Horm Metab Res 2011; 43(3): 188-193
DOI: 10.1055/s-0031-1271621
Animals

© Georg Thieme Verlag KG Stuttgart · New York

Periplogenin, Isolated from Lagenaria siceraria, Ameliorates L-T4-induced Hyperthyroidism and Associated Cardiovascular Problems

S. Panda1 , A. Kar1
  • 1School of Life Sciences, Devi Ahilya University, Indore, M. P., India
Further Information

Publication History

received 02.08.2010

accepted after second revision 22.12.2010

Publication Date:
01 February 2011 (online)

Abstract

The importance of glycoside in the regulation of thyroid dysfunction is not well understood. In the present investigation, effects of periplogenin-3-O-D-glucopyranosyl (1→6)(1→4)-D-cymaropyranoside, isolated from the vegetable, Lagenaria siceraria, in L-thyroxine (L-T4)-induced hyperthyroidism and in related cardiovascular abnormalities have been revealed in Wistar albino rats. L-T4 (500 μg/kg, s. c./d) administration for 12 days significantly increased serum concentrations of thyroxine (T4), triidothyronine (T3), and hepatic 5′-deiodinase I (5′-DI) activity with a parallel increase in lipid peroxidation (LPO) in different organs such as heart, liver and kidney; serum glucose and insulin concentrations and a decrease in cardiac Na+-K+-ATPase activity as well as serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and triglycerides. Most of these adverse effects were reversed following the administration of isolated periplogenin. However, out of its 3 different concentrations (5.0, 10, and 25 mg/kg), 5 mg/kg appeared to be the most effective one as it could nearly normalize the level of T3, glucose, insulin, Na+-K+-ATPase activity, tissue LPO and different serum lipids suggesting the protective role of periplogenin against thyrotoxicosis and associated cardiovascular problems. It appears that the periplogenin actions are mediated through its direct antithyroidal and/or LPO inhibiting properties.

References

  • 1 Ganong WF. Review of Medical Physiology. 22 nd ed. Connecticut: Appleton and Lange; 2005: 290-293
  • 2 Katzung BG. Thyroid and antithyroid drugs. In: Basic and Clinical Pharmacology, 7th ed. Stamford, Connecticut: Appleton and Lange; 1998: 619-634
  • 3 Klein I, Danzi S. Thyroid disease and the heart.  Circulation. 2008;  22 18-25
  • 4 Fater-Debska A, Gworys P, Brzezinski J, Gawor Z. Thyrometabolic disorders and heart failure.  Endokrynol Pol. 2007;  58 228-235
  • 5 Prassas I, Diamandis EP. Novel therapeutic applications of cardiac glycosides.  Nat Rev. 2008;  63 414-434
  • 6 Fadel BM, Ellahham S, Ringel MD, Lindsay Jr J, Wartofsky L, Burman KD. Hyperthyroid and Heart Disease.  Clin Cardiol. 2000;  23 402-408
  • 7 Morrow DH, Gaffney TE, Braunwald E. Studies on digitalis: Effect of autonomic innervations and of myocardial catecholamine stores upon the cardiac action of ouabain.  J Pharmacol Exp Ther. 1963;  140 236-245
  • 8 Ghule BV, Ghante MH, Saoji AN, Yeole PG. Antihyperlipidemic effect of the methanolic extract from Lagenaria siceraria (Stand) fruit in hyperlipidemic rats.  J Ethnopharmacol. 2009;  124 333-337
  • 9 Deshpande JR, Choudhari AA, Mishra MR, Meghre VS, Wadokar SG, Dorle AK. Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.  J Exp Biol. 2008;  46 234-242
  • 10 Dixit Y, Panda S, Kar A. Lagenaria siceraria Peel Extract in the regulation of Hyperthyroidism, Hyperglycemia and Lipid Peroxidation in Mice.  Int J Biomed Pharm Sci. 2008;  2 79-83
  • 11 Clausen T. Clinical and therapeutic significance of the Na+-K+ pump.  Clin Sci. 1998;  95 3-17
  • 12 Chaudary S, Ismail-Beigi F, Grick GG, Levenson R, Edelman IS. Effect of thyroid hormone on the abundance of Na-K-ATP-adenosine triphosphatase alpha-subunit messenger ribonucleic acid.  Mol Endocrinol. 1987;  1 83-89
  • 13 Muller MJ, Achesson KJ, Jequir E, Burgrer AG. Effects of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans.  Am J Physiol. 1988;  18 146-152
  • 14 Iossa S, Lionetti L, Mollica M P, Crescenzo R, Barletta A, Liverini G. Fat balance and serum leptin concentrations in normal, hypothyroid, and hyperthyroid rats.  Int J Obes Relat Metab Disord. 2001;  25 417-425
  • 15 Lei ZH, Jin ZX, Ma YL, Tai BS, Kong Q, Yahara S, Nohara T. Cardiac glycosides from Erysimum cheirantoides.  Phytochem. 1998;  49 1801-1803
  • 16 Panda S, Kar A. Regulation of hyperthyroidism by R. serpentine root extract in mice.  Phram Pharmacol Commun. 2000;  6 517-520
  • 17 Li PW, Ho CS, Swaminathan R. The chronic effects of long-term digoxin administration on Na-K-ATPase activity in rat tissues.  Int J Cardiol. 1993;  40 95-100
  • 18 Panda S, Kar A. Periplogenin-3-O-D-glucopyranosyl (1→6)-D-glucopyaranosyl-(14)-D-cymaropyranoside, isolated from Aegle marmelos protects doxorubicin induced cardiovascular problems and hepatotoxicity in rats.  Cardiovasc Therapeut. 2009;  27 108-116
  • 19 Ohkawa H, Ohishi N, Yagi K. Assays of lipid peroxides in animal tissues by thiobarbituric acid reaction.  Anal Biochem. 1979;  95 351-358
  • 20 Le Bel D, Porier GC, Beaudoin AR. A convenient method for the ATPase assay.  Anal Biochem. 1978;  85 86-89
  • 21 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin-phenol reagent.  J Biochem. 1951;  193 265-275
  • 22 Panda S, Kar A, Patil S. Soy sterols in the regulation of thyroid functions, glucose homeostasis and hepatic lipid peroxidation in mice.  Food Res Internat. 2009;  42 1087-1092
  • 23 Panda S, Kar A. Inhibition of T3 production in Levothyroxine-Treated female mice by the root extract of Convolvulus pluricaulis.  Horm Metab Res. 2001;  33 16-18
  • 24 Panda S, Kar A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5’D activity in adult male mice.  Horm Metab Res. 2003;  35 523-526
  • 25 Allian CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol.  Clin Chem. 1974;  20 470-475
  • 26 Fossati P, Lorenzo P. Serum triglycerides determination colorimetrically with an enzyme that produces hydrogen peroxide.  Clin Chem. 1982;  28 2077-2080
  • 27 Friedwald WT, Levy RI, Fredrickson DC. Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge.  Clin Chem. 1972;  18 499-502
  • 28 Trinder P. Determination of blood glucose using an oxidase-peroxidase system with non-carcinogenic chromogen.  J Clin Pathol. 1969;  22 158-161
  • 29 Yamauchi T, Yujiro M, Yasuko O. 16-Dehydroadynerigenin glycosides of Nerium odorum.  Phytochem. 1973;  12 2737-2739
  • 30 Zhang L, Xu L Z, Yang SL. Two new cardenolides from the roots of Streptocaulon griffithii.  J Asian Nat Prod Res. 2006;  8 613-617
  • 31 Tan XG, Zhang XR, Wang MK, Peng SL, Ding LS. Two new cardenolide glycosides from Biondia hemsleyana.  Chem Lett. 2002;  13 547-548
  • 32 Jennings AS, Crutchfield FL, Dratman MB. Effect of hypothyroidism and hyperthyroidism on triidothyronine production in rat liver.  Endocrinol. 1984;  114 992-997
  • 33 Panda S, Kar A. A.squamosa seed extract in the regulation of hyperthyroidism and LPO in mice: Possible involvement of quercetin.  Phyto Med. 2006;  14 799-805
  • 34 Panda S, Kar A. Amelioration of L-thyroxine induced hyperthyroidism by Coumarin (1,2-Benzopyrone) in female rats.  Clin Exp Pharmacol Physiol. 2007;  34 1217-1219
  • 35 Chopra IJ, Solomon DH, Chopra U, Wu SY, Fisher DA, Nakamura Y. Pathways of metabolism of thyroid hormones.  Recent Prog Horm Res. 1978;  34 521-567
  • 36 Gubdjorson S, Hallgrimson J, Skuldottir G. Properties of transport adenosine triphosphatase. In: Peter H, Geshaw GA, Paoethi R (eds). Arterial pollution, New York: Plenum; 1983: 101-155
  • 37 LeGrow AB, Fielding DC, Pressley TA. Stimulation of Na-K-ATPase by hypothyroidism in the thyroid gland.  J Endocrinol. 1999;  160 453-460
  • 38 Greenspan FS. The thyroid gland. In: Greenspan FS, Baxter JD eds, Englewood Cliffs, NewJersy: Prentice Hall International Inc; 1994: 160-226
  • 39 Cortizo AM, Chazenbalk GD, de-Gagliardino EE, Garcia ME, Pisarev MA, Gagliardino JJ. Thyroid hormone binding and deiodination by pancreatic islets: relationship with the in vitro effect upon insulin secretion.  Acta Endocrinol. 1987;  116 66-72
  • 40 Parmar HS, Kar A. Antiperoxidative, antithyroidal, antihyperglycemic and cardioprotective role of Citrus sinensis peel extract in male mice.  Phytother Res 22. 2007;  22 791-795
  • 41 Duntas LH. Thyroid disease and lipids.  Thyroid. 2002;  12 287-293
  • 42 Halliwell B, Gutteridge JMC. Free radicals in Biology and Medicine. 1st ed. Oxford: Clarendon Press; 1989: 88-276
  • 43 Araujo AS, Ribeiro MF, Enzveiler A, Schenkel P, Fernandes TR, Partata WA. Myocardial antioxidant enzyme activities and concentration and glutathione metabolism in experimental hyperthyroidism.  Mol Cell Endocrinol. 2006;  249 133-139
  • 44 Venditti P, Di Meo S. Thyroid hormone-induced oxidative stress.  Cell Mol Life Sci. 2006;  63 414-434

Correspondence

Dr. S. Panda

School of Life Sciences

D. A. University

Takhshila Campus

452017 Indore

India

Phone: +91/731/247 7166

Fax: +91/731/246 0830

Email: sppsunanda9@gmail.com

    >