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.

Polygonum multiflorum Thunb.（何首乌）在临床应用中偶有对肝脏功能产生不良影响的记录。此类肝毒性反应与何首乌样品相关联。鉴于其复杂的成分及作用机制，评估何首乌样品的肝毒性构成一项重大挑战。目前已知三种有毒成分表现出叠加/协同效应，这进一步增加了建立毒理学质量控制方法的复杂性。本研究旨在开发一种基于微生理系统的生物评价方法，称为i-LOC系统，该系统整合肝细胞和免疫细胞以模拟炎症细胞浸润。i-LOC系统在检测直接和炎症介导的肝毒性效应方面表现出卓越的敏感性。值得注意的是，与动物模型相比，i-LOC系统显著降低了样本量需求，降低了四千倍。此外，i-LOC系统发现了何首乌中存在未知的有潜在肝毒性化合物，进一步强调了建立全面生物评价方法以评估何首乌肝毒性的重要性。i-LOC方法的成功实施有效地评估了何首乌的肝毒性，克服了其复杂性带来的挑战。