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@#Cinnabaris(α-HgS) is a mineral traditional Chinese material medica, as a tranquilizer and sedative, which is widely used in combination with herbs for the treatment of children high fever and convulsion.However, a large amount of mercury in Cinnabaris poses a potential risk to the immature central nervous system of children and probably causes severe memory disorders.Inthisstudy,three groups of juvenile rats were given low, medium, and high doses of Cinnabaris by oral gavage once a day for 14 continuous weeks, respectively.The blood mercury concentrations of the rats at different growth phases were monitored by atomic fluorescence spectrometry.The brain structural and functional changes related to the memory functions were investigated through HE staining and Morris water-maze test. Correlation analysis was conducted to clarify the dose- mercury exposure-toxic effect relationship of Cinnabaris and memory disorders.It was found thatthe blood mercury levels increased in both time- and dose-dependent manner.After the 14-week continuous administration of Cinnabaris, the pathological lesions in hippocampal neurons of rats in the high dose group were observed including pyknosis and disordered cell arrangement.In the Morris water-maze test, compared with the control group, rats in the high dose group exhibited the significantly prolonged latency to find the platform and the target quadrant, and the time spent in the target quadrant was obviously shortened. Thus, the significant correlations were established between Cinnabaris dose and mercury exposure,mercury exposure and memory disorders, respectively. In conclusion, the long-term and overdose administration of Cinnabaris in juvenile rats can increase the in-vivo mercury level, destroy the normal hippocampal morphological structure, and lead to memory disorders. This study provided scientific references for the potential mercury poisoning risks pharmacovigilance of Cinnabaris-containing paediatric formulations.
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Objective To study the pharmacokinetic features of reactive sulfide in rats after oral administration of Cinnabaris. Methods An HPLC coupled with precolumn derivatization method was developed for the pharmacokinetic features study on reactive sulfide in rats after oral administration of Cinnabaris. Results Good linearity (r>0.99) was found for reactive sulfide in plasma in the concentration range of 0.25–15 μmol/L (r>0.99). The LOQ and LOD of the method were 0.1 μmol/L and 0.02 μmol/L, respectively. The intra- and inter-day precision was less than 4.4% and 3.5% respectively, and the accuracy was -9.9%–6.0%. The average recovery rate was 74.9%. 0.6 g/kg Cinnabaris was given the rats for gavage, and the time-course pharmacokinetics parameters were as follows:Cmax(1.33±0.13) μmol/L, tmax(150±34) min, t1/2(323±62) min, AUC0-∞ (5743±297) ng/mL?h. Conclusion A sensitive, robust and accurate precolumn derivatization-HPLC method for the determination of plasma reactive sulfide is developed and validated. The method is successfully applied in the pharmacokinetic features study on reactive sulfide in plasma of rats after administration of Cinnabaris.
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Mineral Chinese medicine is the distinctive part of the Chinese traditional medicine. The mineral Chinese medicines containing mercury elements such as cinnabaris, calomelas and hydrargyri oxydum rubrum are widely applied in the clinical conditions because of their efficacy of sedative, sterilization, removing necrotic tissue and promoting granulation. However, the rationality and security of clinical application are questioned because of the toxic effect caused by mercury compounds. This paper would summarize the efficacy of the mineral Chinese medicines containing mercury element, as well as their hepatotoxicity, nephrotoxicity, embryotoxicity, and neurotoxicity effect and mechanisms. Improper usage or high dose of the mineral Chinese medicines containing mercury element would cause acute hepatotoxicity. Cinnabaris, calomelas and hydrargyri oxydum rubrum may lead to chronic hepatotoxicity, nephrotoxicity, embryotoxicity and neurotoxicity when they were applied externally to the skin for long-term use. In addition to the accumulation of mercury elements in the tissues and organs, the species and forms of mercury compounds absorbed into the body in different ways, should be also studied in order to understand the toxicity of the mineral Chinese medicines containing mercury element. Meanwhile the dose and period of treatment shall be also considered in order to provide the references for rational and safe clinical application of the mineral Chinese medicines containing mercury element.
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Fufang Niuhuang Xiaoyan capsule was a classical compound prescription with the efficacy of heat-clearing, detoxification, sedation and anti-inflammation, with cinnabaris as one of its active ingredients. The study focuses on the pharmacokinetics of mercury in rats after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule, in order to explore the effect of combined traditional Chinese medicines on mercury metabolism. In this study, the method of nitric-perchloric acid digestion system coupled with cold atomic-atomic fluorescence spectroscopy (CV-AFS) was adopted to accurately determine mercury in whole blood of rats. Fufang Niuhueng Xiaoyan capsule had three dose schemes of oral administration, namely equivalent clinical dose, 3 times of equivalent clinical dose and 10 times of equivalent clinical dose; And the doses of oral administration of cinnabaris was calculated according to that of Fufang Niuhuang Xiaoyan capsule. SPF grade healthy SD rats were fasted overnight before the oral administration with cinnabaris suspension (or Fufang Niuhuang Xiaoyan capsule suspension). After oral administration of different doses of cinnabaris, no obvious changes in tmax and MRT were observed, while Cmax/dose, AUC0-48 h/dose and AUC0-∞/dose decreased with the increase in dose, indicating that total mercury absorption in body was declining. As the dose increased, Ke, CL/F decreased, and t1/2 increased, indicating that the elimination slowed down, and mercury metabolism showed non-linear dynamic characteristics within a certain range of dose (22-220 mg•kg⁻¹). The total mercury metabolism in the whole blood of rats after oral administration with different doses of Fufang Niuhuang Xiaoyan capsule also showed non-linear dynamic characteristics. The results were correlated with the low solubility of cinnabaris in the body. Compared with cinnabaris, Fufang Niuhuang Xiaoyan capsule showed no obvious changes in V/F and MRT, while Ke, CL/F, tmax decreased, and t1/2, Cmax/dose, AUC0-48 h/dose, AUC0-∞/dose increased significantly. The results showed that Fufang Niuhuang Xiaoyan capsule accelerated absorption, slowed down elimination and improved the total absorption of mercury in the whole blood, indicating that Fufang Niuhuang Xiaoyan capsule may contain components for promoting absorption and alleviating elimination of mercury. Fufang Niuhuang Xiaoyan capsule had an impact on the pharmacokinetics of cinnabaris, and long-term administration of cinnabaris (Fufang Niuhuang Xiaoyan capsule) was possible to cause accumulation of mercury in the body. This study could explain changes in efficacy of Fufang Niuhuang Xiaoyan capsule, evaluate the rationality of compound medicines containing toxic elements and provide scientific basis for the rational and safe use of Fufang Niuhuang Xiaoyan capsule.
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As a kind of mineral medicine containing mercury, the toxicity of Cinnabaris has always been controversial. In recent years, along with the increasing reports and studies on Cinnabaris, it has been found that although the toxicity of Cinnabaris has effects on multi-systems, the main effect is on nervous system. In order to clarify Cinnabaris neurotoxicity and reduce its damage for nervous lesion caused in clinical application, this article made a thorough analysis on symptom expression and mechanism of Cinnabaris neurotoxicity and put forward corresponding countermeasures.
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OBJECTIVE:To provide identification reference for the clinical use of Cinnabaris. METHODS:TCM micro-macro-scopical identification method and microscopic identification method were used. RESULTS:The micro-macroscopical characteristics were obtained:irregular granule or sheet block,different forms,wide bright red,opuque translucent with some luster; some sam-ples showed irregular lump with big shape,red scale on surface,dulling or gray-black. The were microscopic characteristics ob-tained:different forms of irregular granule,some sheet block,wide bright red,with some luster,occasionally with yellow gran-ules. CONCLUSIONS:The method for micro-macroscopical identification and microscopic identification of Cinnabaris is simple and convenient,and it can be used for the rapid verification of Cinnabaris.
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Objective To develop a HPLC-DAD method for the simultaneous determination of 20 synthetic pigments in dyed Traditional Chinese Medicine. Methods The samples were extracted with ultrasonic by 70% methanol, separated on a Agilent TC-C18 column ( 4. 6 mmí250 mm, 5 μm ) by gradient elution using a mobile phase made up of methanol and 0. 02 mol·L-1 ammonium acetate, and detected at 210-650 nm. The retention times and ultraviolet absorption spectrums were used to text and verify. Results The twenty red and orange synthetic pigments were separated and detected. OrangeIIsodium salt and 808 scarlet were detected in some batch of Croci stigma and Cinnabaris. Conclusion The method is simple, rapid, accurate, repeatable for determining twenty synthetic pigments in dyed Traditional Chinese Medicine.
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AIM:To establish a quality standard for Anshen Wendan Pill(Rhizoma Pinelliae Praeparata,Pericarpium Citri reticulatae,Poria,Radix et Rhizoma Ginseng,etc.). METHODS:Pericarpium Citri Reticulatae,Fructus Schisandrae Chinensis,Radix et Rhizoma Ginseng,and Radix et Rhizoma Glycyrrhizae were identified by TLC,and the contents of schisandrin and hesperidin were determined by HPLC. The content of cinnabaris was determined by titration. RESULTS:Pericarpium Citri reticulatae,Fructus Schisandrae Chinensis,Radix et Rhizoma Ginseng,and Radix et Rhizoma Glycyrrhizae could be identified by TLC. The calibration curve of schisandrin was linear in the range of 0.017-0.52 ?g with the correlation coefficient of 1.000 0(n=5).The average recovery of schisandrin was 99.83%(RSD=0.86%,n=6). The calibration curve of hesperidin was linear in the range 0.506 -2.53 ?g,with the correlation coefficient of 1.000 0(n=5).The average recovery hesperidin was 100.43%(RSD=1.39%,n=6). The average recovery of cinnabaris was 98.30%(RSD=1.06%,n=6). CONCLUSION :The methods are simple,accurate and reproducible. They are suitable for the quality control of Anshen Wendan Pill.
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AIM:To evaluate the actions of cinnabaris and realgar in arousing brain and opening the orifices of Angong Niuhuang Pill,and to provide experimental basis for the rationality of Angong Niuhuang Pill buildup. METHODS: The brain damage model was made by LPS injection through caudal vein.With quantitative electroencephalogram of medicine methods,effects of Angong Niuhuang Pill,Angong Niuhuang Pill without cinnabaris and realgar,cinnabaris,realgar on the power and relative power of delta and beta waves of electrocorticogram(ECoG) were observed in the brain damage rats caused by LPS. RESULTS: LPS could increase the power and the relative power of the delta waves(0.5-3 Hz),and reduce the power and the relative power of the beta waves(14-30 Hz).All medicines could reduce the power and the relative power of the delta;Angong Niuhuang Pill,cinnabaris and realgar,realgar could increase the power and the relative power of the beta,cinnabaris could increase the relative power of the beta(14-30 Hz),and Angong Niuhuang Pill without cinnabaris and realgar could not. CONCLUSION: Angong Niuhuang Pill has obvious activation on ECoG,and same as cinnabaris and realgar.The results of the present work allow us to put forward the hypothesis that cinnabaris and realgar are most likely one of the important material basis in arousing brain and opening the orifices of Angong Niuhuang Pill.
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AIM:To establish the method for quality control of Huisheng Diyidan Tablet(Eupolyphagea seu Steleophaga;Radix Angelicae sinensis,Sanguis Draconis,etc.). METHODS: Radix Angelicae sinesis,Eupolyphaga seu Steleophaga,Chinnabaris,Moschus,Boswellia carterii were identified by microscope.Sanguis Draconis was identified by TLC,Pyritum was identified by general identified reaction;The content limitation of cinnabaris(HgS) was determined by titration.Ferulic acid content of Radix Angelicae sinensis was determined by HPLC. RESULTS: Every part of the tablet was identified,the content limitation of cinnabaris(HgS) and ferulic acid content of Radix Angelicae sinensis were determined. CONCLUSION: The method showed that the characteristic for identification is distinct and highly specific,quantitative assay is simple,accurate,reliable and can be used for quality control of Huisheng Diyidan Tablet effectively.