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  1. Article: Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats

    Chen, Ce / Hu, An-Ling / Li, Huan / Liu, Jie / Zhang, Bin-Bin / Zhang, Feng

    Journal of ethnopharmacology. 2020 Jan. 30, v. 247

    2020  

    Abstract: 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 ... ...

    Abstract 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.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.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.Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.
    Keywords active ingredients ; animal models ; colon ; DNA ; immunohistochemistry ; intestinal microorganisms ; neurons ; neuroprotective effect ; neurotoxicity ; Oriental traditional medicine ; Parkinson disease ; quantitative polymerase chain reaction ; rats ; ribosomal RNA ; rotenone ; staining ; Verrucomicrobiaceae
    Language English
    Dates of publication 2020-0130
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2019.112299
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Antitumor effects of cadmium against diethylnitrosamine-induced liver tumors in mice.

    Nie, Yu / Huang, Bo / Hu, An-Ling / Xu, Yun-Yan / Zou, Yan / Liu, Yun / Liu, Jie

    Oncology letters

    2021  Volume 23, Issue 1, Page(s) 33

    Abstract: Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable ... ...

    Abstract Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable strategy. In the present study, 8-week old, male, C57BL/6 mice were administered injections of diethylnitrosamine (DEN) (90 mg/kg, and then 50 mg/kg 2 weeks later), followed by liver tumor promotion with carbon tetrachloride. Cadmium chloride was administered in the drinking water (1000 ppm) from 21-40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein (MT) immunostaining were performed. After DEN injection, animal body weight decreased, and then slowly recovered with time. Cd treatment did not affect animal body weight gain. Ultrasound analysis detected liver tumors 35 weeks after DEN injection, and the mice were necropsied at 40 weeks. Liver/body weight ratios increased in the DEN and DEN + Cd groups. Cd treatment decreased the tumor incidence (71 vs. 17%), tumor numbers (15 vs. 2) and tumor scores (22 vs. 3) when compared with the DEN only group. Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed MT-deficiency in the liver tumors, while MT staining was intensified in the surrounding tissues. Reverse transcription-quantitative PCR showed increases in α-fetoprotein level in DEN-treated livers, and increases in MT-2 and tumor necrosis factor α (TNFα) levels in Cd-treated livers. Thus, it was concluded that Cd is effective in the suppression of DEN-induced liver tumors, and that the mechanisms may be related to MT-deficiency in tumors and the induction of TNFα to kill tumor cells.
    Language English
    Publishing date 2021-11-26
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 2573196-8
    ISSN 1792-1082 ; 1792-1074
    ISSN (online) 1792-1082
    ISSN 1792-1074
    DOI 10.3892/ol.2021.13151
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats.

    Xu, Shang-Fu / Hu, An-Ling / Xie, Lu / Liu, Jia-Jia / Wu, Qin / Liu, Jie

    PeerJ

    2019  Volume 7, Page(s) e7429

    Abstract: Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid ... ...

    Abstract Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by western blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, five nuclear receptors, and four phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.
    Language English
    Publishing date 2019-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.7429
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Protective role of cinnabar and realgar in Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity and disturbance of gut microbiota in rats.

    Chen, Ce / Zhang, Bin-Bin / Hu, An-Ling / Li, Huan / Liu, Jie / Zhang, Feng

    Journal of ethnopharmacology

    2019  Volume 247, Page(s) 112299

    Abstract: Ethnopharmacological relevance: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As: Aim of the study: To address the role of cinnabar and realgar in HFD-produced ... ...

    Abstract Ethnopharmacological relevance: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As
    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.
    MeSH term(s) Animals ; Arsenicals/chemistry ; Arsenicals/pharmacology ; Arsenicals/therapeutic use ; DNA, Bacterial/isolation & purification ; Disease Models, Animal ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/pathology ; Drugs, Chinese Herbal/chemistry ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Enterobacteriaceae/drug effects ; Enterobacteriaceae/genetics ; Enterobacteriaceae/isolation & purification ; Ethnopharmacology ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/genetics ; Gastrointestinal Microbiome/immunology ; Humans ; Inflammation Mediators/metabolism ; Lactobacillaceae/drug effects ; Lactobacillaceae/genetics ; Lactobacillaceae/isolation & purification ; Lipopolysaccharides/toxicity ; Male ; Mercury Compounds/chemistry ; Mercury Compounds/pharmacology ; Mercury Compounds/therapeutic use ; Microglia/drug effects ; Microglia/immunology ; Microglia/pathology ; Nerve Degeneration ; Neuroprotective Agents/chemistry ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Neurotoxicity Syndromes/drug therapy ; Neurotoxicity Syndromes/etiology ; Neurotoxicity Syndromes/immunology ; Neurotoxicity Syndromes/pathology ; RNA, Ribosomal, 16S/genetics ; Rats ; Rotenone/toxicity ; Sulfides/chemistry ; Sulfides/pharmacology ; Sulfides/therapeutic use ; Verrucomicrobia/drug effects ; Verrucomicrobia/genetics ; Verrucomicrobia/isolation & purification
    Chemical Substances Arsenicals ; DNA, Bacterial ; Drugs, Chinese Herbal ; Inflammation Mediators ; Lipopolysaccharides ; Mercury Compounds ; Neuroprotective Agents ; RNA, Ribosomal, 16S ; Sulfides ; Rotenone (03L9OT429T) ; arsenic disulfide (56320-22-0) ; cinnabar (ZI0T668SF1)
    Language English
    Publishing date 2019-10-10
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2019.112299
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mercury sulfide-containing Hua-Feng-Dan and 70W (Rannasangpei) protect against LPS plus MPTP-induced neurotoxicity and disturbance of gut microbiota in mice.

    Hu, An-Ling / Song, Sheng / Li, Yi / Xu, Shang-Fu / Zhang, Feng / Li, Cen / Liu, Jie

    Journal of ethnopharmacology

    2020  Volume 254, Page(s) 112674

    Abstract: Ethnopharmacological relevance: Mercury sulfides (HgS) are frequently included in Ayurveda, Tibetan and Chinese medicines to assist the presumed therapeutic effects, but the ethnopharmacology remains elusive. The present study examined the protective ... ...

    Abstract Ethnopharmacological relevance: Mercury sulfides (HgS) are frequently included in Ayurveda, Tibetan and Chinese medicines to assist the presumed therapeutic effects, but the ethnopharmacology remains elusive. The present study examined the protective effects of α-HgS-containing Hua-Feng-Dan and β-HgS-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) against Parkinson's disease mice induced by lipopolysaccharide (LPS) plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
    Method: A single injection of LPS (5 mg/kg ip) was given to adult male C57BL/6 mice, and 150 days later, the low dose of MPTP (15 mg/kg, ip, for 4 days) was given to produce the "two-hit" Parkinson's disease model. Together with MPTP treatment, mice were fed with clinically-relevant doses of Hua-Feng-Dan (0.6 g/kg) and 70W (0.2 g/kg) for 35 days. Rotarod test was performed to examine muscle coordination capability. At the end of the experiment, brain was transcardially perfused with paraformaldehyde, the substantia nigra was sectioned for microglia (Iba1 staining) and dopaminergic neuron (THir staining) determination. Colon bacterial DNA was extracted and subjected to qPCR analysis with 16S rRNA probes.
    Results: The low-grade, chronic neuroinflammation produced by LPS aggravated MPTP neurotoxicity, as evidenced by decreased motor activity, intensified microglia activation and loss of dopaminergic neurons. Both Hua-Feng-Dan and 70W increased rotarod activity and ameliorated the pathological lesions in the brain. In gut microbiomes examined, LPS plus MPTP increased Verrucomicrobiaceae, Methanobacteriaceae, Pronicromonosporaceae, and Clostridaceae species were attenuated by Hua-Feng-Dan and 70W.
    Conclusions: α-HgS-containing Hua-Feng-Dan and β-HgS-containing 70W at clinical doses protected against chronic LPS plus MPTP-induced toxicity to the brain and gut, suggesting HgS-containing traditional medicines could target gut microbiota as a mechanism of their therapeutic effects.
    MeSH term(s) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Colon/drug effects ; Colon/microbiology ; Dopaminergic Neurons/pathology ; Lipopolysaccharides ; Male ; Mercury Compounds/pharmacology ; Mice ; Microglia/pathology ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/prevention & control ; Rotarod Performance Test ; Substantia Nigra/pathology
    Chemical Substances Lipopolysaccharides ; Mercury Compounds ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (9P21XSP91P) ; cinnabar (ZI0T668SF1)
    Language English
    Publishing date 2020-02-24
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2020.112674
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: HgS and Zuotai differ from HgCl

    Zhang, Bin-Bin / Liu, Yong-Mei / Hu, An-Ling / Xu, Shang-Fu / Fan, Li-Da / Cheng, Ming-Liang / Li, Cen / Wei, Li-Xin / Liu, Jie

    Toxicology and applied pharmacology

    2019  Volume 379, Page(s) 114615

    Abstract: Mercury (Hg) is generally considered as a toxic metal; yet the biological outcomes of Hg-containing compounds are highly dependent upon their chemical forms. We hypothesize that mercury sulfide (HgS) is different from ... ...

    Abstract Mercury (Hg) is generally considered as a toxic metal; yet the biological outcomes of Hg-containing compounds are highly dependent upon their chemical forms. We hypothesize that mercury sulfide (HgS) is different from HgCl
    MeSH term(s) Animals ; Duodenum/metabolism ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/genetics ; Ileum/metabolism ; Ileum/pathology ; Intestinal Absorption/drug effects ; Male ; Membrane Transport Proteins/drug effects ; Membrane Transport Proteins/metabolism ; Mercuric Chloride/toxicity ; Mercury Compounds/pharmacokinetics ; Mercury Compounds/toxicity ; Mice ; RNA, Ribosomal, 16S/genetics ; Real-Time Polymerase Chain Reaction
    Chemical Substances Membrane Transport Proteins ; Mercury Compounds ; RNA, Ribosomal, 16S ; zuotai ; Mercuric Chloride (53GH7MZT1R) ; cinnabar (ZI0T668SF1)
    Language English
    Publishing date 2019-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204477-8
    ISSN 1096-0333 ; 0041-008X
    ISSN (online) 1096-0333
    ISSN 0041-008X
    DOI 10.1016/j.taap.2019.114615
    Database MEDical Literature Analysis and Retrieval System OnLINE

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