Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations

BackgroundThe toxicity of herbal medicine combinations is critical to the clinical safety of traditional Chinese medicine (TCM). Current assessment methods are often inefficient and costly, creating an urgent need for new strategies to evaluate herbal medicine toxicity. We conducted research based o...

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Main Authors: Cheng Zhang, Yina Li, Fangyang Li, Wanyun Dang, Zhuo Shi, Chunqi Yang, Chengrong Xiao, Xianglin Tang, Yuguang Wang, Yue Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1590929/full
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author Cheng Zhang
Yina Li
Fangyang Li
Wanyun Dang
Zhuo Shi
Chunqi Yang
Chengrong Xiao
Xianglin Tang
Yuguang Wang
Yuguang Wang
Yuguang Wang
Yue Gao
Yue Gao
Yue Gao
Yue Gao
author_facet Cheng Zhang
Yina Li
Fangyang Li
Wanyun Dang
Zhuo Shi
Chunqi Yang
Chengrong Xiao
Xianglin Tang
Yuguang Wang
Yuguang Wang
Yuguang Wang
Yue Gao
Yue Gao
Yue Gao
Yue Gao
author_sort Cheng Zhang
collection DOAJ
description BackgroundThe toxicity of herbal medicine combinations is critical to the clinical safety of traditional Chinese medicine (TCM). Current assessment methods are often inefficient and costly, creating an urgent need for new strategies to evaluate herbal medicine toxicity. We conducted research based on the commonly used TCM, Psoraleae Fructus (PF), and its formulations, Er Shen Pills (ESP) and Si Shen Pills (SSP).MethodsWe conducted a series of analyses on Drosophila, including survival analysis, enzyme assays, and quantitative PCR(qPCR) tests, to evaluate the effects of various TCM combinations on fruit fly health and viability. Transcriptome sequencing was utilized to investigate the detoxifying mechanisms of these combinations. Additionally, experiments with Vibrio fischeri assessed toxicity changes by calculating the luminescence inhibition rate. An innovative similarity model was developed to identify toxic components within the TCM formulations. Finally, molecular docking and molecular dynamics simulations explored the mechanisms of action of these toxic components on Vibrio fischeri, providing a comprehensive understanding at the molecular level.ResultsIn Drosophila experiments, ESP and SSP groups showed longer survival times, with male flies being more sensitive, making them more suitable for toxicity studies. Enzyme assays indicated a decreasing toxicity trend for ESP and SSP compared to PF, with significant changes observed in female flies. The qPCR analysis revealed that the upregulation of cpr and cyp6a8, along with the downregulation of keap1, hsp22, hsp68, gstD6, and hsp83, can assess the toxicity changes of PF, ESP, and SSP. The primary detoxification pathway involves the metabolism of xenobiotics by cytochrome P450. In the Vibrio fischeri assay, the IC50(50% inhibition) value of ESP was the highest, indicating reduced toxicity compared to PF. Screening for toxic components revealed that PF had 4, ESP had 16, and SSP had 22 components, primarily acting on LuxD, LuxE, and LuxG enzymes.ConclusionA method for detecting the toxicity variation patterns of PF, ESP, and SSP can be established using Drosophila and Vibrio fischeri, and the mechanisms of toxic effects can be explored respectively through transcriptomics and virtual screening techniques.
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spelling doaj-art-a78390b4ffe24c008d0c9c4fc92bb4d32025-08-20T02:06:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15909291590929Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulationsCheng Zhang0Yina Li1Fangyang Li2Wanyun Dang3Zhuo Shi4Chunqi Yang5Chengrong Xiao6Xianglin Tang7Yuguang Wang8Yuguang Wang9Yuguang Wang10Yue Gao11Yue Gao12Yue Gao13Yue Gao14School of Pharmacy, Guangdong Pharmaceutical University, Guang zhou, ChinaSchool of Life Sciences, Hebei University, Baoding, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guang zhou, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guang zhou, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaFaculty of Environment and Life Science, Beijing University of Technology, Beijing, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaSchool of Life Sciences, Hebei University, Baoding, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaNational Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guang zhou, ChinaBeijing Institute of Radiation Medicine, Beijing, ChinaFaculty of Environment and Life Science, Beijing University of Technology, Beijing, ChinaNational Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, ChinaBackgroundThe toxicity of herbal medicine combinations is critical to the clinical safety of traditional Chinese medicine (TCM). Current assessment methods are often inefficient and costly, creating an urgent need for new strategies to evaluate herbal medicine toxicity. We conducted research based on the commonly used TCM, Psoraleae Fructus (PF), and its formulations, Er Shen Pills (ESP) and Si Shen Pills (SSP).MethodsWe conducted a series of analyses on Drosophila, including survival analysis, enzyme assays, and quantitative PCR(qPCR) tests, to evaluate the effects of various TCM combinations on fruit fly health and viability. Transcriptome sequencing was utilized to investigate the detoxifying mechanisms of these combinations. Additionally, experiments with Vibrio fischeri assessed toxicity changes by calculating the luminescence inhibition rate. An innovative similarity model was developed to identify toxic components within the TCM formulations. Finally, molecular docking and molecular dynamics simulations explored the mechanisms of action of these toxic components on Vibrio fischeri, providing a comprehensive understanding at the molecular level.ResultsIn Drosophila experiments, ESP and SSP groups showed longer survival times, with male flies being more sensitive, making them more suitable for toxicity studies. Enzyme assays indicated a decreasing toxicity trend for ESP and SSP compared to PF, with significant changes observed in female flies. The qPCR analysis revealed that the upregulation of cpr and cyp6a8, along with the downregulation of keap1, hsp22, hsp68, gstD6, and hsp83, can assess the toxicity changes of PF, ESP, and SSP. The primary detoxification pathway involves the metabolism of xenobiotics by cytochrome P450. In the Vibrio fischeri assay, the IC50(50% inhibition) value of ESP was the highest, indicating reduced toxicity compared to PF. Screening for toxic components revealed that PF had 4, ESP had 16, and SSP had 22 components, primarily acting on LuxD, LuxE, and LuxG enzymes.ConclusionA method for detecting the toxicity variation patterns of PF, ESP, and SSP can be established using Drosophila and Vibrio fischeri, and the mechanisms of toxic effects can be explored respectively through transcriptomics and virtual screening techniques.https://www.frontiersin.org/articles/10.3389/fphar.2025.1590929/fullpsoraleae fructusdetoxification in combination with TCMtoxicity detectingtoxic components screeningDrosophila melanogasterVibrio fischeri
spellingShingle Cheng Zhang
Yina Li
Fangyang Li
Wanyun Dang
Zhuo Shi
Chunqi Yang
Chengrong Xiao
Xianglin Tang
Yuguang Wang
Yuguang Wang
Yuguang Wang
Yue Gao
Yue Gao
Yue Gao
Yue Gao
Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
Frontiers in Pharmacology
psoraleae fructus
detoxification in combination with TCM
toxicity detecting
toxic components screening
Drosophila melanogaster
Vibrio fischeri
title Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
title_full Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
title_fullStr Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
title_full_unstemmed Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
title_short Integrating Drosophila and Vibrio fischeri models for toxicity evaluation: uncovering detoxification trends in psoralea Fructus-TCM formulations
title_sort integrating drosophila and vibrio fischeri models for toxicity evaluation uncovering detoxification trends in psoralea fructus tcm formulations
topic psoraleae fructus
detoxification in combination with TCM
toxicity detecting
toxic components screening
Drosophila melanogaster
Vibrio fischeri
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1590929/full
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