Antidiabetic and Immunomodulatory Effects of Oleuropein and Vitamin C in Diabetic Male Rats

  • Nema Abdelhameed Mohamed Alexandria University, Egypt
  • Heba Mohamed Abdou Alexandria University, Egypt
  • Marium Mohamed Marzouk Omar El-Mokhtar University, Libya
Keywords: Oleuropein, Vitamin C, Diabetes, Oxidative Stress, Immunity, Male Rats

Abstract

The present work was designed to study the antidiabetic and immunomodulatory effects of olive leaf polyphenol (Oleuropein) and vitamin C in diabetic male rats. Diabetes was induced by a single i.p. dose of STZ (40 mg/kg b.w.). Pure oleuropein compound (5 mg/kg b.w.) and vit. C (150 mg/kg b.w.) were orally administered once per a day for 15 days after diabetes induction. Oleuropein and vitamin C showed a significant role in attenuating the blood glucose, insulin, pancreatic amylase, and hexokinase alterations and caused an elevation of antioxidant enzymes in diabetic rats. Oleuropein and vitamin C showed a hematopoetic action as documented by the increase in RBC, Hb, Hct, PLt, decrease in WBC and improved RBC structure. Oleuropein and vitamin C significantly attenuated the oxidative status of diabetic rats. Oleuropein and vitamin C improved the different changes in some cytokines and interlukines and decreases the gene expression of TNF-ALFA1.png, COX2, and caspase3 involved in apoptosis and inflammation. The immunohistochemical sections of pancreas in the diabetic rats treated with oleuropein and vitamin C showed a high intensity of insulin in BETA1.png-cells. Oleuropein as a natural active compound has antioxidant activity more or less like vitamin C to attenuate the effect of STZ-induced diabetes.

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Author Biographies

Nema Abdelhameed Mohamed, Alexandria University, Egypt

Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt

Heba Mohamed Abdou, Alexandria University, Egypt

Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt

Marium Mohamed Marzouk, Omar El-Mokhtar University, Libya

Department of Zoology, Faculty of Science, Omar El-Mokhtar University, Libya

References

He, L., He, T., Farrar, S., Ji, L., Liu, T. and Ma, X. (2017). Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem, 44, 532-553.

Esser, N., Paquot, N. and Scheen, AJ. (2015). Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert. Opini. Investig. Drugs, 24, 283-307.

Perakakis, N. and Mantzoros, CS. (2016). Immune therapy in type 1 diabetes mellitus- attempts to untie the Gordian knot? J. Metabolism, 65, 1278-1285.

Khan, MI. (2015). Stabilization of betalains: a review. Food Chem, 197, 1280-5.

Ramith, R., Prithvi, SS., Farhan, Z., Lakshmi, VR. and Nagendra, MNP. (2014). Inhibitory effect of banana (Musa sp. var. Nanjangud rasa bale) flower extract and its constituents Umbelliferone and Lupeol on a-glucosidase, aldose reductase and glycation at multiple stages. Afr. J. Bot, 95, 54-63.

Moudgil, D. and Khalil, A. (2016). The 1st Euro- Mediterranean Workshop: Natural Products in Health and Diseases. Asian. J. Pharm. Sci, 11, 292-296.

Kuem, N., Song, SJ., Yu, R., Yun, J., W., Park, T. (2014). Oleuropein attenuates visceral adiposity in high-fat diet-induced obese mice through the modulation of WNT10b- and galanin-mediated signalings. Mol. Nutr. Food. Res, 58, 2166-2176.

Barbaro, B., Toietta, G., Maggio, R., Arciello, M. et al. (2014). Effects of the olive derived polyphenol oleuropin on human health. Int. J. Mol. Sci, 15, 18508-18524.

Al-Azzawie, HF. and Alhamdani, MSS. (2006). Hypoglycemic and antioxidant effects of oleuropein in alloxan-diabetic rabbits. Life Sci, 78, 1371-1377.

Andreadou, I., Sigala, F., Iliodromitis, EK. et al. (2007). Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of xidative and nitrosative stress. J. Mol. Cell. Cardiol, 42, 549-558.

Combs, J. and Gerald, F. (2012). The Vitamins. 4 ed. Burlington: Elsevier Science. Ind. J. Pharm, 4, 211- 219.

Odum, EP., Ejilemele, AA. and Wakwe, VC. (2012). Antioxidant status of type 2 diabetic patients in Port Harcourt, Nigeria. Niger. J. Clin. Pract, 15, 55-58.

Mohamed, TA., Abouel-Nour, MF., Eldemerdash, R. and Ibrahim Elgalady, DAI. (2016). Therapeutic Effects of Bone Marrow Stem Cells in Diabetic Rats. J. Comput. Sci. Syst. Bio, l9, 058-068.

Sibghatullah, MA., Sangi, MI., Sulaiman, MF., Abd El-wahab, EIA. and Soad, SA. (2015). Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals. Pharmacogn. Mag, 11, 251-257.

Naziroglu, M. (2003). Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats. Protective role of vitamins C and E and selenium. Biol. Trace. Elem. Res, 94, 61-71.

Alimohammadi, S., Hobbenaghi, R., Javanbakht, J., Kheradmand, D. et al. (2013). Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: An experimental study with histopathological evaluation. Diagn. Pathol, 8-137.

Braham, D. and Trinder, P. (1972). Analyst, Methods for determination of blood glucose level by spectrophotometer. Anslyst, 97, 142-5.

Nathan, DM., Singer, DE., Hurxthal, K. et al. (1984). The clinical information value of the glycosylated hemoglobin assay. N. Engl. J. Med, 310, 341-346.

Finlay, JWA. and Dillard, RF. (2007). Appropriate Calibration Curve Fitting in Ligand Binding Assays. J. AAPS, 9, 260-267.

Pulse, S. (1972). Determination of amylase activity in vitro. Methods Enzymol. Jouyban 2 Spectrofluorimetric, 97-101.

Gubern, G., Canalias, F. and Gella, FJ. (1995). Determination of alpha-amylase activity, methods comparison and commutability study of several control materials. Clin. Chem. Mar, 41, 435-8.

Tappel, AL. and Zalkin, H. (1959). Lipid peroxidation in isolated mitochondria. Arch. Biochem. Biophys, 80, 326-332.

Richardson, M. and Mwephy, H. (1975). Effect of GSH depletionon tissue deposition of methyl mercury in rats. Toxicol. Appl. Pharmacol, 31, 505-519.

Marklund, S. and Marklund, G. (1974). Involvement of the superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem, 47, 469-474.

Aebi, H., Bergmeyer, HU., Gawehn, K., Williamson, DH. and Lund, P. (1974). Catalase (2nd ed.). In "Method of Enzymatic Analysis", (Eds.). Academic Press. Inc. New. York. London, 673-684.

Habig, WH., Pabst, MJ. and Jakoby, WB. (1974). Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem, 249, 7130-7139.

Paglia, DE. and Valentine, WN. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Transl. Res, 70, 158-169.

Chan and Perlstein. (1987). Immunoassay: A Practical Guide, Eds. Academic Press: New York, 71.

Ansar AS., Gogal, RM. and Walsh, JE. (1994). J. Immunol. Methods, 170, 211-224.

Ferguson-Smith, AC., Chen, YF., Newman, MS., May, LT. and Ruddle, FH. (1988). Regional localization of the interferon beta-2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome. Genomics, 2, 203-208.

Aboulker, JP., Autran, B., Bedjord, K., Touraine, F., Debre, P. (1992). Consistency of routine measurements of CD4þ, CD8þ peripheral blood lympocytes. J. Immunol. Methods, 154, 155-161.

Chomczynski, P. and Sacchi, N. (1987). "Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction". Anal. Biochem, 162, 156-159.

Livak, KJ. and Schmittgen, TD. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T) method. Methods, 25, 402-408.

Zaky, A., Mohammad, B., Moftah, M., Kandeel, KM., Bassiouny, AR. (2013). Apurinic/apyrimidinic endonuclease 1 is a key modulator of aluminum-induced neuroinflammation. BMC. Neurosci, 14-26.

Chiu, CJ., Chiang, CP., Chang, ML. et al. (2001). Association between genetic polymorphism of tumor necrosis factoralpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer. J. Dent. Res, 80, 2055-9.

Moustafa, AM. and Boshra, V. (2011). The possible role of Lcarnitine on the skeletal muscle of ovariectomized rats., J. Mol. Histol, 42, 217-225.

Hsu, SM., Raine, L. and Fanger, H. (1981). Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J. Histochem. Cytochem, 29, 577-580.

Busineni, JG. Dwarakanath, V. and Chikka, BK. (2015). Streptozotocin-A Diabetogenic Agent in Animal Models. Ijppr. Human, 3, 253-269.

Yang, DK. and Kang, HS. (2018). Anti-diabetic effect of cotreatment with quercetin and resveratrol in streptozotocin-induced diabetic rats. Biomol Ther, 26, 130-138.

Mohamed, NA. and Abdou, HM. (2015). The hypoglycemic and antioxidative effects of Centella asiatica against STZ-induced diabetic disorders in rats. Int. J. Pharm. Bio. Sci, 6, 621-633.

Mufeed, JE., Thana, MJ., Zinah, AA. and Muna, ME. (2014). Evaluation of amylase activity in patients with type 2 daibetes mellitus. Am. J. BioSci, 2, 171-174.

Selvaraja, W., William, N. and Dyeabura, A. (2011). Antidiabetic activity of crude stem extracts of coscinium fenestratum on streptozotocin-induced type-2 diabetic rats. A. J. Pharma. Clin. Res, 4, 47-51.

Yamamoto, N., Ueda-Wakagi, M., Sato, T. and Kawasaki, K. (2015). Measurement of Glucose Uptake in Cultured Cells. Curr. Protoc. Pharmacol, 14, 1-22.

Fujiwara, Y., Tsukahara, C., Ikeda, N., Sone, Y. Ishikawa, T. et al. (2017). Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4. J Clin Biochem Nutr., 61(3), 196-202.

Karabag-Coban, F., Omer, H., Mehmet, FB. and Sinan, I. (2017). Antioxidant Status and Anti-inflammatory Effects of Oleuropein in Streptozotocin-induced Diabetic Nephropathy in Rats. Eur. J. Med. Chem, 18, 1-10.

Carnevale, R., Silvestri, R., Loffredo, L. and Novo, M. (2018). Oleuropein, a component of extra virgin olive oil, lowers postprandial glycaemia in healthy subjects. Br. J. Clin. Pharmacol, 84, 1566-1574.

Aluwong, T., Ayo, J., O., Kpukple, A. and Oladipo, OO. (2016). Amelioration of Hyperglycaemia, Oxidative Stress and Dyslipidaemia in Alloxan-Induced Diabetic Wistar Rats Treated with Probiotic and Vitamin C. Nutrients, 8, 151-153.

Zhou, C., Lixin, N., Ruiqi SY., Cheng, Y., Li, X. and Changhao, S. (2016). Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators. PLoS. One, 11, 163-571.

Ashor, AW., Werner, AD., Lara, J., Willis, ND., Mathers, JC. and Siervo, M. (2017). Effects of vitamin C supplementation on glycaemic control: A systematic review and meta-analysis of randomised controlled trials. Eur. J. Clin. Nutr, 71, 1371-1380.

Ajiboye, BO., Oluwafemi AOj. and Oluwafemi, O. (2018). Ameliorative Activity of Ethanolic Extract of Artocarpus heterophyllus Stem Bark on Alloxan-induced Diabetic Rats. Adv Pharm Bull. 8, 141–147.

Khalafallah, A., Phuah, E., Al-Barazan, AM. et al. (2016). Glycosylated haemoglobin for screening and diagnosis of gestational diabetes mellitus. BMJ Open, 6, 11-59.

Karabag–coban, F., Ince, S., Kucukkurt, I., Demirel, HH. and Hazman, Ö. (2015). Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug. Chem. Toxicol, 38, 391-9.

Vitak, TY., Wasser, SP., Nevo, E. and Sybirna, NO. (2015). The Effect of the Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum (Higher Basidiomycetes) on the Erythron System in Normal and Streptozotocin-Induced Diabetic Rats. J. Int. Med, 17, 277-286.

Muller YD., Golshayan, D., Ehirchiou, D., Wyss, JC., Giovannoni, L. et al. (2011). Seebach Immunosuppressive Effects of Streptozotocin-Induced Diabetes Result in Absolute Lymphopenia and a Relative Increase of T Regulatory Cells. Diabetes, 60, 2331–2340.

Palanisamy, V. and Mariamichael, A. (2017). Diagnosis of Diabetes Mellitus by Extraction of Morphological Features of Red Blood Cells Using an Artificial Neural Network. Exp Clin Endocrinol Diabetes., 24(9), 548-556.

Neamtu, MC., CrsiToiu, S., Avramescu, ET. and Margina, DM. (2015). The prevalence of the red cell morphology changes in patients with type 2 diabetes mellitus. Rom J Morphol Embryol., 56(1), 183-9.

Zhang, M., Li, Xin. and Feng, J. (2012). Acute hypoxic ischemic mice blood viscosity and erythrocyte rheology change. Chin J Appl Physiol, 12, 454–457.

Fabiani, R., Rosignoli, P., De Bartolomeo, A., Fuccelli, R. et al. (2008). Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J. Nutr, 138, 1411-1416.

Geyikoglu, FG., Colak, S., Turkez, H. and Bakir, M. (2016). Oleuropein Ameliorates Cisplatin-induced Hematological Damages Via Restraining Oxidative Stress and DNA Injury. Indian. J. Hematol, 33, 348-354.

Matsui, T. (2012). Vitamin C nutrition in cattle. Asian-Australasian. J. Anim. Sci, 25, 597-605.

National Research Council (NRC), 2011. Nutrient requirements of fish and shrimp. Washington, DC, USA: National Academies Press, 207-209.

Lamas, GA., Boineau, R., Goertz, C., Mark, DB. et al. (2013). Oral High-Dose Multivitamins and Minerals or Post Myocardial Infarction Patients in TACT. Ann. Intern. Med, 159, 797-805.

Carr, AC. and McCall, C. (2017). The role of vitamin C in the treatment of pain: New insights. J. Transl. Med, 15, 77.

Bertran, EA., Berlie, HD., Taylor, A. et al. (2017). Diagnostic performance of HbA1c for diabetes in Arab vs. European populations: a systematic review and meta-analysis. Diabet Med, 34, 156-66.

Xiao, JB. and Högger, P. (2015). Dietary polyphenols and type 2 diabetes: current insights and future perspectives. Curr Med Chem, 22, 23–38.

Kotb, A. and Al Azzam, KMM. (2015). Effect of Vitamin C on Blood Glucose and Glycosylated Hemoglobin in Type II Diabetes Mellitus. Int J Anal Chem, 3, 6-8.

Sagoo, MK. and Gnudi, L. (2018). Diabetic nephropathy: Is there a role for oxidative stress? Free Radic. Biol. Med, 116, 50-63.

El-Beltagi, HS., Abdel-Mobdy, YE. and Abdel-Rahim, E. (2017). Toxicological influences of cyfluthrin attenuated by Solenostemma argel extracts on carbohydrate metabolism of male albino rats. Fresen. Environ. Bull, 26, 1673-1681.

Ngaski, AA. (2018). Correlation of antioxidants enzymes activity with fasting blood glucose in diabetic patients in Sokoto, Nigeria. Br. J. Med. Med. Res, 25, 1-6.

Abo Ghanema, I. and Sadek, KM. (2012). Olive Leaves Extract Restored the antioxidantPerturbations in Red Blood Cells Hemolysate in Streptozotocin nduced Diabetic Rats. International Journal of Medical and Biological Sciences, 6 (1), 181-187.

Salah, MB., Hafedh, A. and Manef, A. (2017). Anti-diabetic activity and oxidative stress improvement of Tunisian Gerboui olive leaves extract on alloxan induced diabetic rats. J. Mater, 8, 1359-1364.

Franke, SIR., Muller, LL., Santos, MC., Fishborn, A. et al. (2013). Vitamin C intake reduces the cytotoxicity associated with hyperglycaemia in prediabetes and type 2 diabetes. Biomed. Res. Int, 10, 11-55.

Hazman, ÖS. and Bozkurt, F. (2015). The antioxidant effect of boron on oxidative stress and DNA damage in diabetic rats. JFEB, 24, 11.

Kaufmann, FN. et al. (2017). NLRP3 inflammasome-driven pathways in depression: clinical and preclinical findings. Brain. Behav. Immun, 64, 367-383.

Moganti, K, Li., F., Schmuttermaier, C., Riemann, S., Kluter, H. et al. (2017). Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages. Immunobiology, 222, 952-959.

Furukawa, Y., Tamura, Y., Takeno, K., Funayama, T. et al. (2017). Impaired peripheral insulin sensitivity in nonobese Japanese with type 2 diabetes mellitus and fatty liver. J. Diabetes Investig, 10, 1111-12731.

Impellizzeri, D., Esposito, E., Mazzon, E., Paterniti, I., di Paola, R. et al. (2011). The effects of oleuropein aglycone, an olive oil compound, in a mouse model of carrageenan-induced pleurisy. Clin. Nutr, 30, 533-540.

Sánchez-Fidalgo, S., Cárdeno, A., Sánchez-Hidalgo, M., Aparicio-Soto, M., et al. (2013). Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice. J. Nutr. Biochem, 24, 1401-1413.

Larussa, T., Manuela, O., Evelina, S., Marta, G., Roberta, P. et al. (2017). Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients. Nutrients, 9, 391.

Di Paolo, N.C. and Shayakhmetov, DM. (2016). Interleukin 1a and the inflammatory process. Nat. Immunol, 17, 906-913.

Gao, YL., Lu, B., Zhai, JH., Liu, YC. et al. (2017). The parenteral vitamin C improves sepsis and sepsis-induced multiple organ dysfunction syndrome via preventing cellular immunosuppression. Mediat. Inflamm, 40, 246-72.

Qadir, N., Mustafa, K., Anwar, A., Suhailah, W. et al. (2016). Antidiabetic Effect of Oleuropein from Olea europaea Leaf against alloxan Induced Type 1 Diabetic in Rats Braz. arch. biol. technol. vol.59 Curitiba.

Lapidot, T., Walker, MD. and Kanner J. (2002). Antioxidant and prooxidant effects of phenolics on pancreatic B-cells in vitro. Journal of Agricultural and Food Chemistry, 50(25), 7220-5.

Wang, SC., Yang, N., Zhang, et al. (2014). “Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice,” PloS One, vol. 9, article e101315.

Zhou, C., Lixin, Na., Ruiqi S. and Yu, C. (2016). Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators PLoS One, 11(9), e0163571.

Published
2018-10-04
How to Cite
Mohamed, N. A., Abdou, H. M., & Marzouk, M. M. (2018). Antidiabetic and Immunomodulatory Effects of Oleuropein and Vitamin C in Diabetic Male Rats. JOURNAL OF ADVANCES IN BIOLOGY, 11, 2250-2268. https://doi.org/10.24297/jab.v11i0.7689

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