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Arzneimittelforschung 2009; 59(3): 129-134
DOI: 10.1055/s-0031-1296375
Lipid Reducers
Editio Cantor Verlag Aulendorf (Germany)

Antioxidative and Lipid Lowering Effects of 7,8-Dihydroxy-3-(4-methylphenyl) Coumarin in Hyperlipidemic Rats

Basak Yuce
1   Marmara University, Faculty of Science and Letters, Department of Chemistry, Goztepe, Istanbul, (Turkey)
,
Ozkan Danis
1   Marmara University, Faculty of Science and Letters, Department of Chemistry, Goztepe, Istanbul, (Turkey)
,
Ayse Ogan
1   Marmara University, Faculty of Science and Letters, Department of Chemistry, Goztepe, Istanbul, (Turkey)
,
Goksel Sener
2   Marmara University, Faculty of Pharmacy, Department of Pharmacology, Hayderpasa, Istanbul, (Turkey)
,
Mustafa Bulut
1   Marmara University, Faculty of Science and Letters, Department of Chemistry, Goztepe, Istanbul, (Turkey)
,
Aysen Yarat
3   Marmara University, Faculty of Dentistry, Department of Basic Medical Science, Nisantasi, Istanbul, (Turkey)
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2011 (online)

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Abstract

In this study, 7,8-dihydroxy-3-(4-methylphenyl) coumarin (DHMPC), a new coumarin derivative, was tested for the first time to determine whether it had any antioxidant and lipid lowering effects. Hypercholesterolemia was induced by feeding rats with a high cholesterol diet for 17 days. The lipid lowering and antioxidant effects of DHMPC were compared with those of hesperidin (CAS 520-26-3) and rutin (CAS 153-18-4), which have been pharmacologically determined as potential lipid lowering and antioxidant agents. DHMPC significantly decreased serum total cholesterol levels but not as efficient as hesperidin. When the ratios of high density lipoprotein-cholesterol (HDL-cholesterol) to total cholesterol were evaluated, the most significant changes were observed in DHMPC and rutin treatments. The results of serum triglyceride levels indicate that DHMPC and hesperidin did not significantly decrease triglyceride level when compared to rutin group but prevented it to rise. Serum malondialdehyde (MDA) levels increased as expected in high cholesterol diet groups but no significant decrease was observed for serum MDA levels in all treated groups. In contrast to serum MDA levels, liver homogenates MDA levels decreased in all treated groups but a considerable decrease was not observed for DHMPC treated group. Liver homogenates glutathione (GSH) levels drastically decreased in hyperlipidemic group and increased in all treated groups. As a conclusion DHMPC displayed both antioxidant and lipid lowering effects and can be a candidate drug for further studies.

Key words

Antioxidants - CAS 153-18-4 - CAS 520-26-3 - Coumarin derivatives - 7,8-Dihydroxy-3-(4-methylphenyl) coumarin - Flavonoids - Hesperidin - Lipid lowering agents - Rutin
 

  • References

  • 1 Hertog G, Hollman P, Katan M. Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. J Agric Food Chem. 1992; 40: 2379-2383
    CrossrefPubMedGoogle Scholar
  • 2 Santos KF, Oliveira TT, Nagem TJ, Pinto AS, Oliveira MG. Hypolipidemic effects of naringenin, rutin, nicotinic acid and their associations. Pharmacol Res. 1999; 40: 493-496
    CrossrefPubMedGoogle Scholar
  • 3 Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory Properties of Plant Flavonoids. Effects of Rutin, Quercetin and Hesperidin on Adjuvant Arthritis in Rat. Il Farmaco. 2001; 56: 683-687
    CrossrefPubMedGoogle Scholar
  • 4 Gao Z, Xu H, Chen X, Chen H. Antioxidant status and mineral contents in tissues of rutin and baicalin fed rats. Life Sci. 2003; 73: 1599-1607
    CrossrefPubMedGoogle Scholar
  • 5 Kostova I. Synthetic and natural coumarins as cytotoxic agents. Anticancer Agents Med Chem. 2005; 5: 29-46
    CrossrefPubMedGoogle Scholar
  • 6 Keating GJ, O’Kennedy R. The chemistry and occurrence of coumarins. In: O’Kennedy R, Thornes RD. eds. Coumarins: Biology, Applications and Mode of Action Chichester: John Wiley & Sons.; 1997: 23-66
    Google Scholar
  • 7 O’Reilly RA, Aggeler PA, Hoag MS, Leong L. Studies on the coumarin anticoagulant drugs: The assay of warfarin and its biological application. Thromb Haemost. 1962; 8: 82-95
    PubMedGoogle Scholar
  • 8 Tyagi YK, Kumar A, Raj HG, Vohra P, Gupta G, Kumari R et al. Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity. Eur J Med Chem. 2005; 40: 413-420
    CrossrefPubMedGoogle Scholar
  • 9 Paya M, Goodwin PA, De Las Heras B, Hoult JR. Superoxide Scavenging Activity in Leucocytes and Absence of Cellular Toxicity of a Series of Coumarins. Biochem Pharmacol. 1994; 48: 445-451
    CrossrefPubMedGoogle Scholar
  • 10 Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN. Natural and synthetc coumarin derivatives with anti-inflammatory/antoxidant activities. Curr Pharm Des. 2004; 10: 3813-3833
    CrossrefPubMedGoogle Scholar
  • 11 Kostova I. Synthetic and natural coumarins as antioxidants. Mini Rev Med Chem. 2006; 6: 365-374
    CrossrefPubMedGoogle Scholar
  • 12 Park SY, Bok SH, Jeon SM, Park YB, Lee SJ, Jeong TS et al. Effect of rutin and tannic acid supplements on cholesterol metabolism in rats. Nutr Res. 2002; 22: 283-295
    CrossrefPubMedGoogle Scholar
  • 13 Kim HK, Jeong TS, Lee MK, Park YB, Choi MS. Lipid-lowering efficacy of hesperedin metabolites in high-cholesterol fed rats. Clin Chim Acta. 2003; 327: 129-137
    CrossrefPubMedGoogle Scholar
  • 14 Buu-Hoi NP, Saint-Ruf G, Lobert B. Oxygen heterocycles. Part XIV. Hydroxylated 3-aryl- and 3-pyridyl-coumarins. J Chem Soc C. 1969; 2069-2070
    PubMedGoogle Scholar
  • 15 Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310
    PubMedGoogle Scholar
  • 16 Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82: 70-77
    CrossrefPubMedGoogle Scholar
  • 17 Cirico TL, Omaye ST. Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation. Food Chem Toxicol. 2006; 44: 510-516
    PubMedGoogle Scholar
  • 18 Cho J. Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperedin. Arch Pharm Res. 2006; 29: 699-706
    CrossrefPubMedGoogle Scholar
  • 19 Florek E, Ignatowicz E, Wrzosek J, Piekoszewski W. Effect of rutin on total antioxidant status of rats exposed to cigarette smoke. Pharmacol Rep. 2005; 57: 84-89
    PubMedGoogle Scholar
  • 20 Hoult JRS, Paya M. Pharmacological ve biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen Pharmacol. 1996; 27 (4) 713-22
    CrossrefPubMedGoogle Scholar
  • 21 Kawaguchi K, Mizuno T, Aida K, Uchino K. Hesperidin as an inhibitor of lipase from porcin pancreas and Pseudomanas. Biosci Biotechnol Biochem. 1997; 61: 102-104
    CrossrefPubMedGoogle Scholar
  • 22 Monforte MT, Trovato A, Kirjavainen S, Forestieri AM, Galati EM, Lo Curto RB. Biological effects of hesperidin, a citrus flavonoid (note II): hypolipidemic activity on experimental hypercholesterolemia in rat. Farmaco. 1995; 50: 595-599
    PubMedGoogle Scholar
  • 23 Danis O, Ogan A, Bulut M, Sener G Investigation of the hydroxycoumarin and aminocoumarin derivatives effects on blood coagulation time. 5th National Congress of Thrombosis, Homeostasis and Angiology. 2004 May 07–09; Istanbul, Grand Cevahir Hotel.
    PubMed
  • 24 Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. Plasma malondialdehyde as biomarker for oxidative stres: reference interval and effects of life-style factors. Clin Chem. 1997; 43 (7) 1209-1214
    CrossrefPubMedGoogle Scholar
  • 25 Manach C, Morand C, Demigné C, Texier O, Régérat F, Rémésy C. Bioavailability of rutin and quercetin in rats. FEBS Letter. 1997; 409: 12-16
    CrossrefPubMedGoogle Scholar
  • 26 Tirkey N, Pilkhwal S, Kuhad A, Chopra K. Hesperidin, a citrus bioflavonoid decreases the oxidative stres produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacology. 2005; 5: 1-8
    PubMedGoogle Scholar