Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice

Yuwen Ting; Yi-Shiou Chiou; Yike Jiang; Min-Hsiung Pan; Zhengyu Lin; Qingrong Huang

doi:10.1016/j.foodres.2015.04.031

Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice

Food Res Int. 2015 Aug:74:140-150. doi: 10.1016/j.foodres.2015.04.031. Epub 2015 Apr 24.

Authors

Yuwen Ting¹, Yi-Shiou Chiou², Yike Jiang¹, Min-Hsiung Pan², Zhengyu Lin¹, Qingrong Huang³

Affiliations

¹ Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA.
² Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
³ Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA. Electronic address: qhuang@aesop.rutgers.edu.

PMID: 28411978
DOI: 10.1016/j.foodres.2015.04.031

Abstract

Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging group of bioactive compounds with wide arrays of disease prevention functionalities. To understand the potential oral toxicity, tangeretin, being one of the most abundant polymethoxyflavones from natural sources, was used as model compound for the safety evaluation. Acute oral toxicity study was conducted using both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of tangeretin in oil suspension from single gavage administration. No evidence of death was observed during 14-day post-administration period. Alterations of the hepatic cell and clinical chemistry profile increased dose dependently and exhibited distinct injury recovery pattern among different sexes. To determine the potential safety concern related to emulsification, the sub-acute toxicity of tangeretin in emulsion was evaluated and compared with un-processed oil suspension when conducting the sub-acute toxicity study over 28days. In the sub-acute study, emulsion system did not induce a significant increase of toxicity response. However, the daily low-dose application of tangeretin showed U-shaped dose-response pattern in regard to hepatic alteration. The result from this study can serve as a good safety reference for future application of polymethoxyflavone as a functional ingredient in food.

Keywords: Acute toxicity; Emulsion; Hormesis; Lecithin; Oral; Polymethoxyflavone; Sub-acute toxicity; Tangeretin.