An immune-liver microphysiological system method for evaluation and quality control of hepatotoxicity induced by Polygonum multiflorum thunb. Extract

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-04-09 Epub Date: 2025-03-13 DOI:10.1016/j.jep.2025.119633
Quanfeng Deng , Yueyang Qu , Yong Luo , Xiuli Zhang
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Abstract

Ethnopharmacological relevance

Clinical applications of Polygonum multiflorum Thunb. (PMT) have occasionally reported adverse effects on liver function, linking these instances of hepatotoxicity to PMT samples. Evaluating the hepatotoxicity of PMT, given its intricate composition and mechanisms, presents a notable challenge. Notably, three toxic components display additive/synergistic effects, further complicating the establishment of a toxicological quality control method.

Aim of the study

This study aims to develop a biology-based quality control method that can reflect the multi-mechanistic hepatotoxicity of PMT.

Materials and methods

We designed a microphysiological system tailored for the immune-liver interplay, termed the i-LOC, featuring three-cell channels. This i-LOC integrates hepatic cells with two distinct immune cell types to mimic inflammatory cell infiltration. As a control, a liver-on-chip devoid of immune cells was utilized to characterize hepatotoxicity induced by inflammatory stress.

Results

The i-LOC system exhibited remarkable sensitivity in detecting both direct and inflammation-mediated hepatotoxic effects of the three PMT toxic components. This system significantly reduced the sample size requirements by thousandfold compared to animal models, presenting a cost-effective and attractive alternative for PMT toxicological assessments. Intriguingly, the system identified the present of previously unknown PMT compounds with potential hepatotoxic properties, emphasizing the need for a comprehensive biological evaluation method.

Conclusion

This study successfully developed an i-LOC method for effectively evaluating PMT's hepatotoxicity, overcoming the complexities posed by its intricate composition and mechanisms.

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何首乌肝毒性的免疫-肝脏微生理系统评价与质量控制。提取。
民族药理学相关性:何首乌的临床应用。(PMT)偶尔报告对肝功能的不良影响,将这些肝毒性实例与PMT样品联系起来。鉴于其复杂的成分和机制,评估PMT的肝毒性是一个显着的挑战。值得注意的是,三种有毒成分表现出加性/协同效应,进一步复杂化了毒理学质量控制方法的建立。研究目的:本研究旨在建立一种能够反映PMT多机制肝毒性的生物学质量控制方法。材料和方法:我们设计了一种针对免疫-肝脏相互作用量身定制的微生理系统,称为i-LOC,具有三细胞通道。这种i-LOC将肝细胞与两种不同的免疫细胞类型结合起来,模拟炎症细胞浸润。作为对照,缺乏免疫细胞的肝脏芯片被用来表征炎症应激诱导的肝毒性。结果:i-LOC系统在检测三种PMT毒性成分的直接和炎症介导的肝毒性作用方面表现出显著的敏感性。与动物模型相比,该系统显着减少了数千倍的样本量要求,为PMT毒理学评估提供了一种具有成本效益和吸引力的替代方案。有趣的是,该系统发现了以前未知的具有潜在肝毒性的PMT化合物,强调需要一种全面的生物学评估方法。结论:本研究成功建立了一种有效评估PMT肝毒性的i-LOC方法,克服了其复杂的成分和机制所带来的复杂性。
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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
期刊介绍: The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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