the Traditional Management of Diabetes in Nigeria: Pharmacological and Toxicological Considerations. Journal of Ethnopharmacology 2014;155: 857-924.

43. Okamoto T, Gohil K, Finkelstein EI, Bove P, Akaike T and Vander Vliet A. Multiple contributing roles for NOS2 in LPS-induced acute airway inflammation in mice. American Journal of Physiology-Lung Cellular and Molecular Physiology 2004; 286(1):L198-209.

44. Giustarini D, Colombo G, Garavaglia ML, Astori E, Portinaro NM, Reggiani F, Badalamenti S, Aloisi AM, Santucci A, Rossi R, Milzani A and Dalle-Donne I. Assessment of glutathione/glutathione disulphide ratio and S-glutathionylated proteins in human blood, solid tissues, and cultured cells. Free Radical Biology & Medicine 2017;112: 360-375.

45. Giustarini D, Galvagni F, Donne ID, Milzani A, Severi FM, Santucci A and Rossi R. N-acetylcysteine ethyl ester as GSH enhancer in human primary endothelial cells: a comparative study with other drugs. Free Radical Biology and Medicine 2018; 126:202-209.

46. Fournet M, Bonté F and Desmoulière A. Glycation Damage: A Possible Hub for Major Pathophysiological Disorders and Aging. Aging and Disease 2018; 9(5): 880-900.

47. Zidan Y, Bouderbala S and Bouchenak M. Portulaca oleracea aqueous extract reduces oxidative stress in erythrocytes and tissues, in rats fed enriched-cholesterol diet. Journal of Experimental and Integrative Medicine 2016; 6(1): 21-25.

48. Berzou S, Krouf D, Dida N, Taleb-Senouci D and Guenzet A. Effects of Zygophyllum gaetulum Aqueous Extract on Erythrocytes Lipid Peroxidation and Paraoxonase 1 Activity in Hypercholesterolemic Rats. International Journal of Pharmacognosy and Phytochemical Research 2016; 8(10):1689-1694.

49. Magnuson A, Fouts J, Booth A and Foster M. Obesity-induced chronic low-grade inflammation: Gastrointestinal and adipose tissue crosstalk. Integrative Obesity and Diabetes 2015; 1(5): 103-108.

50. Choi JJ, Park MY, Lee, HJ, Yoon, DY, Lim Y, Hyun JW, Zouboulis CC and Jin M. TNF-α increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes. The Journal of Dermatological Science 2012; 65(3): 179-188.

51. Ramírez-Alvarado MM and Sánchez-Roitz C. Tumor necrosis factor-α, insulin resistance, the lipoprotein metabolism and obesity in humans. Nutrición Hospitalaria 2012; 27(6): 1751-1757.

52. Yida Z, Imam MU, Ismail M, Ismail N, Ideris A and Abdullah MA. High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats. Journal of Biomedical Science J Biomed Sci 2015; 22(1): 96.

53. Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L and Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha”, Archives of Physiology and Biochemistry 2008; 114(3): 183-194.

54. Yadav R, Khan SH, Mada SB, Meena S, Kapila R and Kapila S. Consumption of Probiotic Lactobacillus fermentum MTCC:5898-Fermented Milk Attenuates Dyslipidemia, Oxidative Stress, and Inflammation in Male Rats Fed on Cholesterol-Enriched Diet. Probiotics and antimicrobial proteins 2018; 11(2):509-518.

55. Pirchl M, Ullrich C, Sperner-Unterweger B and Humpel C. Homocysteine has anti-inflammatory properties in a hypercholesterolemic rat model in vivo. Molecular and Cellular Neuroscience 2012; 49(4):456-463.

56. Feriani A, Hachani R, Kaabi B, Ncir M, El Feki A and Allagui MS. Protective effects of Zygophyllum album extract against deltamethrin-induced hyperglycemia and hepato-pancreatic disorders in rats. The Canadian Journal of Physiology and Pharmacology 2016;94(11): 1202-1210.

57. Kandouli C, Cassien M, Mercier A, Delehedde C, Ricquebourg E, Stocker P, Mekaouche M, Leulmi Z, Mechakra A, Thétiot-Laurent S, Culcasi M and Pietri S. Antidiabetic, antioxidant and anti-inflammatory properties of water and n-butanol soluble extracts from Saharian Anvillea radiata in high-fat-diet fed mice. Journal of Ethnopharmacology 2017; 207: 251-267.

58. Sreeja PS, Arunachalam K, de Oliveira Martins DT, da Silva Lima JC, Balogun SO, Pavan E, Saikumar S, Dhivya S, Kasipandi M and Parimelazhagan T. Sphenodesme involucrate var. paniculata (C.B. Clarke) Munir.: chemical characterization, anti-nociceptive and anti-inflammatory activities of methanol extract of leaves. Journal of Ethnopharmacology 2018; 225: 71-80.

59. Heyman L, Axling U, Blanco N, Sterner O, Holm C and Berger K. Evaluation of beneficial metabolic effects of berries in high-fat fed C57BL/6J mice. Journal of Nutrition and Metabolism 2014; 2014(3): 1-12.

60. Lee IS, Kim DY and Choi BY. Antioxidative activity of blueberry leaf extract prevents high-fat induced obesity in C57BL/6 mice. European Journal of Cancer Prevention 2014; 19(3):209-215.

61. Kim HP, Son KH, Chang HW and Kang SS. Anti-inflammatory Plant Flavonoids and Cellular Action Mechanisms. Journal of Pharmacological Sciences 2004; 96(3):229-245.

62. Choucry MA, Khalil MNA and El Awdan SA. Protective action of Crateva nurvala Buch. Ham extracts against renal ischaemia reperfusion injury in rats via antioxidant and anti-inflammatory activities. Journal of Ethnopharmacology 2018; 214: 47-57.


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