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realgar-Induced Apoptosis of Cervical Cancer Cell Line Siha via Cytochrome C Release and Caspase-3 and Caspase-9 Activation

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Chinese Journal of Integrative Medicine 2012年第5期18卷 359-365页

作者：程艳香刘嵘王琴李秉枢许学先胡敏陈璐付琼濮德敏洪莉 Department of Gynecology Renmin Hospital of Wuhan University Department of Obstetrics and Gynecology No.161 Air Force Hospital Department of Obstetrics and Gynecology Tongji HospitalMedical College of Wuhan University

Objective： To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods： The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method. Results： Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar. Conclusion： The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.

关键词： realgar cervical cancer apoptosis cytochrome c caspases

Liver metabonomics study on the protective effect of glycyrrhetinic acid against realgar-induced liver injury

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Chinese Journal of Natural Medicines 2020年第2期18卷 138-147页

作者： HUO Tao-Guang FANG Ying ZHANG Ying-Hua FENG Cong JIANG Hong Department of Health Laboratory Technology School of Public HealthChina Medical UniversityShenyang 110122China

Glycyrrhetinic acid(GA)is the bioactive ingredient in Glycyrrhizae Radix et *** previous study has reported that GA has protective effect on realgar-induced ***,the details of the hepatoprotective mechanisms of GA on realgar-induced liver injury remain to be *** the study,mice were divided into control,GA-control,realgar,and co-treated *** liver tissues were used for metabonomics study by ultra-performance liquid chromatography-mass spectrometry(UPLCMS)*** results illustrate that GA significantly ameliorate the liver injury and metabolic perturbations caused by *** metabolites,such as phenylalanine,pyroglutamic acid(PGA),proline,carnitine,nicotinamide,choline,lysophosphatidylcholine(LPC)16:0 and LPC 18:2 were found responsible for the hepatoprotective effect of *** metabolites are associated with the methylation metabolism of arsenic,cell membrane structure,energy metabolism and oxidative *** the results of this study,we infer that the potential hepatoprotective mechanism of GA on realgar-induced liver injury may be associated with reducing arsenic accumulation and its methylation metabolism in the liver,promoting the conjugation of arsenic and GSH to play detoxification effect,and ameliorating the liver metabolic perturbations caused by realgar.

关键词： Metabonomics Glycyrrhetinic acid realgar Liver UPLC-MS

High-pressure investigations on the isostructural phase transition and metallization in realgar with diamond anvil cells

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Geoscience Frontiers 2021年第2期12卷 1031-1037页

作者： Linfei Yang Lidong Dai Heping Li Haiying Hu Meiling Hong Xinyu Zhang Pengfei Liu Key Laboratory of High-Temperature and High-Pressure Study of the Earth’s Interior Institute of GeochemistryChinese Academy of SciencesGuiyangGuizhou550081China University of Chinese Academy of Sciences Beijing100049China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhouFujian350002China

The high-pressure structural,vibrational and electrical properties for realgar were investigated by in-situ Raman scattering and electrical conductivity experiments combined with first-principle calculations up to~30.8 *** was verified that realgar underwent an isostructural phase transition at~6.3 GPa and a metallization at a higher pressure of~23.5 *** isostructural phase transition was well evidenced by the obvious variations of Raman peaks,electrical conductivity,crystal parameters and the As–S bond *** phase transition of metallization was in closely associated with the closure of bandgap rather than caused by the structural phase *** furthermore,the metallic realgar exhibited a relatively low compressibility with the unit cell volume V_(0)=718.1.4Å^(3)and bulk modulus B_(0)=36.1 GPa.

关键词： realgar Isostructural phase transition Metallization Raman spectroscopy Electrical conductivity High pressure

Studies on the biomimetic membrane interaction between liposome and realgar nanoparticles

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Science China Chemistry 2009年第9期52卷 1512-1518页

作者： SHEN XingCan JIN Tao XIE Jun LIANG Hong YAN Yu Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources Ministry of EducationCollege of Chemistry&Chemical EngineeringGuangxi Normal UniversityGuilin 541004China

The liposome of small unilamellar vesicles (SUV) made from phosphatidylcholine-cholesterol mixtures was used as a simple model for biomimetic membranes. The studies on the interaction between the liposome and realgar nanoparticles (NPs) demonstrate that the phospholipid is one of the key targeted molecules of realgar NPs, used by surface plasmon resonance (SPR) technology, fluorescence polarization, Raman spectroscopy, nuclear magnetic resonance (NMR) and atom force microscope (AFM). It was observed that the relative viscosity (ηr) of the membrane increased and the membrane fluidity decreased as realgar NPs bound to SUV. Calculations of Raman intensity ratios detected the increase of longitudinal order parameters (Strans) and lateral order parameters (Slat) of the lipid bilayer, indicating a rise in the proportion of trans conformations of alkyl chains, and the decrease of membrane’s fluidity attributed to the interaction of realgar NPs. Results of Raman spectra and 31P NMR suggest that the polar headgroup of phospholipid is the interacted target site of realgar NPs. Moreover, time-lapse AFM images show that realgar NPs compromise the phospholipid membrane integrity to result in the formation of "pore" or "hole".

关键词： realgar nanoparticles liposome biomimetic membrane interaction

Arsenic concentration in peripheral blood is correlated with efficacy of a Traditional Chinese Medicine regimen containing realgar for the treatment of myelodysplastic syndromes

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Journal of Traditional Chinese Medicine 2021年第4期41卷 630-635页

作者： WANG Dexiu XU Yonggang DU Yu WANG Hongzhi LI Liu HU Xiaomei YANG Xiupeng MA Rou ZHOU Qingbing Department of Hematology Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Institute of Geriatric Medicine Xiyuan HospitalChinese Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia(MDS-MLD)and arsenic concentration in the peripheral blood of ***:In this prospective study,a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January *** blood examination as well as liver and kidney function were monitored before and after *** concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after *** correlation between clinical effect and arsenic concentration was analyzed by Spearman’s ***:The treatment response rate was 54%.Two patients(4%)achieved complete remission,50%(25 of 50)showed hematologic improvement,and 23 patients had stable disease(23%).No disease progression was *** concentration in the peripheral blood ranged from 14.60 to 85.96μg/*** efficacy was positively correlated with arsenic concentration(Prealgar in MDS-MLD patients.

关键词： realgar arsenic myelodysplastic syndromes multiline dysplasia

Acid Water-ground Nano-realgar Is Superior to Crude realgar in Promoting Apoptosis of MCF-7 Breast Cancer Cells

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Current Medical Science 2022年第4期42卷 720-732页

作者： Juan XI Jia-hui FANG Xiao-mei XIONG Chun GUI Yu-xue WANG Xiu-qiao ZHANG School of Pharmacy Hubei University of Chinese MedicineWuhan 430065China School of Laboratory Medicine Hubei University of Chinese MedicineWuhan 430065China

Objective:realgar is a traditional mineral Chinese medicine with antitumor effects,but it has high toxicity and low efficacy in its crude *** purpose of this study was to optimize realgar to increase its efficacy and therapeutic ***:Crude realgar(CR)was mechanically ground to obtain nano-realgar(NR),and then nano-realgar processed products(NRPPs)were obtained using three different traditional Chinese medicine processing methods:grinding in water,acid water,and alkali water,***:By analyzing the size distribution of nanoparticles and the content of arsenic trioxide(As_(2)O_(3);ATO),we found that acid water-ground NRPPs had the characteristics of high purity and low *** effects of CR,NR,and NRPPs on proliferation,cell cycle,and apoptosis of MCF-7 cells were detected,and the ability of NRPPs to induce apoptosis in MCF-7 cells was *** results showed that the average particle size of acid water-ground NRPPs was 137.7 nm,and the content of ATO was 2.83 mg/*** water-ground NRPPs showed better effects on inhibiting proliferation,cell cycle,and apoptosis of MCF-7 cells than CR and *** blot assays further confirmed that acid water-ground NRPPs upregulated the protein expression of TP53,Bax,cytochrome c,caspase-9,and caspase-3 in MCF-7 cells(Prealgar.

关键词： realgar acid water-ground nano-realgar MCF-7 cells apoptosis

Advances in the Safety Evaluation of Mineral Medicines-Cinnabar and realgar

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World Journal of Traditional Chinese Medicine 2019年第3期5卷 164-172页

作者： Jing-Zhuo Tian Ai-Hua Liang Xiao-Xin Zhu Yong Zhao Yan Yi Chun-Ying Li Jia-Yin Han Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Key Laboratory of Beijing for Identification and Safety Evaluation of ChineseMedicine Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing State Key Laboratory of Innovative Natural Medicine and TCMInjections Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesGanzhouChina

Mineral medicines have a long history in the treatment of diseases. Among these, cinnabar and realgar are the most commonly used. This review discusses the differences between cinnabar and realgar and other mercurials and arsenicals. In addition, it explores the toxicity studies carried out on cinnabar and realgar, which include acute and chronic toxicity, neurotoxicological effects, special toxicity, disposition and accumulation, and the relative mechanism of toxicity. Cinnabar and realgar are seldom used alone but rather in combination with herbs or animal medicines. Thus, in this article, we have also included a study of the effect of toxicity reduction and efficacy enhancement after cinnabar and realgar were combined with other Chinese medicinal materials. This review provides the theoretical evidence for their clinical application, suggesting that the dosage and treatment period using cinnabar and realgar should be rigidly controlled and emphasis should be placed on the drug safety of special populations.

关键词： Cinnabar compound Chinese medicines disposition realgar toxicity

INVESTIGATION OF realgar IN THE TREATMENT FOR MULTIPLE MYELOMA

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Journal of Pharmaceutical Analysis 2005年第1期17卷 94-96页

作者：王梦昌刘陕西李信民 Department of Hematology First Hospital of Xi'an Jiaotong University Xi'an 710061 China

Objective To observe the clinical effect of realgar on multiple myeloma and to investigate its mechanism. Methods MTT and double antibody cramped ELISA assay were used to detect the activity of interleukin-6(IL-6) and level of soluble interleukin-6 receptor(sIL-6R) of the bone marrow supernant in 15 multiple myeloma patients treated by realgar or not. Results The activity of interleukin-6 and level of soluble interleukin-6 receptor of multiple myeloma patients were significantly higher than that of control group(Prealgar was used for 50 days(P>0.05).The interleukin-6 activity of stage Ⅲ patients were much higher than that of stage Ⅰ or Ⅱ(P0.05). For the 15 patients who were treated by using realgar, 3 got complete remission(CR), 5 got partial remission(PR), 7 came to not remission(NR). Conclusion realgar could not decrease the activity of interleukin-6 and level of soluble interleukin-6 receptor so as to inhibit the proliferation of tumor cells.

关键词： realgar multiple myeloma interleukin-6 therapy

Effects of realgar on stress proteins, inflammatory mediators, and complement in brain tissue and serum of rats with inflammatory brain injury

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Neural Regeneration Research 2008年第8期3卷 885-889页

作者： Yishan Tang Ningsheng Wang Yinqing Zhang Shaomei Ye Weiping Ou Institute of Clinical Pharmacology Guangzhou University of Traditional Chinese Medicine Guangzhou 510405 Guangdong Province China

BACKGROUND：The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways： in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE： To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING： Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS： Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows： realgar and Angong Niuhuang powder （Foshan Second Pharmaceutical Factory, China）, Bordetella pertussis diagnostic antigen （National Institute for the Control of Pharmaceutical and Biological Products, China）, heat shock protein 70 （HSP70） enzyme-labeled immunosorbent assay （ELISA） kit （Stressgen, USA）, tumor necrosis factor-α （TNF-α） ELISA kit （Biosource, USA）, nitric oxide synthase （NOS） kit, Coomassie brilliant blue protein kit （Nanjing Jiancheng Bioengineering Co.,Ltd., China）, and complements C3 and C4 （Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China）. METHODS： Thirty-six rats were randomly and evenly divided into the following six groups： normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the mo

关键词： realgar Angong Niuhuang powder stress protein inflammatory mediator complement inflammatory brain injury