Pallavi Deshpande, Vishwaraman Mohan, Mukul Pore, Shailesh Gumaste, Prasad Thakurdesai


Objective: To evaluate the prenatal developmental toxicity of low molecular weight galactomannans based standardized fenugreek seed extract (LMWGAL-TF).

Methods: Rats received oral administration of LMWGAL-TF (250, 500 and 1000 mg/kg) during the period of gestation from day 5 (implantation day)–19 (1 d before expected day of parturition) post conception. Maternal, embryo, and fetal toxicity parameters were evaluated.

Results: LMWGAL-TF exposure did not produce maternal (clinical observations, body weight gain, food intake) and embryo–fetal toxicity. Occasional skeletal and visceral malformations, unrelated to the treatments, were seen in both LMWGAL-TF-treated and vehicle control (VC) groups.

Conclusion: Oral exposure of LMWGAL-TF during the prenatal period did not induce significant maternal and embryo–fetal toxicity up to a dose of 1000 mg/kg in rats. The dose of 1000 mg/kg was considered as NOAEL for LMWGAL-TF.

Keywords: Developmental toxicity, Low molecular weight galactomannans, Standardized fenugreek seed extract, OECD Test No. 414, Reproductive system, Rat.


Developmental toxicity; low molecular weight galactomannans; standardized fenugreek seed extract; OECD No. 414; Reproductive system; rat

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Schilter B, Andersson C, Anton R, Constable A, Kleiner J, O'Brien J, et al. Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food Chem Toxicol 2003;41:1625-49.

Walker R. Criteria for risk assessment of botanical food supplements. Toxicol Lett 2004;149(1-3):187-95.

Banerjee R, Verma AK, Das AK, Rajkumar V, Shewalkar AA, Narkhede HP. Antioxidant effects of broccoli powder extract in goat meat nuggets. Meat Sci 2012;91:179-84.

Palmer ME, Haller C, McKinney PE, Klein-Schwartz W, Tschirgi A, Smolinske SC, et al. Adverse events associated with dietary supplements: an observational study. Lancet 2003;361(9352):101-6.

Pittler M, Ernst E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003;18:451-71.

Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev 2003;8:20-7.

Patil SP, Niphadkar PV, Bapat MM. Allergy to fenugreek (Trigonella foenum graecum). Ann Allergy Asthma Immunol 1997;78:297-300.

Schaffir J, Czapla C. Survey of lactation instructors on folk traditions in breastfeeding. Breastfeed Med 2012;7:230-3.

Madar Z, Stark AH. New legume sources as therapeutic agents. Br J Nutr 2002;88 Suppl 3:S287-92.

Sharma R. Effect of fenugreek seeds and leaves on blood glucose and serum insulin responses in human subjects. Nutr Res 1986;6:1353-64.

Sharma R, Raghuram T, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:301-6.

Meghwal M, Goswami T. A review on the functional properties, nutritional content, medicinal utilization and potential application of fenugreek. J Food Process Technol 2012:3:181.

Madar Z, Shomer I. Polysaccharide composition of a gel fraction derived from fenugreek and its effect on starch digestion and bile acid absorption in rats. J Agric Food Chem 1990;38:1535-9.

Raju J, Gupta D, Rao AR, Yadava PK, Baquer NZ. Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Mol Cell Biochem 2001;224(1-2):45-51.

Kamble H, Kandhare A, Bodhankar S, Mohan V, Thakurdesai PA. Effect of low molecular weight galactomannans from fenugreek seeds on animal models of diabetes mellitus. Biomed Aging Pathol 2013;3:145-51.

Hannan JM, Ali L, Rokeya B, Khaleque J, Akhter M, Flatt PR, et al. Soluble dietary fiber fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Br J Nutr 2007;97:514-21.

Al-Habori M, Raman A, Lawrence MJ, Skett P. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A. Int J Exp Diabesity Res 2001;2:91-9.

Boban PT, Nambisan B, Sudhakaran PR. Hypolipidaemic effect of chemically different mucilages in rats: a comparative study. Br J Nutr 2006;96:1021-9.

Venkatesan N, Devaraj SN, Devaraj H. A fibre cocktail of fenugreek, guar gum, and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats. Mol Cell Biochem 2007;294(1-2):145-53.

Aswar U, Mohan V, Bhaskaran S, Bodhankar SL. Study of galactomannan on androgenic and anabolic activity in male rats. Pharmacologyonline 2008;2:56-65.

Kandhare A, Bodhankar SL, Mohan V, Thakurdesai PA. Prophylactic efficacy and possible mechanisms of oligosaccharides based standardized fenugreek seed extract on high-fat-diet-induced insulin resistance in C57BL/6 mice. J Appl Pharm Sci 2015;5:35-45.

Poole C, Bushey B, Foster C, Campbell B, Willoughby D, Kreider R, et al. The effects of a commercially available botanical supplement on strength, body composition, power output, and hormonal profiles in resistance-trained males. J Int Soc Sports Nutr 2010;7:34.

Narasimhamurthy K, Viswanatha S, Ramesh B. Acute and subchronic toxicity assessment of debitterized fenugreek powder in the mouse and rat. Food Chem Toxicol 1999;37:831-8.

Muraki E, Hayashi Y, Chiba H, Tsunoda N, Kasono K. Dose-dependent effects, safety and tolerability of fenugreek in diet-induced metabolic disorders in rats. Lipids Health Dis 2011;10:240.

Bodhankar SL, Kandhare A, Mohan V, Thakudesai PA. Toxicological evaluations of the low molecular weight galactomannans from fenugreek seeds [OP-9]. XXXIII Annual Conference of Society of Toxicology (STOX). Mathura, India; 2013.

OECD. Test No. 414: Prenatal Development Toxicity Study. OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects. Paris: OECD Publishing; 2001.

Burdan F, Szumiło J, Dudka J, Klepacz R, Błaszczak M, Solecki M, et al. Morphological studies in modern teratological investigations. Folia Morphol (Praha) 2005;64:1-8.

Salewski E. Färbemethode zum makroskopischen nachweis von Implantationsstellen am Uterus der ratte. Naunyn-Schmiedeberg's Arch Pharmacol 1964;247:367.

Monie IW, Kho KG, Morgan J. Dissection procedures for rat foetuses permitting alizarin red staining of skeleton and histological study of viscera. 1965. p. 163-73.

Taylor P. Practical Teratology. London: Academic Press; 1986.

Kassem A, Al-Aghbari A, Molham AH, Al-Mamary M. Evaluation of the potential antifertility effect of fenugreek seeds in male and female rabbits. Contraception 2006;73:301-6.

Khalki L, M’hamed SB, Bennis M, Chait A, Sokar Z. Evaluation of the developmental toxicity of the aqueous extract from Trigonella foenum-graecum (L.) in mice. J Ethnopharmacol 2010;131:321-5.

Mital N, Gopaldas T. Effect of fenugreek (Trigonella foenum graecum) seed based diets on the birth outcome in albino rats. Nutr Rep Int 1986;33:363-9.

Khalki L, Bennis M, Sokar Z, Ba-M’hamed S. The neurobehavioral developmental effects of fenugreek seeds on prenatally exposed mice. J Ethnopharmacol 2012;139:672-7.

Kamal R, Yadav R, Sharma J. Efficacy of the steroidal fraction of fenugreek seed extract on fertility of male albino rats. Phytother Res 1993;7:134-8.

Skalli S. Malformations associées à la prise de fenugrec au cours de la grossesse. Bulletin d’informations de pharmacovigilance; 2006. p. 3.

Mittal N, Gopaldas T. Effect of fenugreek (Trigonella foenum graceum) seeds based on the birth outcome in albino rats. Nutr Reproduction Int 1986;33:362-9.

Mittal N, Gopaldas T. Effect of fenugreek (Trigonella foenum-graecum) seed based diets on the lactational performance in albino rats. Nutr Report Int 1986;33:477-84.

Curry LL, Roberts A, Brown N. Rebaudioside a: two-generation reproductive toxicity study in rats. Food Chem Toxicol 2008;46:S21-S30.

Planas GM, Kuć J. Contraceptive properties of Stevia rebaudiana. Science 1968;162:1007.

Melis MS. Effect of crude extract of Stevia rebaudiana on renal water and electrolytes excretion. Phytomedicine 1999;6:247-50.

Melis MS. Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol 1999;67:157-61.

Melis MS. Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal effects. J Ethnopharmacol 1995;47:129-34.

Melis MS. A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats. Braz J Med Biol Res 1996;29:669-75.

Taloubi L, Rhouda H, Belahcen A, Smires N, Thimou A, Mdaghri AA. An overview of plants causing teratogenicity: Fenugreek (Trigonella foenum graecum). Int J Pharm Sci Res 2013;4:516.

Center for Drug Evaluation and Research. Guidance for Industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. US Department of Health and Human Services, Food and Drug Administration; 2005.

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Developmental toxicity; low molecular weight galactomannans; standardized fenugreek seed extract; OECD No. 414; Reproductive system; rat



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International Journal of Pharmacy and Pharmaceutical Sciences
Vol 8, Issue 5, 2016 Page: 248-253

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Authors & Affiliations

Pallavi Deshpande

Vishwaraman Mohan

Mukul Pore

Shailesh Gumaste

Prasad Thakurdesai
Indus Biotech Private Limited, Kondhwa, Pune, Maharashtra, 411048, India

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