Exp Clin Endocrinol Diabetes 2017; 125(07): 441-448
DOI: 10.1055/s-0043-103458
Article
© Georg Thieme Verlag KG Stuttgart · New York

Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin – A Threat To Diabetes Phytotherapy

Jayjeet Majumdar
1   Department of Zoology, City College, 102/1 Raja Rammohan Sarani, Kolkata, Affiliated to University of Calcutta, West Bengal, India
,
Pratip Chakraborty
1   Department of Zoology, City College, 102/1 Raja Rammohan Sarani, Kolkata, Affiliated to University of Calcutta, West Bengal, India
,
Analava Mitra
2   School of Medical Science & Technology, Indian Institute of Technology, Kharagpur, Kharagpur, West Bengal, India
,
Nirmal kumar Sarkar
3   Department of Biological Sciences, Presidency University, Kolkata, West Bengal, India
,
Supriti Sarkar
1   Department of Zoology, City College, 102/1 Raja Rammohan Sarani, Kolkata, Affiliated to University of Calcutta, West Bengal, India
› Author Affiliations
Further Information

Publication History

received 16 November 2016
revised 01 February 2017

accepted 10 February 2017

Publication Date:
13 April 2017 (online)

Abstract

Introduction

Fenugreek (Trigonella foenum graecum), a medicinal herb with potent antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT (hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have important role in normal and type-1 diabetic subjects.

Materials and Methods

FSE (confirmed to contain trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks. Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum levels of TRH, TSH (Thyroid stimulating hormone), fT3, fT4, insulin, leptin, glucose; thyroperoxidase activity and growth of thyroid gland, food intake, adiposity index were also studied

Results

FSE significantly down regulated prepro-TRH mRNA expression; decreased serum TRH, TSH, fT3, fT4 levels, and regressed thyroid gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed control and diabetic rats. FSE decreased (p<0.005–0.001) adiposity index and leptin secretion, increased food intake and body weight in all FSE-fed rats.

Conclusion

FSE improved insulin secretion, decreased glucose level but impaired HPT axis in diabetic rats, indicating insulin-independent central hypothyroidism. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal actions raises questions whether it can be safely used to treat diabetes and/or hyperthyroidism as was suggested by many workers.

 
  • References

  • 1 The WHO expert committee on diabetes mellitus, Technical Report Series 646. Geneva and World Health Organization 1980
  • 2 Elder C. Ayurveda for diabetes mellitus: A review of the biomedical literature. Alt Ther in Health and Med 2004; 10: 44
  • 3 El-Wakf AM, Hassan HA, Mahmoud AZ. et al. Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats. Cytotechnology 2015; 67: 437-447
  • 4 Abdel Barry JA, Abdel-Hassan IA, Jawad AM. Hypoglycaemic effect of aqueous extract of the leaves of Trigonella foenum-graecum in healthy volunteers. East Mediterr Health J 2000; 6: 83-88
  • 5 Haritha C, Reddy AG, Reddy YR. et al. Evaluation of protective action of fenugreek, insulin and glimepiride and their combination in diabetic Sprague Dawley rats. J of Natural Sci, Biol and Med 2013; 4: 207
  • 6 Moiseyuk IV, Derkach KV, Shpakov AO. Functional activity of thyroid gland in male rats with acute and mild streptozotocin diabetes. J of Evolutionary Biochem and Physiol 2014; 50: 310-320
  • 7 Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clin Endocrinology 2011; 75: 1-9
  • 8 Costa-e-Sousa RH, Hollenberg AN. Minireview: The neural regulation of the hypothalamic-pituitary-thyroid axis. Endocrinology 2012; 153: 4128-4135
  • 9 Kosova F, Sepici-Dincel A, Engin A. et al. The thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats. Endocrine 2008; 33: 317-322
  • 10 Huerta MG. Adiponectin and leptin: Potential tools in the differential diagnosis of pediatric diabetes?. Reviews in Endocine and Metabolic Disorders 2006; 7: 187-196
  • 11 Al-Habori M, Raman A, Lawrence MJ. et al. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. J of Diabetes Res 2001; 2: 91-99
  • 12 Shah S, Bodhankar S, Bhonde R. et al. Regenerative potential of pancreata in alloxan induced diabetic mice by 4-hydroxyisoleucine, comparison with pioglitazone. Int J Integr Biol 2009; 5: 136
  • 13 Panda S, Biswas S, Kar A. Trigonelline isolated from fenugreek seed protects against isoproterenol-induced myocardial injury through down-regulation of Hsp27 and αB-crystallin. Nutrition 2013; 29: 1395-1403
  • 14 Leopoldo AS, Lima-Leopoldo AP, Nascimento AF et al. Classification of different degrees of adiposity in sedentary rats. Brazilian J of Med and Biol Res. 2016; 49
  • 15 Trinder T. Determination of glucose in blood using glucose oxidase with alternate oxygen acceptor. Annals of Clin Biochem 1969; 6: 24
  • 16 Chomzynski P, Mackey K. Modification of the TRI reagent procedure for isolation of RNA from polysaccharide-and proteoglycan-rich sources. Biotechniques 1995; 19: 942-945
  • 17 Bhattacharya S, Datta AG. A comparative study of the peroxidases from thyroid glands of pigeon (Columba livia domestica) and common myna (Acridotheres tristis). Comp Biochem and Physiol Part B: Comp Biochem 1971; 40: 139-145
  • 18 Alvarez-Salas E, Alcántara-Alonso V, Matamoros-Trejo G. et al. de Gortari P. Mediobasal hypothalamic and adenohypophyseal TRH-degrading enzyme (PPII) is down-regulated by zinc deficiency. Int J Dev Neurosci 2015; 46: 115-124
  • 19 Nikrodhanond AA, Ortiga-Carvalho TM, Shibusawa N. et al. Dominant role of thyrotropin-releasing hormone in the hypothalamic-pituitary-thyroid axis. J of Biol Chem 2006; 281: 5000-5007
  • 20 Chiamolera MI, Wondisford FE. Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology 2009; 150: 1091-1096
  • 21 Bestetti GE, Reymond MJ, Perrin IV. et al. Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands. Virchows Archiv B 1987; 53: 69-78
  • 22 Fekete C, Singru PS, Sanchez E. et al. Differential effects of central leptin, insulin, or glucose administration during fasting on the hypothalamic-pituitary-thyroid axis and feeding-related neurons in the arcuate nucleus. Endocrinology 2006; 147: 520-529
  • 23 Schultes B, Oltmanns KM, Kern W. et al. Acute and prolonged effects of insulin-induced hypoglycemia on the pituitary-thyroid axis in humans. Metabolism 2002; 51: 1370-1374
  • 24 Fliers E, Kalsbeek A, Boelen A. Mechanisms in Endocrinology: Beyond the fixed setpoint of the hypothalamus–pituitary–thyroid axis. European Journal of Endocrinology 2014; 171: R197-R208
  • 25 Guo F, Bakal K, Minokoshi Y. et al. Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo. Endocrinology 2004; 145: 2221-2227
  • 26 Cammisotto PG, Bukowiecki LJ. Mechanisms of leptin secretion from white adipocytes. American Journal of Physiology-Cell Physiology 2002; 283: C244-C250
  • 27 Amitani M, Asakawa A, Amitani H. et al. The role of leptin in the control of insulin-glucose axis. Front in Neurosci 2013; 7: 51
  • 28 Ahima RS, Flier JS. Leptin. Annual Rev of Physiol 2000; 62: 413-437
  • 29 Boustany CM, Bharadwaj K, Daugherty A. et al. Cassis LA. Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension. American J of Physiol-Regulatory, Integrat and Comp Physiol 2004; 287: R943-R949
  • 30 Zimmermann-Belsing T, Brabant G, Holst JJ. et al. Circulating leptin and thyroid dysfunction. Euro J of Endocrinology 2003; 149: 257-271
  • 31 Ghorbani A, Rajaei Z, Zendehbad SB. Effects of fenugreek seeds on adipogenesis and lipolysis in normal and diabetic rats. Pak J of Biol Sci 2014; 17: 523
  • 32 Calvino C, Souza LL, Costa-e-Sousa RH. et al. Hypothyroidism reduces ObRb–STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action. J of Endocrinology 2012; 215: 129-135
  • 33 Tahiliani P, Kar A. The combined effects of Trigonella and Allium extracts in the regulation of hyperthyroidism in rats. Phytomed 2003; 10: 665-668
  • 34 Vijayakumar MV, Bhat MK. Hypoglycemic effect of a novel dialysed fenugreek seeds extract is sustainable and is mediated, in part, by the activation of hepatic enzymes. Phyto Res 2008; 22: 500-505