JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Sheng-Ya Guo,Yong Zhang,Xing-Hui Chen,Yi-Wen Zhang,Bing-Bing Cao,Shi-Chang Zhu,Dao-Zong Xia
Ethnopharmacological relevance Smilax glabra Roxb. (taxonomically verified via http://www.theplantlist.org , accessed December 17, 2025), commonly known as “Tu fuling” in China, is a well-recognized traditional Chinese herb extensively used for detoxification, dampness relief, and diuresis. Our previous research has demonstrated that Smilax glabra flavonoids extract (SGF) alleviate lead (Pb)-induced renal damage. However, the protective effects of SGF against Pb-induced neurotoxicity and hematotoxicity remain largely uninvestigated, and the underlying molecular mechanisms have not been fully elucidated. Aim of the study To reveal the potential protective effects and underlying molecular mechanisms of SGF against Pb-induced neurotoxicity and hematotoxicity, a lead poisoned zebrafish model was utilized. Materials and methods Zebrafish were randomly divided into four groups: (a) control group (no treatment); (b) Pb group (exposed to 80 μM lead acetate); (c) positive control group (Pb + DMSA group: first exposed to 80 μM lead acetate, then separately exposed to 15.6 μg/mL DMSA); (d) Pb + SGF groups (first exposed to 80 μM lead acetate, then separately exposed to SGF at 31.2, 62.5, or 125 μg/mL). All zebrafish were subjected to the respective sequential treatments for 4 consecutive days. Results Our results showed that SGF significantly reduced Pb content in zebrafish. SGF treatment markedly alleviated a series of adverse effects induced by Pb exposure in zebrafish, including trunk curvature, shortened body length, peripheral motor neuron damage, myelin and axonal injury, neuronal apoptosis, neurobehavioral impairment, and anemia. Moreover, SGF treatment led to a significant decrease in ROS levels in Pb-exposed zebrafish. Mechanistic experiments demonstrated that SGF significantly upregulated the mRNA expression levels of nerve protection-related genes ( shha , gfap , mbp , and huc ), memory-related genes ( ache and gdnf ), and antioxidant-related genes ( nrf2 and cat ). Conversely, SGF predominantly downregulated the mRNA expression levels of inflammation-related genes ( il1β , il6 , and tnfα ) and apoptosis-related genes ( caspase 3 , bax , and p53 ). Meanwhile, SGF treatment significantly reduced the phospho-p65/p65 protein ratio. Conclusion These results suggest that SGF may mitigate acute Pb-induced neurotoxicity and hematotoxicity, and these protective effects are associated with enhanced Pb excretion and the inhibition of Pb-induced oxidative stress, inflammation, and apoptosis. Moreover, the neuroprotective and memory-improving effects of SGF were observed in conjunction with the regulation of neurotrophic factors. Our findings highlight the potential pharmacological value of SGF in counteracting lead poisoning. However, given that the acute high-dose model does not fully recapitulate chronic low-dose human exposure, further validation in chronic models is essential before translational conclusions can be drawn.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Zhuoshuo Zhou,Weirong Sun,Liye Yang,Yue Li,Hongpeng Guo,Ximing Cui,Yanli Zhao,Jinlian Li,Gang Wang,Dongmei Wu
Ethnopharmacological relevance Physalis alkekengi L. ( P. alkekengi ) is widely used in traditional medicine and functional foods for its various medicinal properties. However, its toxicological profile has not been comprehensively assessed. Aim of the study This study aimed to characterize the developmental toxicity and cardiotoxicity of P. alkekengi using a Danio rerio ( D. rerio ) embryo model and to identify key toxic constituents to support safety optimization. Materials and methods D. rerio embryos were exposed to the fruit and calyx extracts of P. alkekengi as well as membrane-fractionated preparations to assess toxic phenotypes. Chemical profiling was performed using ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-Exactive Orbitrap-MS), and mechanistic insights were explored using apoptosis-related assays and network toxicology analysis. Results The fruit extract of P. alkekengi exhibited stronger developmental toxicity and cardiotoxicity effects compared to the calyx extract. The 5–10 kDa non-polysaccharide fraction of the fruit was identified as the primary toxic source, with Glycidyl stearate (GS) being the key cardiotoxic component in this fraction. Removal of the most toxic 5–10 kDa fraction during the extraction process significantly reduced the toxicity of the fruit extract. Conclusion The toxicity of P. alkekengi fruit extract is concentrated in the non-polysaccharide 5–10 kDa fraction, with GS being the main contributor to the toxicity in this fraction. Membrane-based separation technology to remove this fraction can enhance the safety of the extract. This study provides a framework for the safety evaluation and optimization of traditional medicinal plants.
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ENVIRONMENTAL POLLUTION
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2022
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IF 9.988
Yinxuan Lin,Jiao Yu,Meng Wang,Lingling Wu
The combined pollution of antibiotics and heavy metals has attracted a worldwide attention in the recent years. 4-epianhydrotetracycline (EATC) is the major degradation product of tetracycline (TC), which has been detected frequently in environment and its concentration is even higher than TC under some circumstances. Cadmium (Cd) is a common heavy metal contaminant and has highly toxic to organisms, plants and humans even at low doses. In the present study, zebrafish ( Danio rerio ) embryo toxicity test was performed to investigate the single and combined effects of EATC and Cd on aquatic organisms. Exposure to EATC and Cd at environmentally relevant concentrations had a series of hazardous impacts on the embryonic development , including lethality , hatching rate, heart rate and teratogenic effects . Compared to the contaminant existed alone, combined pollution produced stronger toxicity, which appeared as the decreasing of heart rate and hatching rate, and the increasing of malformation of zebrafish embryos. After 96 h exposure, the reactive oxygen species (ROS) levels in zebrafish embryos were increased significantly, revealing that EATC-Cd co-exposure resulted in potential oxidative stress-induced damage. Acridine orange (AO) staining showed that combined exposure resulted in stronger cell apoptosis. The potential health risks of the combined pollution of EATC and Cd should be paid more attention to higher level vertebrates and humans.
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JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Hongdan Wang,Yunqing Wang,Qiaoning Wang,Min Lv,Xizhen Zhao,Yunxia Ji,Xiaoyue Han,Xiaoyan Wang,Lingxin Chen
Microplastics (MPs) have the characteristics of large specific surface area, high hydrophobicity and surface charge, so they are easy to combine with other pollutants and cause toxic effects on aquatic organisms. Here, we prepared a polyvinyl chloride-microplastics (PVC-MPs) fragmentation model to simulate the real microplastic state, and characterized its composition, morphology, particle size and zeta potential . On this basis, we used single and compound exposure of PVC and di(2-ethylhexyl) phthalate (DEHP) to explore their effects on hatchability and mortality of zebrafish ( Danio rerio ) embryos and toxicity to oxidative stress and cardiac development in zebrafish larvae. Herein, PVC-MPs slowed down the hatching rate of zebrafish embryos and induced the death of zebrafish, while DEHP could slow down the induced of death, it had no effect on hatching rate. The PVC-MPs/DEHP single pollution could induce the reactive oxygen species (ROS) and activated the antioxidant defense signaling pathway, while the compound group showed the level of feedback autoregulation of NF-E2-related factor 2 (Nrf2) signaling pathway. The single pollution also could inhibit the expression of genes related to cardiac development, while the combined pollution showed an antagonistic effect. This study provided a theoretical basis for the ecotoxicology and biomonitoring of MPs in the natural state.
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Life-Basel
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2022
·Vol. 12
·期 1
·128
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IF 3.251
Davide Di Paola,Sabrina Natale,Enrico Gugliandolo,Marika Cordaro,Rosalia Crupi,Rosalba Siracusa,Ramona D’Amico,Roberta Fusco,Daniela Impellizzeri,Salvatore Cuzzocrea,Nunziacarla Spanò,Fabio Marino,Alessio Filippo Peritore
Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then the anti-inflammatory action of PEAOXA was evaluated for the first time in the zebrafish model (Danio rerio). Different concentrations of PEAOXA were tested for toxicity on zebrafish embryonic development; only the highest concentration of 30 mg/L showed toxic effects. Quantitative RT-PCR was applied to detect Tumor necrosis factor-α, Interleukin 1β, 6, and 8, and members of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Exposure to LPS induced an increase in pro-inflammatory cytokines (tumor necrosis factor and interleukin 1, 6, and 8) in both gene and protein expression, as well as an increase of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the nuclear factor kappa light polypeptide enhancer in B-cells inhibitor (IκBα) gene expression. Furthermore, acute LPS exposure also induced an increase in tryptase release, related to mast cell activity, and in the production of apoptosis-related proteins (caspase 3, bax, and bcl-2). Treatment with PEAOXA 10 mg/L significantly counteracts LPS-induced inflammation in terms of cytokine expression and decreases tryptase release and the apoptosis pathway.Keywords:zebrafish;inflammation;PEAOXA;cytokines;apoptosis
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CHEMOSPHERE
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2023
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IF 8.8
Nan Zhou,Huihui Liu,Xianhai Yang,Peter Watson,Feifei Yang
The COVID-19 pandemic resulted in increasing the usage of iodinated contrast media (ICM), and thus an increase in the prevalence of ICM-contaminated wastewater. While ICM is generally safe, this has the potential to be problematic because as medical wastewater is treated and disinfected, various ICM-derived disinfection byproducts (DBPs) may be generated and released into the environment. However, little information was available about whether ICM-derived DBPs are toxic to aquatic organisms. In this study, the degradation of three typical ICM (iopamidol, iohexol, diatrizoate) at initial concentration of 10 μM and 100 μM in chlorination and peracetic acid without or with NH 4 + was investigated, and the potential acute toxicity of treated disinfected water containing potential ICM-derived DBPs on Daphnia magna , Scenedesmus sp. and Danio rerio was tested. The degradation results suggested that only iopamidol was significantly degraded (level of degradation >98%) by chlorination, and the degradation rate of iohexol and diatrizoate were significantly increased in chlorination with NH 4 + . All three ICM were not degraded in peracetic acid. The toxicity analysis results indicate that only the disinfected water of iopamidol and iohexol by chlorination with NH 4 + were toxic to at least one aquatic organism. These results highlighted that the potential ecological risk of ICM-contained medical wastewater by chlorination with NH 4 + should not be neglected, and peracetic acid may be an environment-friendly alternative for the disinfection of wastewater containing ICM.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Qian Wang,Xianxu Li,Xiangfeng Yao,Jia Ding,Juan Zhang,Zhuran Hu,Jinhua Wang,Lusheng Zhu,Jun Wang
Butyl benzyl phthalate (BBP), a widely used class of plasticizers , has caused considerable concerns due to its widespread detection in various environmental media. However, the potential impact of BBP on the brain and its underlying molecular mechanisms remain poorly understood. In this study, adult zebrafish ( Danio rerio ) were exposed to 0, 5, 50, and 500 μg/L BBP for 28 days. Elevated levels of both reactive oxygen species and 8-hydroxydeoxyguanosine were observed, indicating the occurrence of oxidative stress and DNA damage. Furthermore, exposure to BBP resulted in neurotoxicity, apoptosis, and histopathological damage within the zebrafish brain. Transcriptome analysis further revealed that Gene Ontology terms associated with muscle contraction were specifically expressed in the brain after BBP exposure. In addition, BBP altered the transcriptome profile of the brain, with 293 genes induced and 511 genes repressed. Kyoto Encyclopedia of Genes and Genomes analysis highlighted the adverse effects of BBP on the complement and coagulation cascades and two cardiomyopathy-related pathways. Taken together, our results revealed that BBP resulted in brain oxidative stress, histological damage, and transcriptome alterations. These findings have the potential to offer novel insights into the adverse outcome pathways of key events in the brain.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Xing Liu,Mingzhu Xia,Xinyi Wu,Ruobing Chen,Yuting Peng,Yi Fan,Junjie Han,Yichun Zhao,Man Qu
Perfluorooctanoic acid (PFOA), a pervasive environmental contaminant, is implicated in ocular diseases through prenatal/embryonic exposure. This study investigated the protective effects of nomilin, a citrus-derived bioactive compound with therapeutic properties, against PFOA-induced ocular and visual impairments in zebrafish. Integrating network toxicology and molecular docking, we identified seven shared targets (including PIK3CA and mTOR) linking PFOA, nomilin, and ocular diseases. Experimental results demonstrated that PFOA exposure suppressed the PIK3CA/AKT/mTOR/pax6 axis, significantly downregulated (by approximately 0.23- to 0.65-fold) ocular development genes (rx1, vsx1, rpgra, lhx4), and induced structural defects (reduced eye size, lens diameter and retinal layer thickness) and visual dysfunction. Nomilin treatment dose-dependently reversed these effects by activating the PIK3CA/AKT/mTOR/pax6 axis, restoring the expression of ocular developmental related genes by 1.45- to 2.85-fold compared to the PFOA-exposed group, improving ocular morphology, and enhancing visual response behaviors. Furthermore, nomilin attenuated PFOA-induced apoptosis. These findings reveal that nomilin mitigates PFOA-mediated ocular toxicity via PIK3CA activation, offering novel therapeutic insights for environmental pollutant-related ocular disorders.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
·
IF 7.129
Shuhui Zhang,Zhenhua Fu,Yixin Xu,Xin Zhao,Mingzhu Sun,Xizeng Feng
In vertebrates, the behavior of congenital sex differences between males and females is highly dependent on steroid signals and hormonal milieu. The presence of endocrine disrupting chemicals (EDCs) in the environment generally plays a similar role to sex hormones, so its interference with aquatic organism population stability can not be ignored and is worth studying. Fluorene-9-bisphenol (BHPF) has been clarified as an endocrine disruptor on organisms by several studies but its mechanism in perturbation of courtship behavior of female zebrafish is not clear. Here, we proposed an automated multi-zebrafish tracking method quantifying the courtship process and reported that zebrafish females exposed to BHPF, are not receptive to males but rather court females, and lose normal ovarian function with an altered sex steroid milieu. Our results showed that BHPF damaged 17β-estradiol synthesis by down-regulation of sox3 and cyp19a1a , linking apoptosis with ovary development and female fecundity. The down-regulated expression of estrogen signaling through an estrogen receptor, esr2b , caused the induction of masculinization of female courtship behavior and sexual preference in zebrafish females after BHPF treatment. This process might be mediated by inhibiting the transcription of a neuropeptide B ( npb) in the brain. Our study reveals that the estrogen signaling pathway may play an important role in classical courtship behavior and sexual preference of zebrafish. This study provided evidence that anti-estrogenic chemical exposure caused adverse effects on the regulation of the brain-gonad-estrogen axis of aquatic organisms, which should be of concern and highlighted the importance of controlling environmental contamination.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Hongpeng Guo,Shuhong Liu,Yue Li,Zhuoshuo Zhou,Xiaoyan Yu,Naitian Zhang,Zhong Wang,Jinlian Li,Tianwei Dong,Dongmei Wu
Ethnopharmacological relevance Rhododendron dauricum L. is used in traditional medicine for respiratory disorders, but its developmental and cardiac safety remains insufficiently defined. Aim of the study To characterize developmental/cardiac phenotypes induced by Rhododendron dauricum hot-water extract (RDWE), identify toxicity-enriched fractions and candidate constituents, and assess whether selective fraction removal reduces toxicity-related effects. Materials and methods Zebrafish embryos/larvae were exposed to RDWE, four membrane fractions, and candidate monomers. LC50 values were calculated from 96 hpf mortality data using three replicate wells per concentration and 10 embryos per well. Candidate monomers were tested over 0-200 mg/L; rhododendrol-associated responses were examined at 0-40 mg/L using RNA-seq, Fluo-4, ROS, AO staining, and qRT-PCR. Results RDWE induced concentration-dependent developmental/cardiac abnormalities, mainly pericardial and yolk-sac edema, with a 96 hpf LC50 of 228.5 mg/L (95% CI, 181.8-276.2). The 5-10 kDa fraction showed the highest mortality-based potency among fractions (80.68 mg/L; 95% CI, 66.70-94.97). Rhododendrol showed the lowest LC50 among candidate monomers (67.82 mg/L; 95% CI, 55.65-81.49) and induced pericardial edema and bradycardia. Rhododendrol-associated cardiotoxicity was accompanied by calcium accumulation, oxidative stress, apoptosis-related signals, calcium-signaling enrichment, down-regulation of cacna1ab, cacna1da, atp2a1l, and cat, and up-regulation of cu/zn-sod and caspase3/8/9. Removing the 5-10 kDa fraction increased the LC50 to 321.0 mg/L (95% CI, 299.0-347.9). Conclusions The 5-10 kDa fraction was identified as a toxicity-enriched fraction, and rhododendrol was identified as a potential key contributor to toxicity. Selective removal of this fraction may represent a potential toxicity-reduction strategy, but further validation is required to determine whether pharmacological activity, chemical consistency, and mammalian relevance are retained after fraction removal.
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ACS ES&T Water
·
2025
·
IF 4.3
Yaru Zhang,Jingna Cui,Shouchun Xiao,Xueke Liu,Li Zheng,Peng Wang,Donghui Liu,Fanrong Zhao
The frequent occurrence of pesticides and nanoparticles in aquatic environments raises ecological concerns. Tebuconazole (TEB) is a widely used triazole fungicide, and zinc oxide nanoparticles (ZnO NPs) are one of the commonly used engineered nanoparticles. Both are frequently detected in the aquatic environment, yet their combined effects on aquatic organisms remain inadequately understood. In this study, we investigated the impacts of coexposure to environmentally relevant concentrations of ZnO NPs on the toxicity and bioaccumulation of TEB in zebrafish (Danio rerio). The 96-h median lethal concentration (LC50) of TEB to zebrafish was 6.45 mg/L. Coexposure to ZnO NPs (1–100 mg/L) led to a slight increase in acute toxicity of TEB. Long-term (28-day) coexposure to environmentally relevant concentrations of TEB and ZnO NPs exacerbated oxidative stress and apoptosis, decreased the activity of the detoxification enzyme carboxylesterase, and upregulated cytochrome P450 activity. Additionally, ZnO NPs did not enhance the accumulation of TEB but prolonged its clearance and altered its bioaccumulation pattern. These results indicate that the presence of ZnO NPs may increase the potential risk associated with TEB exposure in zebrafish, underscoring the need for further investigation of the interactive effects of pesticides and engineered nanomaterials in aquatic ecosystems.
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ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Aiping Wang,Yue Sun,Zhengyi Sun,Xiao Liu,Xin Yu,Ke Li,Xianxia Zhang,Yue Xu,Wei Mu,Beixing Li
The behavior of pesticide particles or droplets might significantly influence their environmental risks. However, studies on the risk of different pesticide formulations in aqueous environments have rarely been reported. In this study, we prepared three types of pyraclostrobin formulations to evaluate their behavior in the aqueous environment and toxicological risks to zebrafish. The results showed that pyraclostrobin emulsifiable concentrate (EC) sank faster in water with increasing hydrophilicity and density of the solvent. The particles also sank faster with increasing particle size and particle density for suspension concentrate (SC) and microcapsules (MCs). Diverse behavior in water results in different temporal and spatial distributions of the active ingredient. EC-EGDA, SC-5 μm, CS-Large and EC-MO sink or float over time, therefore reducing the effective dose suspended in water. Lower toxicological risks of the pesticides were also observed by reducing the enrichment of pyraclostrobin in zebrafish. In addition to the direct toxicity of the active ingredient, the type of pesticide formulations and their specific compositions might also influence the integrated toxicity. The environmental behavior of pesticide formulations should also be considered for their systematic assessment of environmental risks to ensure the scientific application of pesticides in different scenarios.
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危险品化学品经营许可证（带存储）