PRENATAL DEVELOPMENTAL TOXICITY EVALUATION OF LOW MOLECULAR WEIGHT GALACTOMANNANS BASED STANDARDIZED FENUGREEK SEED EXTRACT DURING ORGANOGENESIS PERIOD OF PREGNANCY IN RATS Original Article PALLAVI DESHPANDE a , VISHWARAMAN MOHAN a , MUKUL PORE b , SHAILESH GUMASTE b , PRASAD THAKURDESAI a,* a Indus Biotech Private Limited, Kondhwa, Pune, Maharashtra, 411048, India, b Intox Pvt. Ltd., Pune, Maharashtra, 412115, India Email: prasad@indusbiotech.com Received: 01 Feb 2016 Revised and Accepted: 30 Mar 2016 ABSTRACT 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. © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ ) INTRODUCTION The increased use of botanicals or food supplements by consumers and industry has raised concerns among scientific and regulatory communities. Medicinal supplements from plants possess functional properties or health benefits. The sources of food supplement may vary from staple food plants to herbals used in folk medicine and comprise the whole plant, extracts thereof or purified components [1, 2]. The crude extracts of varieties of plants have been used in clinical practices from a long time [3] and often possess diversified phytoconstituents with unknown biological effects and can produce toxicity and drug interactions that harm to human health [4, 5]. There is a need for safety reports for a botanical extract of crude as well as purified fractions for their validated activities. Trigonella foenum-gracum (TF), known as fenugreek, is one of the most promising medicinal herbs, known from ancient times. Fenugreek seeds have known for many applications towards female health. In ancient Rome, fenugreek seeds were used to aid labor and delivery [6]. Fenugreek seeds or powder used by traditional Ayurvedic physicians to enhance milk production to breastfeeding mothers [6-8]. These benefits on female health have been attributed to unique dietary fiber components of fenugreek seeds [9]. The endosperm of the fenugreek seed is a rich source of fiber (20 %) and gum (32.4 %) [10-12], which include galactomannans (GAL). Fenugreek GAL is a group of oligosaccharides (OS) composed of mannose as the backbone with galactose as side groups in the ratio of 1:1. Fenugreek seeds contain both soluble and insoluble types of fibers [13]. The soluble dietary fiber content of fenugreek seeds is known to be responsible for health benefits such as effective restoration of both glucose and fat metabolism in DM [6, 14, 15]. The soluble dietary fiber fraction of fenugreek seeds of various compositions reported to have antidiabetic [16, 17], hypolipidemic [18, 19] and a food stabilizer properties [12]. Soluble fiber fraction of fenugreek is rich in low molecular weight galactomannans (LMWGAL) containing oligosaccharides (OS) such as raffinose (three monosaccharide units) and stachyose (five monosaccharide units). LMWGAL from fenugreek seeds demonstrated anti-hyperglycemic [15] and anabolic potential in male rats [20] and against diet-induced obesity in C57/BL6 mice [21]. Furthermore, the clinical benefit of LMWGAL based standardized fenugreek seed extract on strength and body composition in resistance-trained males has been reported [22]. A crude form of fenugreek seed powder or extract was found to be safe in many prior studies [23, 24]. Oral exposure of LMWGAL-TF is reported to be safe during acute and subchronic toxicity studies in male and female rats [25] and during 8-weeks of exposure to resistance-trained male subjects [22]. However, the safety or toxicity information of LMWGAL-TF in females during the gestational period of pregnancy is not yet known. Looking at potential applications of LMWGAL-TF for the area of female health, the study involving prenatal exposure on reproduction related parameters in pregnant mothers and fetuses is necessary. Therefore, we undertook the present study to evaluate the effects of LMWGAL-TF on pregnant female rats and their fetuses during oral exposure to female rats during the period of gestation, beginning from the implantation day as per OECD 414 guidelines, an internationally accepted procedure. MATERIALS AND METHODS Animals Adult and young nulliparous and non-pregnant healthy female Wistar rats (of 14-15 w) and adult, proven fertile male rats were inbred at the lab of INTOX Private Limited, Pune, India. Animals were housed in solid polypropylene cages with stainless steel grill tops and bedding of clean and sterilized paddy husk for at least eight days before mating. 'Nutrilab' brand extruded rodent pelleted feed (M/s Provimi Animal Nutrition India Pvt. Ltd., Bangalore) and filtered water were provided ad libitum. During the entire study, International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 5, 2016