Drug Res (Stuttg) 2016; 66(12): 618-627
DOI: 10.1055/s-0042-113182
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Investigation into Iron Chelating and Antioxidant Potential of Melilotus officinalis in Iron Dextran Induced Iron Overloaded Sprague Dawley Rat Model

N. A. Sheikh
1   Department of Pharmacology, Smt. C. V. Gajera Pharmacy Mahila College, Amreli, Gujarat, India
2   Department of Pharmacology, School of Pharmacy, RK University, Rajkot, Gujarat, India
,
T. R. Desai
2   Department of Pharmacology, School of Pharmacy, RK University, Rajkot, Gujarat, India
,
P. R. Tirgar
2   Department of Pharmacology, School of Pharmacy, RK University, Rajkot, Gujarat, India
› Author Affiliations
Further Information

Publication History

received 20 March 2016

accepted 01 July 2016

Publication Date:
14 September 2016 (online)

Abstract

Excess of iron leads to generates free radicals, causes organ damage. Melilotus officinalis (Fabaceae) reported to have various pharmacological activities. It contains flavonoids and phenolic compounds which have iron chelating and antioxidant property. Hence, present study was designed to investigate the beneficial effects of different fractions of M. officinalis for the management of iron overload disease and its complications. Iron overload was induced by 6 IP injections of iron dextran (12.5 mg/100 g) uniformly distributed over the period of 30 days. The different fractions of M. officinalis were given orally and Deferoxamine (DFO) subcutaneously for 30 days. The iron chelating and various biochemical parameters were estimated on 15th and 30th day. The different fractions of M. officinalis demonstrated dose dependant in-vitro iron chelating ability. There were significant (P<0.01) iron chelating potential shows in rats treated with methanolic fraction of methanolic extract (MFME) and methanolic fraction of aqueous extract (MFAE) of M. officinalis as compared to disease control (DC) rats. The rats treated with MFME and MFAE of M. officinalis shows significant (P<0.01) antioxidant and vital organ protective effect as compared to DC rats. Better iron chelation was observed on 30th day and at higher dose (300 mg/kg) as compared to 15th day and at lower dose (150 mg/kg). The present study concludes that MFME and MFAE of M. officinalis have reversible iron chelating and antioxidant potential in rats. The study also proves the possible mechanism of action, as an iron chelator by increasing the excretion of iron in urine and feces.

 
  • References

  • 1 Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci 2014; 19: 164-174
  • 2 Pietrangelo A. Haemochromatosis. Gut 2003; 52 Suppl II ii23-ii30
  • 3 Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharm 2005; 202: 199-211
  • 4 Siddique A, Kowdley KV. Review article: The iron overload syndromes. Aliment Pharmacol Ther 2012; 35: 876-893
  • 5 Ong CK, Lim SL, Tan WC et al. Endocrine complications in transfusion dependent thalassaemia in penang hospital. Med J Malaysia 2008; 63: 109-112
  • 6 Dimitriou E, Kairis M, Sarafidou J et al. Iron overload and kidney lysosomes. Biochimica et Biophysica Acta 2000; 1501: 138-148
  • 7 Schipper HM. Neurodegeneration with brain iron accumulation – Clinical syndromes and neuroimaging. Biochimica et Biophysica Acta 2012; 1822: 350-360
  • 8 Porter JB. Practical management of iron overload. Brit J Haematol 2001; 115: 239-252
  • 9 Hatcher HC, Singh RN, Torti FM et al. Synthetic and natural iron chelators: therapeutic potential and clinical use. Future Med Chem 2009; 1: 1643-1670
  • 10 Sarkar R, Mandal N. Study of iron chelating and DNA protective activities in hydroalcoholic extract of Indian medicinal plants. Int J Pharm Bio Sci 2012; 3: 282-291
  • 11 Olabinri BM, Eniyansoro OO, Okoronkwo CO et al. Evaluation of chelating ability of aqueous extract of Tetracarpidium conophorum (African walnut) in vitro. Int J Appl Res Nat Prod 2010; 3: 13-18
  • 12 Patralekh LN, Mukherjee G. In vitro studies on antioxidant and iron-chelating activity of Enhydra fluctuans Lour. Sci Cult 2010; 76: 537-539
  • 13 Tirgar PR, Desai TR. Investigation into iron chelating activity of Triticum aestivum (wheat grass) in iron-dextran induce iron overload model of thalassaemia. J Pharm Res 2011; 4: 3066-3069
  • 14 Patel R, Tirgar P. Evaluation of beneficial effects of Medicago sativa (Alfalfa) in iron-overload conditions. J Chem Bio Phy Sci Sec B 2013; 3: 2628-2643
  • 15 Desai TR, Solanki JK, Buch P et al. Triticum aestivum (Wheatgrass) formulation: An alternate treatment for the patients with thalassemia. Ori Pharm Exp Med 2008; 7: 466-476
  • 16 Braga PC, Sasso MD, Lattuada N et al. Antioxidant activity of Melilotus officinalis extract investigated by means of the radical scavenging activity, the chemiluminescence of human neutrophil bursts and lipoperoxidation assay. J Med Plants Res 2013; 7: 358-365
  • 17 Karakas FP, Yildirim A, Turker A. Biological screening of various medicinal plant extracts for antibacterial and antitumor activities. Turk J Biol 2012; 36: 641-652
  • 18 Luminit PM, Parvu AE, Parvu M et al. Effects of Melilotus officinalis on acute inflammation. Phytother Res 2002; 16: 316-319
  • 19 Anwer MS, Shamim S, Ahmed S et al. Hypotensive activity of Melilotus officinalis (L.) Pallas. Eur J Med Series B 2015; 3: 80-85
  • 20 Nadkarni AK. Indian materia medica. 3rd ed. volume I. Mumbai: Popular Prakashan; 2007: 786
  • 21 Kirtikar KR, Basu BD. Indian medicinal plants. 2nd ed. volume I. Dehradun: International Book Distributors; 2005: 704-705
  • 22 [Anonymous] The wealth of India. A dictionary of Indian raw materials and industrial products. Volume 6 (L–M). New Delhi: CSIR; 2003: 331
  • 23 Gird CE, Duţu LE, Popescu ML et al. Experimental research regarding the active extracts, polyphenolsstandardized. Note II. Meliloti herba-pharmacognostic analysis of the raw material. Farmacia 2009; 57: 184-191
  • 24 Anwer MS, Mohtasheem M, Iqbal A et al. Chemical constituents from Melilotus officinalis. J Basic Appl Sci 2008; 4: 89-94
  • 25 Gudzenko AV, Vinogradov BA. Chemical composition of the essential oil from Melilotus officinalis (L.) Pall. World Appl Sci J 2014; 29: 171-172
  • 26 Symonowicz M, Kolanek M. Flavonoids and their properties to form chelate complexes. Biotechnol Food Sci 2012; 76: 35-41
  • 27 Ebrahimzadeh MA, Pourmorad F, Bekhradnia AR. Iron chelating activity, phenol and flavonoid content of some medicinal plants from Iran. Afr J Biotechno 2008; 7: 3188-3192
  • 28 Kokate CK. Practical Pharmacognosy. 4th ed. New Delhi: Vallabh Prakashan; 2004: 136-154
  • 29 Dinis TCP, Madeira VMC, Almeida ML. Action of phenolic derivates (acetoaminophen, salycilate and 5-aminosalycilate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 1994; 315: 161-169
  • 30 Ibrahim NG, Hoffstein ST, Freedman ML. Induction of liver cell haem oxygenase in iron-overloaded rats. Biochem J 1979; 180: 257-263
  • 31 Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematol (Am Soc Hematol Educ Program) 2001; 2001: 47-61
  • 32 Venkataram S, Rahman YE. Studies of an oral iron chelator: 1, 2 -dimethyl- 3 -hydroxy-pyrid-4-one I. Iron excretion in rats: development of a new rapid microwave method for iron analysis in faeces. Brit J Haematol 1990; 75: 274-277
  • 33 Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170-3175
  • 34 Aebi H. Catalase. In: Bergmeyer HV. (ed.). Methods in enzyme analysis. Volume II. New York: Academic press; 1974: 674-684
  • 35 Beutler E, Duron O, Kelly BM. Improved method for the determination of blood Glutathione. J Lab Clin Med 1963; 61: 882-888
  • 36 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
  • 37 Bancroft JD, Gamble M. Theory and practice of histological techniques. 6th ed. Edinburgh New York: Churchill Livingstone; 2008: 121-134
  • 38 Ghasemzadeh A, Ghasemzadeh N. Flavonoids and phenolic acids: Role and biochemical activity in plants and human. J Med Plants Res 2011; 5: 6697-6703
  • 39 Pourmorad F, Hosseinimehr SJ, Shahabimajd N. Antioxidant activity, phenol and flavonoid contents of some selected Iranian medicinal plants. Afr J Biotechnol 2006; 5: 1142-1145
  • 40 Nam H, Knutson MD. Effect of dietary iron deficiency and overload on the expression of ZIP metal-ion transporters in rat liver. Biometals 2012; 25: 115-124
  • 41 Fischer R, Longo F, Nielsen P et al. Monitoring long-term efficacy of iron chelation therapy by deferiprone and desferrioxamine in patients with beta thalassaemia major: application of SQUID biomagnetic liver susceptometry. Brit J Haematol 2003; 121: 938-948
  • 42 Bacon BR, Adams PC, Kowdley KV et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 328-343
  • 43 Hussein SA, Azab ME, El-Shall SK. Protective effect of Curcumin on antioxidant defense system and oxidative stress in liver tissue of iron overloading rats. Asian J Clin Nutr 2014; 6: 1-17
  • 44 Aziza SAH, Azab ME, El-Shall SK. Ameliorating role of Rutin on oxidative stress induced by iron overload in hepatic tissue of rats. Pak J Biol Sci 2014; 17: 964-977
  • 45 Hershko C. Determinants of fecal and urinary iron excretion in desferrioxamine treated rats. Blood 1978; 51: 415-423
  • 46 Heli H, Mirtorabi S, Karimian K. Advances in iron chelation: an update. Expert Opin Ther Patents 2011; 21: 819-856
  • 47 Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95: 26-36