Biomed Research International
·
2015
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IF 1.579
Wen-Hao Yu,Na Zhang,Jin-Feng Qi,Chen Sun,Yong-Hui Wang,Mei Lin
Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice () were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (), PAH accumulations in the kidney tissues were significantly higher (), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).
研究领域:
药理学
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毒理学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
·
2025
·
IF 5.8
Gu Yuang,Yao Yu,Lou Qiuwen,Zhu Xinyan,Lan Ju,Gao Chenshu,Wu Shuangshuang,Liang Jingjia,Xu Cenglin,Wang Yi,Cheng Heming,Chen Zhong
Epilepsy is one of the most prevalent and severe neurological disorders, and it is inadequately controlled with currently available medications. While cinnabar (mercury(II) sulfide)—a traditional Chinese medicine—has historical application in epilepsy treatment, its therapeutic efficacy and underlying mechanisms are unclear. In this study, we find that cinnabar exerts model-dependent antiseizure efficacy in mice. Specifically, it significantly attenuates acute seizures, enhances the termination of diazepam-resistant status epilepticus, and reduces spontaneous seizures in the kainic acid (KA)-induced seizure model. Conversely, no therapeutic effect was found in the maximal electroshock-, pentylenetetrazole-, or kindling-induced seizure model. Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity and γ-aminobutyric acid hypoactivity. Furthermore, cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors, while showing no alterations in motor function. Our findings suggest cinnabar's potential as a therapeutic agent for seizure management, via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.
研究领域:
神经病学
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药理学
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分子神经科学
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转化医学
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药物毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2011
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IF 2.466
Xinrui Zhou,Liming Wang,Xinming Sun,Xiuwei Yang,Chunying Chen,Qi Wang,Xiaoda Yang
Ethnopharmacological relevance Cinnabar (Cin), a naturally occurring mercuric sulfide (HgS), is a mineral widely used in traditional Chinese medicine throughout history. As for the toxicity of cinnabar, one important assumption is that cinnabar may be transformed into highly toxic methylmercury by gastrointestinal flora . There is no evidence in humans to support this assumption. Aim of the study To investigate the biotransformation of cinnabar (HgS) in the human intestinal bacteria with modern analytical techniques. Materials and methods A gas chromatograph, equipped with electron capture detection (GC-ECD) and mass spectrometry (GC–MS), were used to detect the formation of methylmercury after incubation of cinnabar with human intestinal bacteria. The content of soluble mercury in the bacteria media was determined by cold vapor-atomic absorption spectrometry (CV-AAS). In addition, X-ray absorption near-edge structure spectroscopy (XANES) was used to confirm the possible transformation of cinnabar in the bacteria media, and under mimetic intestinal condition by measuring the species of sulfur and mercury in the reaction extraction of cinnabar and Na 2 S mixture. Results No methylmercury was detected by both GC-ECD and GC–MS, which suggest that cinnabar (HgS) is not methylated in the human intestine. A small amount of soluble mercury was found to be released in the flora medium of HgS or cinnabar by CV-AAS. The XANES analyses revealed that polysulfides exist in the flora medium, and the simulated results showed that the products by incubating cinnabar with Na 2 S were mercuric polysulfides. Conclusion These results showed that under gut flora conditions cinnabar would be transformed into mercuric polysulfides rather than methylmercury. Our work provides evidences of nontoxic transformation of cinnabar in the human intestinal bacteria.
研究领域:
药理学
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环境医学
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毒理学
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DOI
高影响因子
Frontiers in Endocrinology
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2025
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IF 4.6
Yifan Zhang,Qingsong Qu,Ertong Dai,Ruiyan Liu,Bilin Jin,Zixuan Lu,Hui Kong,Yue Zhang,Huihua Qu,Yan Zhao
Background Glucose metabolism plays a central role in maintaining systemic energy homeostasis, and its dysregulation is closely linked to the pathogenesis of metabolic diseases such as diabetes mellitus. While traditional mineral medicines such as realgar and cinnabar have a long history of use, their roles in glycometabolism remain poorly defined. Methods Male C57BL/6J mice were used to establish both normoglycemic and streptozotocin (STZ)-induced diabetic models. Oral glucose, starch, protein, fat, and cellulose load tests were performed to evaluate the effects of realgar and cinnabar on postprandial glycemia and thermoregulation. Random blood glucose, body temperature, and insulin levels were monitored. α-Glucosidase and α-amylase inhibition assays were conducted in vitro to explore potential digestive enzyme-targeted mechanisms. Results Realgar and cinnabar significantly reduced blood glucose levels in diabetic mice and attenuated postprandial glycemic excursions in normal mice following oral glucose and starch loading. Further analysis revealed elevated insulin levels and dose-dependent inhibition of α-glucosidase and α-amylase activities. However, these hypoglycemic effects were abolished when glucose was administered intraperitoneally, and no significant changes in blood glucose were observed under non-carbohydrate nutrient loads (fat, protein, or fiber). Conclusion This study provides the first systematic evidence that realgar and cinnabar exert hypoglycemic effects, which involving enhanced insulin secretion and inhibition of key digestive enzymes. Their substrate-specific actions and partial influence on thermoregulation suggest broader roles in metabolic regulation and warrant further investigation in chronic models and energy homeostasis pathways.
研究领域:
药理学
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内分泌学
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代谢性疾病
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传统医学
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营养代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2025
·
IF 3.3
Ziyan Han,Yuzhou Zhuo,Zhihui Dai,Xinhui Zhang,Bingqian Zhu,Yuyan Liu,Zhuoyu Chai,Jiayi Wu,Lijun Chen
Background Cinnabar is a mercury-containing mineral traditionally used in Chinese medicine and can induce kidney injury via mercury toxicity. Given that cinnabar contains elements such as selenium, it is reasonable to hypothesize that its multi-element composition may regulate nephrotoxicity through intermetallic interactions. To validate this hypothesis and clarify the distinct renal toxicity between cinnabar and single mercury compounds, we compared the nephrotoxic effects of cinnabar, Zhu-Sha-An-Shen-Wan (ZSASW), mercuric sulfide (HgS), and mercuric nitrate (Hg(NO₃)₂). By co-administration with sodium selenite (Na₂SeO₃), this study related to the nephrotoxicity of cinnabar was improved from the perspective of metal-element interactions, which provided a new perspective for the safety assessment of mercury-containing medicines. Methods Mice were gavaged with 0.5 % CMC-Na solution, cinnabar (50.0 and 200 mg/kg), HgS (50.0 mg/kg), Na 2 SeO 3 (1.00 mg/kg), cinnabar (50.0 mg/kg)+Na 2 SeO 3 (1.00 mg/kg), HgS (50.0 mg/kg)+Na 2 SeO 3 (1.00 mg/kg), ZSASW (600 mg/kg), ZSASW (600 mg/kg)+Na 2 SeO 3 (1.00 mg/kg) or Hg(NO 3 ) 2 (0.900 mg/kg in Hg 2+ ) daily for 30 days. Renal histopathology was assessed by H&E staining. Related protein expression was measured by Western blotting. Renal total Hg (THg) concentration in kidney was determined by cold vapor atomic fluorescence spectroscopy. Result Western blotting revealed significantly decreased OAT1 and GPX4 levels in all experimental groups compared to the Control group ( P < 0.05). NF-κB activation occurred in the Hg(NO₃)₂, Cinnabar-H, HgS, and HgS-Na₂SeO₃ groups. Hg(NO₃)₂ administration caused a significant decline in body weight growth rate ( P < 0.001), severe renal tubular degeneration with epithelial cell swelling, and the highest renal THg concentration (773.77 % exceeding the Control group). Na₂SeO₃ alone induced inflammatory infiltration and tubular epithelial degeneration. The Cinnabar-H and HgS groups exhibited distinct renal damage (localized tubular degeneration and vascular hyaline degeneration, respectively) with elevated renal THg concentration (330.74 % and 347.95 % exceeding the Control group). The Cinnabar-L, Cinnabar-Na₂SeO₃, ZSASW, and ZSASW-Na₂SeO₃ groups maintained normal histology despite increased renal mercury content (227.46 %, 40.57 %, 67.2 %, and 556.56 % exceeding the Control group). Co-administration of Na₂SeO₃ with HgS restored OAT1 and GPX4 expression ( P < 0.001), suppressed NF-κB activation, and minimally altered renal mercury accumulation (RSD=0.45 %). Na₂SeO₃ reduced mercury levels in the cinnabar-treated mice (57.07 % reduction) but increased accumulation in ZSASW-treated mice (292.65 % increase). Conclusion This study confirms that cinnabar and ZSASW exhibit lower toxicity than mercuric sulfide or mercuric nitrate. Multi-component synergistic or antagonistic effects need to be considered when studying the mechanism of action of cinnabar-related drugs.
研究领域:
毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
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IF 5.2
Kai Hu,Wuliji Hasi,Guoqiang Fang,Siqingaowa Han
Cinnabar, with low water solubility and poor oral absorption, poses challenges in toxicity assessment. Relying solely on total mercury leads to overestimation, making detection of soluble Hg 2+ essential. This study presents a surface-enhanced Raman scattering (SERS) strategy using Au concave nanocubes (Au CNC) modified with 3-mercaptopropionic acid (3-MPA) and 4-mercaptopyridine (4-MPY), combined with a data-augmented convolutional neural network-partial least squares regression (CNN-PLS) model, for quantifying soluble Hg 2+ in cinnabar and its preparations. 3-MPA binds Hg 2+ , inducing Au CNC aggregation and enhances the SERS signal, while 4-MPY improves sensitivity. To overcome insufficient data in practical, data augmentation was used to expand the SERS dataset, and the performance of CNN, PLS, and CNN-PLS models was compared before and after augmentation. The results indicate that the data-augmented CNN-PLS model performed best, with a coefficient of determination (R 2 ) of 0.999 in the range of 0.001–1 μg/mL and a Mean Squared Error of Prediction (MSEP) of 0.0001. This method was applied to quantify Hg 2+ leaching from cinnabar and four cinnabar-containing preparations after 12 h of immersion in artificial gastric juice. The mean Hg 2+ concentrations from three cinnabar batches were 0.691, 0.557, and 0.546 μg/mL, while for the preparations, the concentrations were 0.085, 0.047, 0.038, and 0.023 μg/mL. These results showed excellent agreement with atomic fluorescence spectrometry (AFS), confirming the method's reliability and accuracy. This simple, accurate, and safe approach offers a novel solution for mercury safety assessment in cinnabar and its preparations, with significant potential for traditional Chinese medicine safety evaluation and environmental monitoring.
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
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IF 2.63
Songsong Wang,Xiao Xiao,Ao Li,Peng Li
An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH’s herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH’s herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.
研究领域:
药理学
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毒理学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2022
·Vol. 18
·期 2
·193-198
·
IF 0.743
Xu Bo-Yang,Zhu Si-Qi,Cheng Xian-Xin,Xu Yu,Liu Ji-Wu
Background: Compound Niuhuang Xiaoyan capsule is a realgar and cinnabar-containing traditional Chinese medicine, the contents of total arsenic and total mercury are found over regulation defined limits. However, only small amounts of arsenic in realgar and mercury in cinnabar are dissolved
in the gastric juice, so the determination of soluble arsenic and soluble mercury is more significant than that of total arsenic and total mercury in Compound Niuhuang Xiaoyan capsule. Objective: To study the contents of total arsenic, total mercury, soluble arsenic and soluble mercury
in Compound Niuhuang Xiaoyan capsule. Methods: Microwave digestion and semi-bionic extraction were used to pretreat the samples of Compound Niuhuang Xiaoyan capsule, and the inductively coupled plasma mass spectrometry method was established to determine the contents of total arsenic,
total mercury, soluble arsenic and soluble mercury in Compound Niuhuang Xiaoyan capsule. The accuracy of the established method was further evaluated by using a certified standard reference material prepared from dried citrus leaves (GBW10020(GSB-11)). Results: The spiked recoveries were
within 95-105 %. The R.S.D% of repeatability (N=6) and precision (N = 6) were below 5.0 %. The correlation coefficients of linear (R) for arsenic and mercury were both above 0.998. The limits of quantification (LOQ) were below 0.1 μg/L. The contents of As and Hg were defined in the dried
citrus leaves and very near to the standard values provided by the manufacturer. The established method was applied for the analysis of three batches of Compound Niuhuang Xiaoyan capsule produced by three different manufacturers successfully. Insufficient realgar or cinnabar was formulated
in some Compound Niuhuang Xiaoyan capsule samples. Conclusion: The analysis showed that the contents of soluble arsenic and soluble mercury in artificial gastric juice were significantly less than that of total arsenic and total mercury in Compound Niuhuang Xiaoyan capsule. The results
provided a reference for further study on the toxicology and pharmacokinetics of Compound Niuhuang Xiaoyan capsule.
研究领域:
中药学
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分析化学
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毒理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）