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Updated: Dec 16, 2025
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
[Study on potential hepatotoxicity of main monomers of Polygonum multiflorum based on liver micro-tissue]
Qi Wang1, Qian-Hui Zhang2, Hai-Ruo Wen1
1National Institutes for Food and Drug Control Beijing 100050, China.
Abstract:
In this study, we aimed to establish a rat liver micro-tissue evaluation system to evaluate the hepatotoxicity of the main monomers in Polygonum multiflorum. Rat primary hepatocytes were isolated and purified by two-step in situ perfusion method to prepare hepatic parenchymal cells. The ultra-low adsorption plate and the inverted model were used to establish an in vitro hepatotoxicity evaluation system. After the system was established, the main monomer components(monanthone with emodin type, rhein, emodin, emodin-8-O-β-D-glucopyranoside, physcion) of P. multiflorum were selected for in vitro hepatotoxicity evaluation. This study showed that the primary cells of the liver can form liver micro-tissues in the low adsorption plate method and the mold perfusion method, with good liver structure and function, which can be used to evaluate the hepatotoxicity of the drug to be tested after long-term administration. The five monomers to be tested in P. multiflorum can significantly affect the proliferation of primary liver micro-tissues in rats in a dose-and time-dependent manner. The hepatotoxic effects were as follows: monanthone with emodin type > rhein > emodin > emodin-8-O-β-D-glucopyranoside > physcion. The results suggested that the emodin-type monoterpene and rhein might be the potential hepatotoxic components, while the metabolites of emodin-8-O-β-D-glucoside and emodin methyl ether showed more toxic risks. The rat primary hepatocyte micro-tissue model system established in this experiment could be used to achieve long-term drug administration in vitro, which was consistent with the clinical features of liver injury caused by long-term use of P. multiflorum. The experimental results provided important information and reference on the clinical application and toxic component of P. multiflorum.
Insights
This study developed a rat liver micro-tissue model to assess Polygonum multiflorum
Area of Science:
- Hepatotoxicity assessment
- Drug-induced liver injury
- Traditional Chinese Medicine research
Background:
- Polygonum multiflorum (P. multiflorum) is a traditional Chinese medicine.
- Concerns exist regarding its potential hepatotoxicity with long-term use.
- Identifying specific toxic components is crucial for safe clinical application.
Purpose of the Study:
- To establish a robust in vitro rat liver micro-tissue system.
- To evaluate the hepatotoxicity of key P. multiflorum monomers.
- To correlate in vitro findings with clinical observations of liver injury.
Main Methods:
- Isolated and purified rat primary hepatocytes using a two-step in situ perfusion method.
- Established an in vitro hepatotoxicity evaluation system using ultra-low adsorption plates and an inverted model.
- Assessed the effects of five P. multiflorum monomers on primary liver micro-tissues.
Main Results:
- Rat primary hepatocytes formed functional liver micro-tissues suitable for long-term administration studies.
- Five P. multiflorum monomers exhibited dose- and time-dependent effects on micro-tissue proliferation.
- Hepatotoxicity ranking: monanthone (emodin type) > rhein > emodin > emodin-8-O-β-D-glucopyranoside > physcion.
Conclusions:
- The established rat primary hepatocyte micro-tissue model accurately reflects long-term drug administration effects.
- Emodin-type monoterpenes and rhein are potential hepatotoxic components of P. multiflorum.
- The study provides critical insights into P. multiflorum's clinical safety and toxicological profile.
