The Role of Christine A Saponins Molecules in the Control of Mild Chronic Inflammation in Obesity Related with Type-II Diabetes Mellitus

Document Type : Review Article

Authors

1 Department of Biomedical Engineering, Schoo of Engineering, University of Isfahan, Iran

2 Assistant Professor, Department of Biomedical Engineering, School of Engineering, University of Isfahan, Iran

Abstract

Obesity is always associated with chronic (low-grade) inflammation, which causes insulin-resistance in type-II diabetes mellitus. Dramatically, cholesterol level rises with starting diabetes and lower insulin level. With this increment, the statistical observations indicate a high risk of vascular diseases such as atherosclerosis. Therefore, the direct relationship between these complications, which is known to be the most important cause of mortality in these patients, has led scientists to take a serious and effective look at developing strategies and methods for controlling the inflammation of the immune system. Recent findings in the field of medicinal herbals and ingredients has shown that their macromolecules, due to specific structures and viability, have a potential impact on immune function of various aspects such as controlling inflammation, and modification or suppression of specific performance; using of those medicinal plants is emphasized by the World Health Organization, too. The global extensive studies about immunological effects of plant extracts such as Saponin molecules in cedar leaf extract have led to the discovery of compounds with amazing anti-inflammatory effects. Research conducted in Iran and elsewhere on plants containing active ingredient Saponins Christine A has shown that this group of plant molecules, as significant inhibitor of phosphorylation complex, with inhibition of inhibitor IĸBα nuclear factor kappa B (IĸBα-NF-ĸb), cause to modulate the induction of inducible nitric oxide synthase (iNOS) gene expression in the cytoplasm. Moreover, by disrupting the nitric oxide equilibrium in inflammatory environments, it can relieve mild tissue inflammation, which can improve obesity related to type-II diabetes mellitus and its complications. As an overall assessment of the reviewed studies, it can be concluded that the Saponins, especially molecules Saponins Christine A, can be considered seriously as a natural proimmuno-drug in treatment of inflammation of mild chronic obesity in type-II diabetes, and related complications such as insulin resistance, type-II diabetes, hypercholesterolemia, and arteriosclerosis.

Keywords

References

  1. Ghorbani M. A review of type 2 diabetes and obesity. New Cellular and Molecular Biotechnology Journal 2015; 5(18): 9-14. [In Persian].
  2. Khazaei M, Rouzbahani R. Obesity and inflammation: Role of adipokines. J Isfahan Med Sch 2016; 34(372): 148-56. [In Persian].
  3. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96(9): 939-49.
  4. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 2003; 14(6): 561-6.
  5. Matsuzawa Y. The metabolic syndrome and adipocytokines. FEBS Lett 2006; 580(12): 2917-21.
  6. Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010; 18(5): 884-9.
  7. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol 2010; 316(2): 129-39.
  8. Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008; 29(24): 2959-71.
  9. Tilg H, Moschen AR. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006; 6(10): 772-83.
  10. Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler 2013; 9(4): 247-53.
  11. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011; 11(2): 85-97.
  12. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013; 2013: 139239.
  13. Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells 2014; 37(5): 365-71.
  14. Akhtari Z, Zaringhalam J, Eidi A, HaeriRuhani S A, Manaheji H, Tekieh E. Relation cellular- molecular between serum IL10 levels and hyperalgesia variation in adjuvant- induced arthritis. Iran South Med J 2015; 17(6): 1176-87. [In Persian].
  15. Neels JG, Olefsky JM. Inflamed fat: What starts the fire? J Clin Invest 2006; 116(1): 33-5.
  16. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab 2005; 90(4): 2282-9.
  17. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117(1): 175-84.
  18. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454(7203): 428-35.
  19. Shoelson SE, Lee J, Yuan M. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 2003; 27 Suppl 3: S49-S52.
  20. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001; 293(5535): 1673-7.
  21. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259(5091): 87-91.
  22. Esposito K, Pontillo A, Di PC, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: A randomized trial. JAMA 2003; 289(14): 1799-804.
  23. Hosseini SE, Tavakoli F, Karami M. Medicinal plants in the treatment of diabetes mellitus. Clin Exc 2014; 2(2): 64-89. [In Persian].
  24. Zimmet P, Dowse G, Finch C, Serjeantson S, King H. The epidemiology and natural history of NIDDM--lessons from the South Pacific. Diabetes Metab Rev 1990; 6(2): 91-124.
  25. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 1995; 44(8): 863-70.
  26. Hashemi, N., Mirfeyzi, S., Sahebari, M., Rezaeeyazdi, Z. Adipokines: Resistin and systemic rheumatic diseases. Med J Mashad Univ Med Sci 2015; 58(8): 473-480. [In Persian].
  27. Dinarello CA. Historical insights into cytokines. Eur J Immunol 2007; 37(Suppl 1): S34-S45.
  28. Large V, Arner P. Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia. Diabetes Metab 1998; 24(5): 409-18.
  29. Ghorbani M, Himms-Hagen J. Treatment with CL 316,243, a beta 3-adrenoceptor agonist, reduces serum leptin in rats with diet- or aging-associated obesity, but not in Zucker rats with genetic (fa/fa) obesity. Int J Obes Relat Metab Disord 1998; 22(1): 63-5.
  30. Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 2003; 148(3): 293-300.
  31. Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes 1988; 37(8): 1020-4.
  32. Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 1997; 100(5): 1230-9.
  33. Cuzzocrea S, Mazzon E, Calabro G, Dugo L, De Sarro A, van De Loo FA, et al. Inducible nitric oxide synthase-knockout mice exhibit resistance to pleurisy and lung injury caused by carrageenan. Am J Respir Crit Care Med 2000; 162(5): 1859-66.
  34. Mirzaei F, Khazaei M. Role of nitric oxide in biological systems: A systematic review. J Mazandaran Univ Med Sci 2017; 27(150): 192-222. [In Persian].
  35. Connelly L, Jacobs AT, Palacios-Callender M, Moncada S, Hobbs AJ. Macrophage endothelial nitric-oxide synthase autoregulates cellular activation and pro-inflammatory protein expression. J Biol Chem 2003; 278(29): 26480-7.
  36. Bredt DS. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic Res 1999; 31(6): 577-96.
  37. Pellacani A, Wiesel P, Razavi S, Vasilj V, Feinberg MW, Chin MT, et al. Down-regulation of high mobility group-I(Y) protein contributes to the inhibition of nitric-oxide synthase 2 by transforming growth factor-beta1. J Biol Chem 2001; 276(2): 1653-9.
  38. Hosking H. Nitric oxide and the immune system: a literature review. The Plymouth Student Scientist 2009; 2(2): 270-8.
  39. Achike FI, Kwan CY. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway. Clin Exp Pharmacol Physiol 2003; 30(9): 605-15.
  40. Bogdan C, Rollinghoff M, Diefenbach A. The role of nitric oxide in innate immunity. Immunol Rev 2000; 173: 17-26.
  41. Schneemann M, Schoeden G. Macrophage biology and immunology: Man is not a mouse. J Leukoc Biol 2007; 81(3): 579.
  42. Ibiza S, Serrador JM. The role of nitric oxide in the regulation of adaptive immune responses. Inmunologia 2008; 27(3): 103-17.
  43. Connelly L, Palacios-Callender M, Ameixa C, Moncada S, Hobbs AJ. Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide. J Immunol 2001; 166(6): 3873-81.
  44. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol 2002; 2(10): 725-34.
  45. Sharifat N, Jafari-Hafshejani F, Dayati P, Lorestanpoor P, Paydar A, Babaahmadi Rezaei H. Inhibitory effect of Curcumin on phosphorylation NFκB-p65 induced by hydrogen peroxide in Bovine Endothelial Cells. J Fasa Univ Med Sci 2017; 7(2): 283-90. [In Persian].
  46. Tripathi P, Aggarwal A. NF-kB transcription factor: A key player in the generation of immune response. Curr Sci 2006; 90(4): 519-31.
  47. DangLi R, HeKong W, JiQin L, MingHua Z, WenCheng Z. ROS-induced ZNF580 expression: A key role for H2O2/NF-kappaB signaling pathway in vascular endothelial inflammation. Mol Cell Biochem 2012; 359(1-2): 183-91.
  48. Sintara K, Thong-Ngam D, Patumraj S, Klaikeaw N, Chatsuwan T. Curcumin suppresses gastric NF-kappaB activation and macromolecular leakage in Helicobacter pylori-infected rats. World J Gastroenterol 2010; 16(32): 4039-46.
  49. Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci 2004; 75(6): 639-53.
  50. Anggard E. Nitric oxide: mediator, murderer, and medicine. Lancet 1994; 343(8907): 1199-206.
  51. Musial A, Eissa NT. Inducible nitric-oxide synthase is regulated by the proteasome degradation pathway. J Biol Chem 2001; 276(26): 24268-73.
  52. Arner P. Not all fat is alike. Lancet 1998; 351(9112): 1301-2.
  53. Eaton SB, Konner M, Shostak M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med 1988; 84(4): 739-49.
  54. Abate N, Garg A. Heterogeneity in adipose tissue metabolism: Causes, implications and management of regional adiposity. Prog Lipid Res 1995; 34(1): 53-70.
  55. Ritenbaugh C, Goodby CS. Beyond the thrifty gene: metabolic implications of prehistoric migration into the New World. Med Anthropol 1989; 11(3): 227-36.
  56. Packard CJ. The case for cholesterol: Lowering LDL-C for cardiovascular disease. Proceedings of the 85th European Atherosclerosis Society Annual Congress (EAS 2017); 2017 Apr 23-26; Prague, Czech Republic.
  57. Libby P. The case for immune cells: an expanded cardiovascular continuum. Proceedings of the 85th European Atherosclerosis Society Annual Congress (EAS 2017); 2017 Apr 23-26; Prague, Czech Republic.
  58. Zakynthinos E, Pappa N. Inflammatory biomarkers in coronary artery disease. J Cardiol 2009; 53(3): 317-33.
  59. Vakili T, Eftekhar E, Nourooz Zadeh J, Khademvatan K, Salary Lak S. Inter-relationships between inflammatory biomarkers and severity of angiographically verified coronary artery occlusion. J Birjand Univ Med Sci 2013; 20(3): 288-94. [In Persian].
  60. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340(2): 115-26.
  61. Koenig W, Khuseyinova N, Baumert J, Thorand B, Loewel H, Chambless L, et al. Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Arterioscler Thromb Vasc Biol 2006; 26(12): 2745-51.
  62. Gigante B, Bennet AM, Leander K, Vikstrom M, de FU. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men. PLoS One 2010; 5(6): e11300.
  63. Back M, Yurdagul A, Jr., Tabas I, Oorni K, Kovanen PT. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol 2019; 16(7): 389-406.
  64. Zernecke A. Dendritic cells in atherosclerosis: evidence in mice and humans. Arterioscler Thromb Vasc Biol 2015; 35(4): 763-70.
  65. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol 2009; 27: 165-97.
  66. Hansson GK, Libby P, Tabas I. Inflammation and plaque vulnerability. J Intern Med 2015; 278(5): 483-93.
  67. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105(9): 1135-43.
  68. Eslami F, Sarafbidabad M, Mirahmadi-Zare SZ, Kiani-esfahani A. A new immunomodulatory drug delivery system based on αlβ2 and αmβ2 aptamers/Alg-PEI. International Pharmacy Acta 2018; 1(1): 14.
  69. Eslami F, Sarafbidabad M. Biocompatibility enhancement of tissue engineering scaffold with immuno-modulation by simulated dendritic cell surfasces markers molecules [MSc Thesis]. Isfahan, Iran: Faculty of engineering, Department of Biomedical Enginnering, University of Isfahan; 2017. [In Persian].Ref Type: Generic
  70. Afshar M, Sattari Fard H, Shadi M, Ghaderi R. Repairing effects of Iran flora on wound healing. J Birjand Univ Med Sci 2015; 22(1): 1-18. [In Persian].
  71. Asadbegy M, Mirazi N, Vatanchian M. Comparative study of lotus corniculatus l. hydroethanolic extract and phenytoin ointment effects on rat skin wound healing: morphometrical and histopathological Studies. Journal of Cell and Tissue 2011; 2(3): 213-23. [In Persian].
  72. Lacaille-Dubois MA. Bioactive saponins with cancer related and immunomodulatory activity: Recent developments. Studies in Natural Products Chemistry 2005; 32: 209-46.
  73. Sarafbidabad M, Nazemoroaya Z. Synthesis of nanophytosome based on saponins. Proceedings of the 24th Iranian Seminar of Organic Chemistry; 2016 Aug 24-26; Tabriz, Iran. [In Persian].
  74. Nazemoroaya Z, Sarafbidabad M. Preparation and characterization of saponin-enriched extract of Zizyphus spina- christi and design of a novel saponin-phospholipid complex as an effective drug delivery tool. International Pharmacy Acta 2018; 1(1): 124.
  75. Tavakoli S, Hajiaghaei R, Hajiakhoondi A. Comprehensive textbook of Pharmacognosy. Tehran, Iran: Etminan Publications; 2017. [In Persian].
  76. Samsam-Shariat H, Moatar F. Natural herbs (Materia Medica). Isfahan, Iran: Mashal Publicatins; 1986. [In Persian].
  77. Nazemoroaya Z, Sarafbidabad M. Synthesis of nanophytosome based on zizyphus genus (Zizyphus spina christi) by nanoemultion technique [MSc Thesis]. Isfahan, Iran: Faculty of Engineering, Department of Biomedical Engineering, University of Isfahan; 2017. [In Persian].
  78. Ghasemi Dehkordi N. Iranian herbal pharmacopoeia. Tehran, Iran: Iranian Ministry of Health and Medical Education; 2002. [In Persian].
  79. Asgarpanah J, Haghighat E. Phytochemistry and pharmacologic properties of Ziziphus spina christi (L.) Willd. Afr J Pharm Pharmacol 2012; 6(31): 2332-9.
  80. Michel CG, Nesseem DI, Ismail MF. Anti-diabetic activity and stability study of the formulated leaf extract of Zizyphus spina-christi (L.) Willd with the influence of seasonal variation. J Ethnopharmacol 2011; 133(1): 53-62.
  81. Moinifard M, Hedayati M. Alloxan and streptozotocin, tools for diabetes research. Journal of Applied Exercise Physiology 2015; 10(20): 13-22. [In Persian].
  82. Abdel-Zaher AO, Salim SY, Assaf MH, Abdel-Hady RH. Antidiabetic activity and toxicity of Zizyphus spina-christi leaves. J Ethnopharmacol 2005; 101(1-3): 129-38.
  83. Yang CY, Wang J, Zhao Y, Shen L, Jiang X, Xie ZG, et al. Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components. J Ethnopharmacol 2010; 130(2): 231-6.
  84. Gepdiremen A, Mshvildadze V, Suleyman H, Elias R. Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema. Phytomedicine 2005; 12(6-7): 440-4.
  85. Sarafbidabad M. No-Immunosuponinosome engineering for melanoma cancer cells treatment and growth control. Aplication of Biotechnology in Medical Science; Isfahan, Iran: Royan Institute for Biotechnology; 2018. [In Persian].
  86. Zhao Y, Sun X, Yu X, Gao R, Yin L. Saponins from Panax notoginseng leaves improve the symptoms of aplastic anemia and aberrant immunity in mice. Biomed Pharmacother 2018; 102: 959-65.
  87. Naroyie S, Khani V, Edris Arbab M, Molla Shahi M. A comprehensive pharmacological reference for generic drugs in Iran. Tehran, Iran: Abnous Publications; 2010. [In Persian].
  88. Khanizadeh A, Karimzadeh F. Experimental models of rheumatoid arthritis: Acute and chronic pain. Shefaye Khatam 2017; 5(1): 98-109. [In Persian].
  89. Gupta A, Chaphalkar S. Immunosuppressive activity of crude saponins from the leaves of Calotropis gigantea, Calamus roteng and Artocarpus integrifolia. Int J Pharm Sci Res 2015; 6(3): 526-31.
Journal of Isfahan Medical School
Volume 38, Issue 564 - Serial Number 564
January and February 2020
Pages 85-98

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History

  • Receive Date: 25 September 2019
  • Revise Date: 02 November 2024
  • Accept Date: 06 April 2022

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