The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jie Liu - One of the best experts on this subject based on the ideXlab platform.
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protective role of cinnabar and Realgar in hua feng dan against lps plus rotenone induced neurotoxicity and disturbance of gut microbiota in rats
Journal of Ethnopharmacology, 2020Co-Authors: Ce Chen, Jie Liu, Binbin Zhang, Feng ZhangAbstract:Abstract Ethnopharmacological relevance Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and Realgar (As4S4). The ethnopharmacological basis of cinnabar and Realgar in HFD is not known. Aim of the study: To address the role of cinnabar and Realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. Materials and methods Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. Results LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% Realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% Realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and Realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. Conclusion Cinnabar and Realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.
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a review of cinnabar hgs and or Realgar as4s4 containing traditional medicines
Journal of Ethnopharmacology, 2018Co-Authors: Jie Liu, Jing-zhen Shi, Qi Wang, Lixin Wei, Feng Zhang, George M CherianAbstract:Abstract Ethnopharmocological relevance Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries. Aim of the review This review uses cinnabar (HgS) and Realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives. Materials and methods A literature search on cinnabar and Realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and Realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly Realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed. Results Both cinnabar and Realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or Realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired. Conclusion Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.
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a review of cinnabar hgs and or Realgar as 4 s 4 containing traditional medicines
Journal of Ethnopharmacology, 2018Co-Authors: Jie Liu, Jing-zhen Shi, Qi Wang, Lixin Wei, Feng Zhang, George M CherianAbstract:Abstract Ethnopharmocological relevance Herbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries. Aim of the review This review uses cinnabar (HgS) and Realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives. Materials and methods A literature search on cinnabar and Realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and Realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly Realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed. Results Both cinnabar and Realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or Realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired. Conclusion Chemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.
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Realgar quantum dots induce apoptosis and necrosis in hepg2 cells through endoplasmic reticulum stress
Biomedical Reports, 2015Co-Authors: Yu Qin, Huan Wang, Zheng Yun Liu, Jie LiuAbstract:Realgar (As4S4) has been used in traditional Chinese medicines for treatment of malignancies. However, the poor water solubility of Realgar limits its clinical application. To overcome this problem, Realgar quantum dots (RQDs; 5.48±1.09 nm) were prepared by a photoluminescence method. The mean particle size was characterized by high-resolution transmission electron microscopy and scanning electron microscopy. Our recent studies revealed that the RQDs were effective against tumor growth in tumor-bearing mice without producing apparent toxicity. The present study investigated their anticancer effects and mechanisms in human hepatocellular carcinoma (HepG2) cells. The HepG2 cells and human normal liver (L02) cells were used to determine the cytotoxicity of RQDs. The portion of apoptotic and dead cells were measured by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Apoptosis-related proteins and genes were examined by western blot analysis and reverse transcription-quantitative polymerase chain reaction, and the mitochondrial membrane potential was assayed by confocal microscope with JC-1 as a probe. RQDs exhibited cytotoxicity in a concentration-dependent manner and HepG2 cells were more sensitive compared with normal L02 cells. At 15 µg/ml, 20% of the cells were apoptotic, while 60% of the cells were necrotic at 30 µg/ml. The anti-apoptosis protein Bcl-2 was dose-dependently decreased, while pro-apoptotic protein Bax was increased. There was a loss of mitochondrial membrane potential and expression of the stress genes C/EBP-homologous protein 10 and glucose-regulated protein 78 was increased by RQDs. RQDs were effective in the inhibition of HepG2 cell proliferation and this effect was due to induction of apoptosis and necrosis through endoplasmic reticulum stress.
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Role of cinnabar and Realgar of WSHFD in protecting against LPS-induced neurotoxicity.
Journal of ethnopharmacology, 2011Co-Authors: Feng Zhang, Junwen Yan, Jingshan Shi, Jie LiuAbstract:Abstract Ethnopharmacological relevance Wan-Sheng-Hua-Feng-Dan (WSHFD) is a traditional Chinese medicine used for the treatment of neurological disorders. Cinnabar (HgS) and Realgar (As 4 S 4 ) are included in WSHFD. Are they remedies or poisons? Aim of study To investigate the role of cinnabar and Realgar in the protective effects of WSHFD on lipopolysaccharide (LPS)-induced neurotoxicity. Materials and methods Rat primary midbrain neuron-glia cultures were used to explore the effects of WSHFD on LPS-induced dopamine (DA) neurodegeneration. The experiment was randomly divided into control, LPS, LPS + removed (cinnabar and Realgar in WSHFD were removed), LPS + reduced (cinnabar and Realgar in WSHFD were reduced by 65%) and LPS + original (10% cinnabar and 10% Realgar in WSHFD) groups. Dopaminergic neurotoxicity was assessed by [ 3 H]DA uptake assay and the quantification of tyrosine hydroxylase (TH)-positive neurons. Microglial activation was evaluated using an anti-OX-42 antibody. The release of intracellular reactive oxygen species (ROS) was quantified via the DCFH-DA probe. The transcripts and production of pro-inflammatory factors were examined by real-time RT-PCR analysis and ELISA, respectively. Results WSHFD (original) significantly attenuated LPS-induced decrease of DA uptake capacity and TH-positive neuron number, inhibited microglial activation, decreased LPS-induced ROS production, ameliorated LPS-induced elevations of the mRNA expressions of TNFα, iNOS, IL-1β and COX-2 and the subsequent production of TNFα, NO, IL-1β and PGE 2 in neuron-glia cultures. However, WSHFD (removed) and (reduced) failed to protect against LPS-induced neurotoxicity. Conclusion Cinnabar and Realgar were active ingredients of WSHFD in producing protective effects against LPS-induced neurotoxicity.
Xin Wang - One of the best experts on this subject based on the ideXlab platform.
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Realgar increases defenses against infection by enterococcus faecalis in caenorhabditis elegans
Journal of Ethnopharmacology, 2021Co-Authors: Juan Yue, Xin Wang, Shu Liang, Meng Gao, Na Cui, Dejuan ZhiAbstract:Abstract Ethnopharmacological relevance Realgar has been used in traditional remedies for a long history in China and India. It is clinically used to treat diverse cancers, especially acute promyelocytic leukemia (APL), chronic myelogenous leukemia (CML) in China. However, paradoxic roles of Realgar to increase or decrease immunity are reported. It is urgent to address this question, due to immune depression can be strongly benefit to cancer development, but detrimental to patients. Aim of the study This present work is to explore whether Realgar promote or suppress immune responses, and shed light on its mode of action. Our results should provide cues for rational strategy to explore Realgar for clinical use. Material and methods Infection model in vivo was established by using Enterococcus faecalis to attack Caenorhabditis elegans, then Realgar was used to treat the infected worms to investigate its effects on infectivity and the underlying mechanism. Killing analysis was carried out to test whether Realgar can mitigate worm infection. Thermotolerance resistance analysis was used to evaluate if Realgar functions hormetic effect. Quantification of live E. faecalis in nematode intestine was employed to ascertain if Realgar alleviate the bacterial load in worm gut. Quantitative real-time PCR (qRT-PCR) was used to test the expression of antibacterial effectors. Western blot was used to test the effect of Realgar on the expressions of p38 and phospho-p38 in worms infected by E. faecalis. Results Realgar alleviated the infected worms in strains of N2, glp-4, and daf-2, but failed in sek-1, glp-4; sek-1, and daf-2; daf-16 when p38 MAPK or daf-16 was blocked or inactivated. Western blot assay demonstrated that Realgar increased the expression of phosph-p38. Thermotolerance assay showed that Realgar played a hormetic role on nemtodes, triggered protective response and reduced bacterial load after Realgar treatment for 120 h qRT-PCR demonstrated that Realgar significantly increased antibacterial effectors, thus leading to pathogen elimination. Conclusion Realgar increased defenses against E. faecalis in C. elegans by inducing both immune responses and protective responses. It was regulated by p38 MAPK pathway and DAF-16.
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the mechanism of microwave induced mineral transformation and stabilization of arsenic in Realgar tailings using ferrous sulfate
Chemical Engineering Journal, 2020Co-Authors: Zezhou Zhao, Xin Wang, He Zhang, Linling Wang, Jing Chen, Huijie Hou, Yao Shi, Dengke Yao, Jing Liu, John C CrittendenAbstract:Abstract The mechanism of MW irradiation for the enhancement of the long-term stability of arsenic (As) in FeSO4-treated Realgar tailings was studied. The efficiency of As stabilization reached 99.5% in the MW-FeSO4-air system, 1.35–fold of that in the FeSO4-air system (71.8%). The increased As stability in Realgar tailings was attributed to the enhanced transformation of more stable Fe–As minerals (e.g. symplesite) from unstable Ca/S–As minerals (pharmacolite and Realgar). The oxidation of Realgar was accelerated by reactive oxygen species (ROS) through the activation of molecular oxygen with FeII of FeSO4 due to the MW athermal effect in the MW-FeSO4-air system. H+ ions from Realgar oxidation and FeSO4 hydrolysis facilitated the dissolution of pharmacolite. The released As was captured by the formed ferric oxyhydroxide. “Hot spots” on FeSO4 in MW field initiated the microstructural evolution to Fe–As crystalline minerals due to the MW thermal effect. The introduction of FeSO4 and oxygen promoted the generation of ROS and “hot spots” in MW field, which contributed to the transformation from Ca/S–As minerals to Fe–As crystalline minerals and was of great significance for the long-term stability of As in Realgar tailings.
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Realgar transforming solution induced differentiation of nb4 cell by the degradation of pml rarα partially through the ubiquitin proteasome pathway
Archives of Pharmacal Research, 2019Co-Authors: Yang Hai, Xin Wang, Peng Song, Longhe Zhao, Fei Xie, Xiangmin Tan, Qinjian XieAbstract:PML/retinoic acid receptor alpha (RARα), as a hallmark of acute promyeloid leukemia (APL), is directly related to the outcome of clinical APL remedy. It is reported that arsenicals can effectively degrade PML/RARα, such as arsenic trioxide and Realgar. However, the high toxicity or insolubility have hampered their clinical applications. Realgar transforming solution (RTS) was produced from Realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significant anti-cancer ability on chronic myeloid leukemia through oncoprotein degradation. The capacity of RTS on treating APL is what is focused on in this study. The results showed that RTS had a noticeable sensitivity in NB4 cell, and RTS remarkably down-regulated PML/RARα expression and induced cell differentiation. Further, RTS could accumulate PML/RARα into the nuclear bodies and then execute degradation, which could be reversed by proteasome inhibitor MG132. The results also exhibited that the reduction of RTS-induced PML/RARα expression accompanied by the elevation of ubiquitin and SUMO-1 protein expression. Finally, PML and SUMO-1 had been demonstrated to be co-localized after RTS treatment by immunofluorescence co-localization assay and immunoprecipitation assay. In conclusion, these results suggested that RTS-induced cell differentiation may attribute to the PML/RARα degradation partially through the ubiquitin-proteasome pathway.
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transformation of arsenic during Realgar tailings stabilization using ferrous sulfate in a pilot scale treatment
Science of The Total Environment, 2019Co-Authors: Xin Wang, He Zhang, Linling Wang, Jing Chen, Huijie Hou, Yao Shi, Jingdong Zhang, Daniel C W Tsang, John C CrittendenAbstract:Abstract Massive Realgar tailings abandoned in mining areas in China have caused serious arsenic (As) pollution seeking for urgent disposal. Stabilization treatment is a feasible strategy, however, stabilization technologies for Realgar tailings, that are Fe-deficient, Ca-rich and S-rich, have not been well developed to date. In this study, we conducted a pilot-scale stabilization treatment of Realgar tailings via ferrous sulfate addition to evaluate the transformation of As during stabilization. We found that Si, As, Ca, and S were the predominant elements in the raw Realgar tailings with a low content of Fe, and Realgar (AsII4S4) and pharmacolite (CaHAsVO4·2H2O) were the main As-bearing minerals. After the ferrous sulfate treatment, the As leaching concentration of Realgar tailings was successfully reduced from 135 mg/L to a level below the Chinese regulatory limit (2.5 mg/L). Based on the results of leaching tests, sequential extraction analysis, XRD, SEM-EDS, XPS, and thermodynamic modeling, we concluded that ferrous sulfate addition enhanced the transformation of Ca–As and S–As species to more stable Fe–As species, e.g., crystalline symplesite and amorphous Fe–As complex. Dissolution of pharmacolite was facilitated by H+ and SO42− derived from the hydrolysis and oxidation of ferrous sulfate, and oxidation of Realgar could be promoted by reactive oxygen species (ROSs) from Fe(II) oxygenation. This study improved our understanding of As transformation pathways in Realgar tailings during ferrous sulfate treatment, which could serve as an alternative scheme for Realgar tailings stabilization.
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autophagy enhanced antitumor effect in k562 and k562 adm cells using Realgar transforming solution
Biomedicine & Pharmacotherapy, 2018Co-Authors: Xin Wang, Peng Song, Dejuan Zhi, Qinjian Xie, Longhe Zhao, Baoqiang Chen, Yang Hai, Ullah InamAbstract:Realgar transforming solution (RTS) can be produced from a biotransformation process by using microorganisms cultured with Realgar in our lab. RTS has been demonstrated as a novel arsenic anti-leukemia agent in K562 and K562/ADM. However, its underlying mechanism is unclear. In this study, we showed that RTS could strongly induce apoptosis in K562 and K562/ADM cells. After the cells were treated by RTS, apoptotic population were increased compared to control and clearly distinguishable by DAPI nuclei staining. With increasing the dose of RTS, more cells arrested in S phase and G2/M phase. Secondly, we also showed that RTS could induce autophagy via up-regulation of LC3, p62/SQSTM1 and inhibition of mTOR in a much lower arsenic dosage in contrast to ATO and Realgar. In addition, autophagy induced by RTS partially due to the degradation of fusion oncoprotein Bcr-Abl, which is associated with multidrug resistant in (MDR)-CML. Our results also showed that the apoptotic rate decreased when autophagic flux was attenuated by CQ via inhibiting cleaved-caspase-3 and alleviating Bcl-2 level. These suggested that RTS triggered autophagy is a pro-death process in CML and MDR-CML cells. In conclusion, our findings demonstrated that RTS could serve as a promising arsenic candidate for anti-CML/MDR-CML by inducing apoptosis and autophagy and is more potent than ATO and Realgar.
Qiu Yan Chen - One of the best experts on this subject based on the ideXlab platform.
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effects of Realgar tetra arsenic tetra sulfide on malignant tumor cells
Journal of Clinical Oncology, 2011Co-Authors: Shuhui Chen, J Liu, Lie Zheng, Liulu Zhang, W Shen, Yihong Yao, Qiu Yan ChenAbstract:e13525 Background: Realgar, of which the main component is tetra-arsenic tetra-sulfide, has been widely used in Chinese traditional medicine. Its therapeutic effects in traditional remedies include...
Qinjian Xie - One of the best experts on this subject based on the ideXlab platform.
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Realgar transforming solution induced differentiation of nb4 cell by the degradation of pml rarα partially through the ubiquitin proteasome pathway
Archives of Pharmacal Research, 2019Co-Authors: Yang Hai, Xin Wang, Peng Song, Longhe Zhao, Fei Xie, Xiangmin Tan, Qinjian XieAbstract:PML/retinoic acid receptor alpha (RARα), as a hallmark of acute promyeloid leukemia (APL), is directly related to the outcome of clinical APL remedy. It is reported that arsenicals can effectively degrade PML/RARα, such as arsenic trioxide and Realgar. However, the high toxicity or insolubility have hampered their clinical applications. Realgar transforming solution (RTS) was produced from Realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significant anti-cancer ability on chronic myeloid leukemia through oncoprotein degradation. The capacity of RTS on treating APL is what is focused on in this study. The results showed that RTS had a noticeable sensitivity in NB4 cell, and RTS remarkably down-regulated PML/RARα expression and induced cell differentiation. Further, RTS could accumulate PML/RARα into the nuclear bodies and then execute degradation, which could be reversed by proteasome inhibitor MG132. The results also exhibited that the reduction of RTS-induced PML/RARα expression accompanied by the elevation of ubiquitin and SUMO-1 protein expression. Finally, PML and SUMO-1 had been demonstrated to be co-localized after RTS treatment by immunofluorescence co-localization assay and immunoprecipitation assay. In conclusion, these results suggested that RTS-induced cell differentiation may attribute to the PML/RARα degradation partially through the ubiquitin-proteasome pathway.
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autophagy enhanced antitumor effect in k562 and k562 adm cells using Realgar transforming solution
Biomedicine & Pharmacotherapy, 2018Co-Authors: Xin Wang, Peng Song, Dejuan Zhi, Qinjian Xie, Longhe Zhao, Baoqiang Chen, Yang Hai, Ullah InamAbstract:Realgar transforming solution (RTS) can be produced from a biotransformation process by using microorganisms cultured with Realgar in our lab. RTS has been demonstrated as a novel arsenic anti-leukemia agent in K562 and K562/ADM. However, its underlying mechanism is unclear. In this study, we showed that RTS could strongly induce apoptosis in K562 and K562/ADM cells. After the cells were treated by RTS, apoptotic population were increased compared to control and clearly distinguishable by DAPI nuclei staining. With increasing the dose of RTS, more cells arrested in S phase and G2/M phase. Secondly, we also showed that RTS could induce autophagy via up-regulation of LC3, p62/SQSTM1 and inhibition of mTOR in a much lower arsenic dosage in contrast to ATO and Realgar. In addition, autophagy induced by RTS partially due to the degradation of fusion oncoprotein Bcr-Abl, which is associated with multidrug resistant in (MDR)-CML. Our results also showed that the apoptotic rate decreased when autophagic flux was attenuated by CQ via inhibiting cleaved-caspase-3 and alleviating Bcl-2 level. These suggested that RTS triggered autophagy is a pro-death process in CML and MDR-CML cells. In conclusion, our findings demonstrated that RTS could serve as a promising arsenic candidate for anti-CML/MDR-CML by inducing apoptosis and autophagy and is more potent than ATO and Realgar.
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properties of Realgar bioleaching using an extremely acidophilic bacterium and its antitumor mechanism as an anticancer agent
Biological Research, 2017Co-Authors: Peng Chen, Xin Wang, Lei Yan, Wenbin Zhao, Yan Wei, Qinjian XieAbstract:Realgar is a naturally occurring arsenic sulfide (or Xionghuang, in Chinese). It contains over 90% tetra-arsenic tetra-sulfide (As4S4). Currently, Realgar has been confirmed the antitumor activities, both in vitro and in vivo, of Realgar extracted using Acidithiobacillus ferrooxidans (A. ferrooxidans). Bioleaching, a new technology to greatly improve the use rate of arsenic extraction from Realgar using bacteria, is a novel methodology that addressed a limitation of the traditional method for Realgar preparation. The present systematic review reports on the research progress in Realgar bioleaching and its antitumor mechanism as an anticancer agent. A total of 93 research articles that report on the biological activity of extracts from Realgar using bacteria and its preparation were presented in this review. The Realgar bioleaching solution (RBS) works by inducing apoptosis when it is used to treat tumor cells in vitro and in vivo. When it is used to treat animal model organisms in vivo, such as mice and Caenorhabditis elegans, tumor tissues grew more slowly, with mass necrosis. Meanwhile, the agent also showed obvious inhibition of tumor cell growth. Bioleaching technology greatly improves the utilization of Realgar and is a novel methodology to improve the traditional method.
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anti tumor effects and apoptosis induction by Realgar bioleaching solution in sarcoma 180 cells in vitro and transplanted tumors in mice in vivo
Asian Pacific Journal of Cancer Prevention, 2014Co-Authors: Qinjian Xie, Xinli Cao, Lu BaiAbstract:Background: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Materials and Methods: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. Results: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.
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biological extraction of Realgar by acidithiobacillus ferrooxidans and its in vitro and in vivo antitumor activities
Pharmaceutical Biology, 2010Co-Authors: Xu Zhang, Xin Wang, Qinjian Xie, Bo WangAbstract:Acidithiobacillus ferrooxidans is a Gram-negative, chemolithoautotrophic bacterium involved in metal bioleaching. It is used for the extraction of coarse medical Realgar, which is converted into an aqueous solution. To prove its feasibility as an anticancer drug candidate, extracted Realgar (ER/Af) was evaluated for its antitumor activities both in vitro and in vivo. In cytotoxicity tests, ER/Af displayed significant inhibition on cell proliferation of HepG2, SMMC7721, and H22 cells in a time and dose dependent manner. Remarkable tumor growth inhibition and survival time prolongation effects, along with no obvious toxicity, were observed in antitumor experiments against H22 cell-bearing mice. Apoptosis induction was also confirmed as one of the mechanisms involved in the efficacy of ER/Af both in vitro and in vivo. The most important observation is that ER/Af showed high selective affinity to tumor tissues with about eight-fold higher arsenic accumulations at the tumor site of mice than those of the arsenic trioxide (ATO)-treated group at the same dose (57.8 +/- 3.34 microg/g dry tissue vs. 7.6 +/- 0.88 microg/g dry tissue). In conclusion, A. ferrooxidans could be successfully used for the extraction of Realgar and ER/Af was proved to be a promising anticancer drug candidate, which is valuable for further study and clinical trials.
Yitao Wang - One of the best experts on this subject based on the ideXlab platform.
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uplc q tofms based metabolomics approach to reveal the protective role of other herbs in an gong niu huang wan against the hepatorenal toxicity of cinnabar and Realgar
Frontiers in Pharmacology, 2018Co-Authors: Fangbo Xia, Yushuang Chai, Xiao Xiao, Jianbo Wan, Yitao WangAbstract:An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM) recipe containing cinnabar (HgS) and Realgar (As2S2). However, the application of AGNH is limited by the hepato- and nephrotoxicity of cinnabar and Realgar. It should be noted that cinnabar and Realgar in AGNH are not used alone, but rather combined with other herbs as formula to use. In this study, the protective effects and mechanisms of the other herbs in AGNH against the hepatorenal toxicity induced by cinnabar and Realgar were investigated. The combination use of the other herbs in AGNH alleviated inflammatory cell infiltration and damage in the liver and kidney and restored the disturbed serum metabolic profile induced by cinnabar and Realgar insults. By UPLC/Q-TOFMS combined with pattern recognition approaches, we identified 41 endogenous metabolites in the sera of mice that were related to the hepatorenal toxicity of cinnabar and Realgar, 36 of which were restored to normal levels when various kinds of herbs were combined as compound recipe. These metabolites function as modulators in inflammation-associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid, and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs) were the most elevated among all of the metabolites detected after cinnabar and Realgar treatment, while these LysoPCs did not show overt differences between the AGNH and saline control groups, which was associated with relatively unaffected or even up-regulated expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH could have a protective effect against cinnabar- and Realgar-induced hepatic and renal damage via modulating the disordered homeostasis of the glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and sphingolipid metabolism.
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UPLC/Q-TOFMS-Based Metabolomics Approach to Reveal the Protective Role of Other Herbs in An-Gong-Niu-Huang Wan Against the Hepatorenal Toxicity of Cinnabar and Realgar
Frontiers Media S.A., 2018Co-Authors: Fangbo Xia, Yushuang Chai, Xiao Xiao, Jianbo Wan, Yitao WangAbstract:An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM) recipe containing cinnabar (HgS) and Realgar (As2S2). However, the application of AGNH is limited by the hepato- and nephrotoxicity of cinnabar and Realgar. It should be noted that cinnabar and Realgar in AGNH are not used alone, but rather combined with other herbs as formula to use. In this study, the protective effects and mechanisms of the other herbs in AGNH against the hepatorenal toxicity induced by cinnabar and Realgar were investigated. The combination use of the other herbs in AGNH alleviated inflammatory cell infiltration and damage in the liver and kidney and restored the disturbed serum metabolic profile induced by cinnabar and Realgar insults. By UPLC/Q-TOFMS combined with pattern recognition approaches, we identified 41 endogenous metabolites in the sera of mice that were related to the hepatorenal toxicity of cinnabar and Realgar, 36 of which were restored to normal levels when various kinds of herbs were combined as compound recipe. These metabolites function as modulators in inflammation-associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid, and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs) were the most elevated among all of the metabolites detected after cinnabar and Realgar treatment, while these LysoPCs did not show overt differences between the AGNH and saline control groups, which was associated with relatively unaffected or even up-regulated expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH could have a protective effect against cinnabar- and Realgar-induced hepatic and renal damage via modulating the disordered homeostasis of the glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and sphingolipid metabolism
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Image_2_UPLC/Q-TOFMS-Based Metabolomics Approach to Reveal the Protective Role of Other Herbs in An-Gong-Niu-Huang Wan Against the Hepatorenal Toxicity of Cinnabar and Realgar.PDF
2018Co-Authors: Fangbo Xia, Yushuang Chai, Xiao Xiao, Jianbo Wan, Yitao WangAbstract:An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM) recipe containing cinnabar (HgS) and Realgar (As2S2). However, the application of AGNH is limited by the hepato- and nephrotoxicity of cinnabar and Realgar. It should be noted that cinnabar and Realgar in AGNH are not used alone, but rather combined with other herbs as formula to use. In this study, the protective effects and mechanisms of the other herbs in AGNH against the hepatorenal toxicity induced by cinnabar and Realgar were investigated. The combination use of the other herbs in AGNH alleviated inflammatory cell infiltration and damage in the liver and kidney and restored the disturbed serum metabolic profile induced by cinnabar and Realgar insults. By UPLC/Q-TOFMS combined with pattern recognition approaches, we identified 41 endogenous metabolites in the sera of mice that were related to the hepatorenal toxicity of cinnabar and Realgar, 36 of which were restored to normal levels when various kinds of herbs were combined as compound recipe. These metabolites function as modulators in inflammation-associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid, and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs) were the most elevated among all of the metabolites detected after cinnabar and Realgar treatment, while these LysoPCs did not show overt differences between the AGNH and saline control groups, which was associated with relatively unaffected or even up-regulated expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH could have a protective effect against cinnabar- and Realgar-induced hepatic and renal damage via modulating the disordered homeostasis of the glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and sphingolipid metabolism.
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Table_2_UPLC/Q-TOFMS-Based Metabolomics Approach to Reveal the Protective Role of Other Herbs in An-Gong-Niu-Huang Wan Against the Hepatorenal Toxicity of Cinnabar and Realgar.DOCX
2018Co-Authors: Fangbo Xia, Yushuang Chai, Xiao Xiao, Jianbo Wan, Yitao WangAbstract:An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM) recipe containing cinnabar (HgS) and Realgar (As2S2). However, the application of AGNH is limited by the hepato- and nephrotoxicity of cinnabar and Realgar. It should be noted that cinnabar and Realgar in AGNH are not used alone, but rather combined with other herbs as formula to use. In this study, the protective effects and mechanisms of the other herbs in AGNH against the hepatorenal toxicity induced by cinnabar and Realgar were investigated. The combination use of the other herbs in AGNH alleviated inflammatory cell infiltration and damage in the liver and kidney and restored the disturbed serum metabolic profile induced by cinnabar and Realgar insults. By UPLC/Q-TOFMS combined with pattern recognition approaches, we identified 41 endogenous metabolites in the sera of mice that were related to the hepatorenal toxicity of cinnabar and Realgar, 36 of which were restored to normal levels when various kinds of herbs were combined as compound recipe. These metabolites function as modulators in inflammation-associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid, and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs) were the most elevated among all of the metabolites detected after cinnabar and Realgar treatment, while these LysoPCs did not show overt differences between the AGNH and saline control groups, which was associated with relatively unaffected or even up-regulated expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH could have a protective effect against cinnabar- and Realgar-induced hepatic and renal damage via modulating the disordered homeostasis of the glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and sphingolipid metabolism.
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hepatorenal protective effects of medicinal herbs in an gong niu huang wan agnh against cinnabar and Realgar induced oxidative stress and inflammatory damage in mice
Food and Chemical Toxicology, 2017Co-Authors: Jingyao Zhang, Yushuang Chai, Xiao Xiao, Jianbo Wan, Songsong Wang, Yitao WangAbstract:An-Gong-Niu-Huang Wan (AGNH) is a famous traditional Chinese medicine prescription that contains cinnabar (HgS) and Realgar (As2S2); the clinical practice of AGNH is hindered because both mercury and arsenic are hepatorenal toxic metalloids. It is noted that the cinnabar and Realgar in AGNH are not used alone, but rather combined with different kinds of medicinal herbs as a formula to use. In this study, we evaluated the hepatorenal protective effects of the medicinal herbs in AGNH after co-exposure to cinnabar and Realgar for 4 weeks in mice. The combination of the herbs in AGNH alleviated cinnabar and Realgar-induced histopathological alterations and oxidative stress in the liver and kidneys. Furthermore, in cinnabar and Realgar-treated mice, the increased expression levels of inducible enzymes (COX-2 and iNOS) and proinflammatory mediators (IL-1β, TNF-α, PGE2 and NO) in the liver and kidneys were consistently down-regulated when medicinal herbs were combined as a formula. We also found that the herbs could reduce the inflammatory response by the inactivation of the MAPK and PI3K/Akt signaling pathway and the resulting blockade of NF-κB activation. Overall, our data indicates that the herbal medicines in AGNH attenuate cinnabar and Realgar-induced hepatorenal toxicity by improving antioxidant competence and suppressing inflammatory injury.
