Preclinical Safety Assessment of Furostanol Glycoside-Based Standardized Fenugreek Seed Extract in Laboratory Rats

ABSTRACT

The present work is aimed at studying acute oral toxicity (AOT), subchronic oral toxicity, mutagenicity, and genotoxicity of furostanol glycosides-based standardized fenugreek seed extract (Fenu-FG) using the Organization for Economic Co-operation and Development (OECD) guidelines. The AOT and subchronic (90-day repeated dose) toxicity studies were performed on Wistar rats as per OECD 423 and OECD 408 guidelines, respectively. The mutagenicity (reverse mutation assay, Ames test) and genotoxicity (mammalian chromosome aberration test) were assessed in vitro using OECD 471 and OECD 473 guidelines, respectively. At an acute oral limit dose of 2,000 mg/kg, Fenu-FG did not show any mortality or treatment-related adverse signs. Ninety days of subchronic oral administration of Fenu-FG (250, 500, or 1,000 mg/kg) in rats did not induce any treatment-related significant changes with respect to body weight, hematology, blood biochemistry, urinalysis, gross pathology, or histopathology. The no-observed-adverse-effect-level of Fenu-FG was 1,000 mg/kg/day. Furthermore, Fenu-FG did not demonstrate mutagenic potential up to a concentration of 5,000 µg/plate (Ames test) and did not induce structural chromosome aberrations up to 2,000 µg/ml (in human lymphocyte cells in vitro). In conclusion, Fenu-FG was found safe during preclinical safety assessments.

KEYWORDS:

• acute oral toxicity
• Ames test
• genotoxicity
• standardized fenugreek seed extract
• subchronic toxicity

Acknowledgments

We would like to acknowledge Intox Private Limited, Pune, India for the research services.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

The study was supported by Indus Biotech Private Limited, Pune, India.

Additional information

Notes on contributors

Pallavi Deshpande

Pallavi Deshpande, MPharm, is the assistant manager of scientific affairs at Indus Biotech Private Limited, Pune, India with research interests in toxicology and clinical studies of dietary supplements.

Vishwaraman Mohan

Vishwaraman Mohan, MSc, is the executive vice president and chief scientific officer at Indus Biotech Private Limited, Pune, India with research interests in isolation and characterization of phytochemicals for discovery of dietary supplements.

Dilip Ingavale

Dilip Ingavale, MVSc, is a scientist at Intox Private Limited, Pune, India with a research interest in toxicology.

Jyoti Mane

Jyoti Mane, MSc, is a research assistant at Intox Private Limited, Pune, India with a research interest in genotoxicity studies.

Mukul Pore

Mukul Pore, MVSc, DABT, is director of Intox Private Limited, Pune, India with research interests in a wide array of toxicological studies.

Prasad Thakurdesai, PhD

Prasad Thakurdesai, PhD, is the general manager of scientific affairs and quality assurance at Indus Biotech Private Limited, Pune, India with research interests in areas of pharmacology and toxicology of dietary supplements.