An Immune-Liver Microphysiological System Method for Evaluation of Hepatotoxicity Induced by Polygonum multiflorum Extract

Polygonum multiflorum Thunb. (PMT) has occasionally demonstrated adverse effects on liver function in clinical applications. These instances of hepatotoxicity have been linked to PMT samples. Due to its complex composition and mechanisms, evaluating the hepatotoxicity of PMT samples poses a significant challenge. Currently, it is known that three toxic components exhibit additive/synergistic effects, which further complicates the establishment of a toxicological quality control method. This study aimed to develop a biological evaluation method using a microphysiological system, termed i-LOC, which integrates hepatic and immune cells to mimic inflammatory cell infiltration. The i-LOC system demonstrated remarkable sensitivity in detecting both direct and inflammation-mediated hepatotoxic effects. Notably, the system significantly reduced the sample size requirements by four-thousand time compared to animal models. Additionally, i-LOC discovered the existence of unknown potentially hepatotoxic compounds in PMT, reinforcing the importance of establishing a comprehensive biological evaluation method for assessing PMT's hepatotoxicity. The successful implementation of the i-LOC method effectively evaluates PMT's hepatotoxicity, overcoming the challenges posed by its complexity.