Mutagenicity and preclinical safety assessment of the aqueous extract of Clinacanthus nutans leaves

Abstract

Context: Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking. Objective: To evaluate the adverse effects of aqueous extract of CN leaves (AECNL). Materials and methods: The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains. Results: No mortality or morbidity was found in the animals upon single and repeated dose administration. However, significant body weight loss was observed at 2000 mg/kg during sub-chronic (90 d) exposure. In addition, increased eosinophil at 500 mg/kg and decreased serum alkaline phosphatase levels at 2000 mg/kg were observed in male rats. Variations in glucose and lipid profiles in treated groups were also observed compared to control. Ames test revealed no evidence of mutagenic or carcinogenic effects at 500 μg/well of AECNL. Conclusion: The median lethal dose (LD₅₀) of the AECNL is >5000 mg/kg and the no-observed-adverse-effect level is identified to be greater than 2000 mg/kg/day in 90-d study.

• In vitro and in vivo toxicology
• OECD
• acute
• sub-acute
• sub-chronic
• LD50
• NOAEL

Acknowledgements

The authors would like to thank the Malaysian Ministry of Agriculture for providing financial support for this project, Nature Ceuticals Sdn Bhd and the School of Pharmaceutical Sciences, University Sains Malaysia for facilitating the work.

Declaration of interest

I certify that each author has contributed substantially to the submitted work and has reviewed and agreed to the submission of the manuscript. The majority of the authors who have worked on the study have no direct conflict of interests. Three authors however indirectly input to the Malaysian Ministry of Agriculture through research grants reports. These grants are awarded to Malaysian national academic institutions to focus on addressing and evaluating the pharmacological and toxicological properties of local indigenous medicinal herbs.

The Malaysia Ministry of Agriculture (grant no.: 304/PFARMASI/650622/K123), Universiti Sains Malaysia (USM) through the Research University Team (RUT) (grant no.: 1001/PFARMASI/851001) funded this project, and Universiti Sains Malaysia fellowship scheme.