Toxicological Evaluation of Lagerstroemia speciosa and Lagerstroemia tomentosa Extracts Using a Liver Organ-on-a-Chip System

Abstract The WHO guideline recommends that the potential toxicity of herbs be comprehensively examined in preclinical settings prior to clinical evaluation. Organ-on-a-chip (OOC) technology has been suggested for this purpose because of its capacity to reflect human responses. While Lagerstroemia speciosa extracts have been used as treatment of diabetes, Lagerstroemia tomentosa extracts have not been well studied; however, their hepatotoxicity is largely unknown. Thus, we assessed the hepatotoxicity of Lagerstroemia extracts using a human liver OOC with HepG2 cells and this system’s efficacy compared to its 2D counterpart. Lagerstroemia speciosa extracts were prepared from fresh (LS) or shed (LSS) leaves, and Lagerstroemia tomentosa extracts were prepared from fresh leaves (LT). The OOCs exposed to the extracts at low concentrations for 24 h exhibited minimal viability reductions and were more sensitive to the toxicity of LS and LSS than the 2D cultures. Albumin production, a hepatic functional marker, in the OOCs was impaired by LS and LT, even at low concentrations. Seven-day exposure of the OOCs to LS further reduced viability and albumin production. This OOC study revealed the potential hepatotoxicity of Lagerstroemia extracts, suggesting that functional assessments of the liver may be required during clinical studies involving these extracts.