• FAROUK K EL-BAZ Department of Plant Biochemistry, National Research Centre, Giza, Egypt.
  • Hanan F Aly Department of Therapeutic Chemistry, National Research Centre, Giza, Egypt



Haematococcus pluvialis, Streptozotocin, Type 2 diabetes, Asymmetric dimethylarginine, Von Willebrand factor, Lipoxygenases, Histopathological examination


Objective: The purpose of the current study is to evaluate the antidiabetic influence of Haematococcus pluvialis (H. pluvialis) ethanolic extract on streptozotocin (STZ)-induced rats.

Methods: This influence was assessed by measuring; asymmetric dimethylarginine (ADMA), von willebrand factor (vWf), 15-lipoxygenase (15-LOX), 5-lipoxygenase (5-LOX), epidermal growth factor (EGF) and lipoxin-A4 (LXA4). The histopathological examinations of cardiac and renal tissues were also performed.

Results: The presented  results showed an elevation in the levels of ADMA, vWf, 15-LOXand 5-LOX with percentage increase  430.30, 77.54, 61.05 and 81.09 %, respectively in diabetic rats. However, the EGF and LXA4 levels were decreased significantly (44.17 and51.94%, respectively) compared to normal control rats. On the other hand, treatment of diabetic rats with H. pluvialis improved ADMA, vWf, 15-LOX, 5LOX, EGF and LXA4 levels with amelioration percentages; 269.69, 54.77, 55.78, 72.68, 53.39 and 56.58%, respectively. Additionally, the histopathological examination of diabetic cardiac tissue revealed congestion of myocardial blood vessel, vacuolation of the sarcoplasm of cardiac myocytes and focal necrosis of myocytes associated with inflammatory cells infiltration. Beside, vacuolation of epithelial lining of renal tubules and endothelial lining glomerular tuft as well as cystic dilatation of renal tubules were detected. However, cardiac tissue  and renal tubules of diabetic rats treated with H. pluvialis ethanolic extract (150 mg/kg b.wt.) showed normal cardiac myocytes, vacuolation of epithelial lining renal tubules and endothelial lining glomerular tuft, congestion of glomerular tuft and intertubular renal blood vessels.

Conclusion: These results confirmed the improving role of H. pluvialis in controlling type 2diabetes.



Download data is not yet available.

Author Biography

FAROUK K EL-BAZ, Department of Plant Biochemistry, National Research Centre, Giza, Egypt.

Plant Biochemistry


Malini P, Kanchana G, Rajadurai M. Antibiabetic efficacy of ellagic acid in streptozotocin induced diabetes mellitus in albino wistar rats. Asian J Pharm Clin Res 2011; 4:124-8.

Krzyzanowska K, Mittermayer F, Michael Wolzt, Schernthaner G. ADMA, cardiovascular disease and diabetes. Diabetes Res Clin Pract 2008;S122-S6.

Ueda S, Yamagishi S, Matsumoto Y, Fukami K, Okuda S. Asymmetric dimethyl arginine (ADMA) is a novel emerging risk factor for cardiovascular disease and the development of renal injury in chronic kidney disease. Clin Exp Nephrol 2007;11:115-21.

Abbasi F, Asagmi T, Cooke JP, Lamendola C, McLaughlin T, Reaven GM, Stuehlinger M, Tsao PS. Plasma concentrations of asymmetric dimethyl arginineare increased in patients with type 2 diabetes mellitus. Am J Cardiol 2001;88:1201-3.

Al-Ankily MM, Shamel M, Bakr MM. Epidermal growth factor and diabetes mellitus; friends or faux?. Int J Med Dent Sci 2016; 5:1290-6.

Wei F, Lin CC, Joon A, Feng Z, Troche G, Lira ME. Non-invasive saliva -based EGFR gene mutation detection in patients with lung cancer. Am J Respir Crit Care Med 2014; 190 :11117-26.

Serhan CN. Systems approach to inflammation resolution: identification of novelanti-inflammatory and pro-resolving mediators. J Thromb Haemost 2009;7:44-8.

Rai G, Joshi N, Jung JE, Liu Y, Schultz L,Yasgar A, Perry S, Diaz G, Zhang Q, Kenyon V, Jadhav A, Simeonov A, Lo EH, Leyen K, Maloney DJ, Holman TR. Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti-stroke therapies. J Med Chem 2014;57:4035-48.

Frankel DS, Meigs JB, Massaro JM, Wilson PWF, O’Donnell CJ, D’Agostino RB, Tofler GH. Von willebrand factor, type 2 diabetes and risk of cardiovascular disease: The Framingham Offspring Study. Circulation. 2009;118:2533-9.

Lee S, Jeon Y. Anti-diabetic effects of brown algae derived phlorotannins, marine polyphenols through diverse mechanisms. Fitoterapia 2013; 86:129-36.

Gammone MA, Riccioni G, D’Orazio N. Marine carotenoids against oxidative stress: effects on human health. Mar Drugs 2015;13:6226-46.

Yuan JP, Peng J, Yin K, Wang JH. Potential health-promoting effects of astaxanthin: A high-value carotenoid mostly from microalgae. Mol Nutr Food Res 2011;55:150-65.

Boussiba S. Carotenogenesis in the green alga Haematococcus pluvialis: Cellular physiology and stress response. Physiol Plantarum 2000;108:111-7.

Lorenz RT, Cysewski GR. Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. Tibtechnology 2000; 18:160-7.

Ursoniu S, Sahebkar A, Serban MC, Banach M. Lipid profile and glucose changes after supplementation with astaxanthin: A systematic review and meta-analysis of randomized controlled trials. Arch Med Sci 2015; 11:253-66.

Yang Y, Kim B, Lee JY. Astaxanthin structure, metabolism, and health benefits. J Hum Nutr Food Sci 2013; 1:1-11.

Stanier RY, Kunisawa MM, Cohn- Bazire G. Purification and properties of unicellular blue green algae (order chroococcales). Bacteriol Rev1971;35:171-201.

Olaizola M. Commercial production of astaxanthin from Haematococcus pluvialis using 25,000-liter outdoor photobioreactors. J Appl Phycol 2000; 12:499-506.

Liang H, Ma A, Zhang P, Bi SL, Shi DY. Effect of ethanol extract of alga Laurencia supplementation on DNA oxidation and alkylation damage in mice. Asia Pac J Clin Nutr 2007;16:164-8.

Milani E, Nikfar, S, Khorasani R, Zamani MJ, Abdollahi M. Reduction of diabetes-induced oxidative stress by phosphodiestrase inhibitors in rats. Comp Biochem Physiol Part C: Toxicol Pharmacol 2005; 140:251-5.

Rajesh V, Perumal P, Sundarrajan T. Antidiabetic activity of methanolic extract of Smilax zeylanica Linn in streptozotocin induced diabetic rats. Internet J Endocrinol 2009;6:1-5.

Shalaby NMM, Abd-Alla HI, Aly HF, Albalawy MA, Shaker KH, Bouajila J. Preliminary in vitro and in vivo evaluation of antidiabetic activity of Ducrosia anethifolia Boiss. and its linear furanocoumarins. BioMed Res Int 2014;1-13.

Dachicourt N, Bailb D, Gangnerou MN, Serradas P, Ravel D, Portha B. Effect of gliclazide treatment on insulin secretion and beta-cell mass in non-insulin dependent Goto-kakisaki rats. Eur J Pharmacol 1998;361:243-51.

El-Baz FK, Khalil WKB, Booles HF, Aly HF, Ali GH. Dunaliella salina suppress oxidative stress, alterations in the expression of pro-apoptosis and inflammation related genes induced by STZ in diabetic rats. Int J Pharm Sci Rev Res 2016;38:219-26.

Valtonen P, Karppi J, Nyyssonen K, Valkonen VP, Halonen T, Punnonen K. Comparison of HPLC method and commercial ELISA assay for asymmetric dimethylarginine (ADMA) determination in human serum. J Chromatogr B 2005;15;828:97-102.

Fischer BE, Thomas KB, Dorner F. von Willebrand factor: measuring its antigen or function? Correlation between the level of antigen, activity, and multimer size using various detection systems. Thromb Res 1998;91:39-40.

Hoffman P, Rauova D, Bezakova L, Oblozinsky M, Mikus P. HPLC method for determination of lipoxygenase positional specific products. J Pharm Biomed Anal 2013;84:53-8.

Anthon GE, Barrett DM. Colorimetric Method for the determination of lipoxygenase activity. J Agri Food Chem 2001;49:32-7.

Puchades Y, Ojalvo AG, GarcíaY,Chinea G, Gerónimo H, Vispo NS. Identification of peptide mimics of the epitope recognized by CB-EGF1, a monoclona-lantibody EGF specific. Biotecnol Apl 2005;22:203-6.

Elsinghorst EA. Measurement of invasion by gentamicin resistance. Methods Enzymol 1994; 236:405-20.

Drury RA, Wallington EA. Carleton's Histology Technique, 4th Edn, Oxford University Press, New York, 1980;653-61.

Srinivasan S, Muruganathan U. Antidiabetic efficacy of citronellol, a citrus monoterpene by ameliorating the hepatic key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Chem Biol Interact 2016;250:38-46.

Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. ADMA, cardiovascular disease and diabetes. Diabetes Res Clin Pract 2008;825:s122-s6.

Schnabel R, Blankenberg S, Lubos E, Lackner KJ, Rupprecht HJ, Espinola-Klein C Jachmann N, Post F, Peetz D, Bickel C, Cambien F, Tiret L, MunzelT. Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 2005; 97:53-9.

Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 2007;30:1834-9.

Lajer M, Tarnow L, Jorsal A, Teerlink T, Parving HH, Rossing P. Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care. 2008;31:747-52.

Duckelmann C, Mittermayer F, Haider DG, Altenberger J, Eichinger J, Wolzt M. Asymmetric dimethylarginine enhances cardiovascular risk prediction in patients with chronic heart failure. Arterioscl Throm Vas Biol 2007;27:2037-42.

Malecki MT, Undas A, Cyganek K, Mirkiewicz-Sieradzka B, Wolkow P, Osmenda G, Walus-Miarka M, Guzik TJ, Sieradzki J. Plasma asymmetric dimethyl arginine (ADMA) is associated with retinopathy in type 2 diabetes. Diabetes Care 2007; 30:2899-901.

Ostergard T, Nyholm B, Hansen TK, Rasmussen LM, Ingerslev J, Sorensen KE, Botker HE, Saltin B, Schmitz O. Endothelial function and biochemical vascular markers in first-degree relatives of type 2 diabetic patients: the effect of exercise training. Metabolism 2006;55:1508-15.

Natali A, Toschi E, Baldeweg S, Ciociaro D, Favilla S, Sacca L, Ferrannini E. Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes. Diabetes 2006; 55:1133-40.

Singla S, Kumar A, Singla M. Role of epidermal growth factor in healing of diabetic foot ulcers. Indian J Surg 2012;74(6):451-55.

Das UN. Arachidonic acid and lipoxin A4 as possible endogenous anti-diabetic molecules. Prostaglandins Leukot Essent Fatty Acids 2013; 88:201-10.

Naito Y, Uchiyama K, Aoi W, Hasegawa G, Nakamura N, Yoshida N, Maoka T, Takahashi J, Yoshikawa T. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors 2004;20:49-59.

Kurashige M, Okimasu E, Inoue M, Utsumi K. Inhibition of oxidative injury of biological membranes by astaxanthin. Physiol Chem Phys Med NMR. 1990; 22:27-38.

Jewell C, O’Brien N. Effect of dietary supplementation with carotenoids on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of the rat. Br J Nutr 1999; 81:235-42.



How to Cite

FAROUK K EL-BAZ, and H. F. Aly. “AMELIORATING THE METABOLIC DISORDER IN STREPTOZOTOCIN-INDUCED DIABETIC RATS BY HAEMATOCOCCUS PLUVIALIS EXTRACT”. Asian Journal of Pharmaceutical and Clinical Research, vol. 10, no. 6, June 2017, pp. 72-77, doi:10.22159/ajpcr.2017.v10i6.17785.



Original Article(s)

Most read articles by the same author(s)