JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2025
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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
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
✓ 已验证
DOI
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2024
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IF 3.6
Zhaoliang Hu,Xiao Wu,Yi Du,Wenyu Zou,Haijuan Dong,Min Song,Taijun Hang,Yuting Lu
Background Cinnabaris (α-HgS), a mineral traditional Chinese material medica , has been used in combination with other herbs manifesting some definite therapeutic effects for thousands of years. But the currently reported mercury poisoning incidents raised the doubts about the safety of Cinnabaris-containing traditional Chinese medicines (TCMs). Baizi Yangxin Pills (BZYXP) is a Cinnabaris-containing TCM widely used in clinical practice. This study evaluated the health risk of mercury exposure from BZYXP in healthy volunteers based on the total mercury and mercury species analysis of blood and urine after single and multiple doses of BZYXP. Methods Blood pharmacokinetics and urinary excretion studies of mercury were compared between single (9 g, once daily) and multiple doses (9 g, twice daily, continued for 7 days) of BZYXP. The whole blood and urine samples were collected at the specific points or periods after the administration of BZYXP. The total mercury and mercury species in blood and urine samples were determined by cold vapor-atomic fluorescence spectrometry (CV-AFS) and HPLC-CV-AFS, respectively. Results The mercury was excreted slowly and accumulated obviously after continuous exposure of BZYXP. Moreover, the well-known neurotoxin methylmercury (MeHg) was detected in blood samples after 7 days’ administration of BZYXP. In the urine samples, only Hg(II) was detected. Therefore, long-term use of BZYXP will cause mercury poisoning due to mercury's high accumulative properties and MeHg formation. Conclusion Cinnabaris-containing TCMs such as BZYXP should be restricted to cases in which alternatives are available, and the blood mercury species profile should be monitored during the long-term clinical medication.
研究领域:
药理学
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毒理学
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传统医学
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产品关联
DOI
PubMed
高影响因子
Neuroscience Bulletin
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2025
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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
PEST MANAGEMENT SCIENCE
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2019
·Vol. 75
·期 10
·2802-2809
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IF 3.255
Kaiyang Feng,Yuwei Yang,Xiang Wen,Shiyuan Ou,Ping Zhang,Qian Yu,Yichao Zhang,Guangmao Shen,Zhifeng Xu,Jinhang Li,Lin He
BACKGROUND Cyflumetofen is an outstanding acaricide with a novel mode of action. Tetranychus cinnabarinus , an important agricultural pest, is notorious for developing resistance to most classes of acaricides rapidly and results in enormous loss for the economy. Our previous study had pointed out glutathione S-transferase (GSTs) significantly contributed to the cyflumetofen-resistance formation in T. cinnabarinus , but the more specific mechanism needed to be further investigated. RESULTS The unstable resistance was observed in cyflumetofen-resistant strain (CyR)under acaricide-free condition. The activity of GSTs increased along with the development of resistance. The expressions of 13 GST genes were detected in CyR and susceptible strain (SS), of which six genes were overexpressed in CyR and the TcGSTm02 was selected as the representative for functional study. The expression of TcGSTm02 changed along with the resistant level of CyR with the same trend. Recombinant protein of TcGSTm02 with high activity was successfully obtained by E. coli expression system, whose activity could be inhibited by cyflumetofen (IC 50 = 0.23 mM). Recombinant TcGSTm02 could effectively decompose cyflumetofen, and catalyze GS − to conjugate with cyflumetofen. CONCLUSION All clues confirmed that GSTs strongly associated with cyflumetofen-resistance and a representative gene, TcGSTm02 , showed function on contributing the evolution of cyflumetofen-resistance in T. cinnabarinus . © 2019 Society of Chemical Industry
研究领域:
农业科学
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害虫管理
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
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IF 3.412
Bingchuan Zhang,Zhiqiang Sun,Min Lv,Hui Xu
To discover new natural-product-based potential pesticides, 85 matrinic acid/alcohol/ester derivatives were synthesized by structural modifications of a quinolizidine alkaloid matrine. N-(4-Methyl)benzylmatrinyl n-decylate (76) and N-(2-chloro)benzylmatrinyl n-undecylate (86) exhibited greater than seven-fold more pronounced acaricidal activity than matrine against Tetranychus cinnabarinus; N-(2-chloro)benzylmatrinyl benzoate (80) showed the most promising insecticidal activity against Mythimna separata. The carboxyl group of matrinic acids and introduction of n-decyl/n-undecylcarbonyl into matrinic alcohols were important for the acaricidal activity; introduction of alkyloxy into the carboxyl of matrinic acids and introduction of the electron-withdrawing groups on the N-benzyl of matrinic esters were necessary for the insecticidal activity. Through RT-PCR and qRT-PCR analysis, it was shown that the lactam ring of matrine was vital for action on VGSC; opening the lactam ring of matrine and the alkylcarbonyl of side-chain were two important factors for acting with α1, α2, and α4 nAChR subunits; α1, α2, α4, and β3 subunits may be the target of action of compound 86 against T. cinnabarinus.
研究领域:
化学
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药理学
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昆虫学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）