In vitro safety pharmacology evaluation of 2-hydroxybenzylamine acetate

Food Chem Toxicol. 2018 Nov:121:541-548. doi: 10.1016/j.fct.2018.09.047. Epub 2018 Sep 22.


2-hydroxybenzylamine (2-HOBA), a compound found in buckwheat, is a potent scavenger of reactive γ-ketoaldehydes, which are increased in diseases associated with inflammation and oxidative stress. While the potential of 2-HOBA is promising, studies were needed to characterize the safety of the compound before clinical trials. In a series of experiments, the risks of 2-HOBA-mediated mutagenicity and cardio-toxicity were assessed in vitro. The effects of 2-HOBA on the mRNA expression of select cytochrome P450 (CYP) enzymes were also assessed in cryopreserved human hepatocytes. Further, the distribution and metabolism of 2-HOBA in blood were determined. Our results indicate that 2-HOBA is not cytotoxic or mutagenic in vitro and does not induce the expression of CYP1A2, CYP2B6, or CYP3A4 in human hepatocytes. The results of the hERG testing showed a low risk of cardiac QT wave prolongation. Plasma protein binding and red blood cell distribution characteristics indicate low protein binding and no preferential distribution into erythrocytes. The major metabolites identified were salicylic acid and the glycoside conjugate of 2-HOBA. Together, these findings support development of 2-HOBA as a nutritional supplement and provide important information for the design of further preclinical safety studies in animals as well as for human clinical trials with 2-HOBA.

Keywords: Human; Metabolism; Rabbit; Rat; Salicylamine; Toxicity.

MeSH terms

  • Adult
  • Benzylamines / pharmacology*
  • Blood Proteins
  • Cytochrome P-450 Enzyme System / metabolism
  • ERG1 Potassium Channel / genetics
  • ERG1 Potassium Channel / metabolism
  • Erythrocytes / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology
  • Humans
  • Male
  • Middle Aged
  • Mutagenicity Tests
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics


  • Benzylamines
  • Blood Proteins
  • ERG1 Potassium Channel
  • KCNH2 protein, human
  • Cytochrome P-450 Enzyme System
  • 2-(aminomethyl)phenol