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  1. Article ; Online: Cinnabar-containing Chinese medicine Hua-Feng-Dan differs from mercury sulfide and mercury chloride in affecting gut microbiota in mice

    Yong-Mei Liu / Bo Liu / Jie Liu / Shang-Fu Xu / Feng Zhang / Ming-Liang Cheng / Jing-Shan Shi

    Pharmacological Research - Modern Chinese Medicine, Vol 8, Iss , Pp 100279- (2023)

    2023  

    Abstract: Introduction: Cinnabar (96% HgS) is included in Chinese medicines, including Hua-Feng-Dan. We have shown the protective effects of Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity in rats and against LPS plus MPTP-induced neuroinflammation in ...

    Abstract Introduction: Cinnabar (96% HgS) is included in Chinese medicines, including Hua-Feng-Dan. We have shown the protective effects of Hua-Feng-Dan against LPS plus rotenone-induced neurotoxicity in rats and against LPS plus MPTP-induced neuroinflammation in mice by modulation of gut microbiota. However, the effects of HgS-containing Hua-Feng-Dan in comparison to HgS and HgCl2 are unknown. Methods: Mice were given orally with Hua-Feng-Dan at clinical doses (0.6 and 1.5 g/kg), approximate Hg as HgS or HgCl2 for 7 days. Intestinal histology and Hg accumulation were examined. Bacterial DNA from the colon contents was extracted and subjected to DNA sequencing and qPCR verification with 16S rRNA probes. Results: Hua-Feng-Dan and HgS did not affect animal body weight gain, intestinal histology, nor produce overt intestinal Hg accumulation (2-fold). In contrast, HgCl2 reduced body weight gain, produced spotted mild inflammation, and produced 20-fold Hg accumulation in the duodenum. Operational taxonomic unit (OTU) from DNA sequencing showed that at phyla levels, HgS increased Firmicutes and decreased Bacteroidetes, while HgCl2 produced opposite effects; at the family levels, Hua-Feng-Dan increased Streptococcaceae and Dehalobacteriaceae, HgS had similar effects; at the genus levels, Hua-Feng-Dan and HgS increased Streptococcaceae__garvieae and Paraprevotellaceae__Prevotella, while HgCl2 increased Dehalobacteriaceae__Dehalobacterium and Odoribacteraceae__Odoribacter. HgS also increased Verrucomicrobiaceae__Akkermansia and produced many other alterations. Discussion: Cinnabar-containing Hua-Feng-Dan had minimal effects on animal health, gut histology and Hg accumulation but produced modulations of gut microbiota. Effects of Hua-Feng-Dan on gut microbiota were different from HgS and HgCl2.
    Keywords Cinnabar-containing Hua-Feng-Dan ; HgS ; HgCl2 ; Intestine histology ; Hg accumulation ; Gut microbiota ; Other systems of medicine ; RZ201-999 ; Therapeutics. Pharmacology ; RM1-950
    Subject code 501
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice [version 2; peer review

    Yu Nie / Shang-Fu Xu / Yan-Liu Lu / Xiu-Rong Zhao / Cen Li / Li-Xin Wei / Jie Liu

    F1000Research, Vol

    2 approved]

    2021  Volume 10

    Abstract: Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized ...

    Abstract Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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

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

    PeerJ, Vol 7, p e

    2019  Volume 7429

    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.
    Keywords mRNA/protein expression ; Ontogeny ; Aging ; Cytochrome P450’s ; Nuclear receptors ; Rat liver ; Medicine ; R
    Subject code 612
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats

    Zhu, Qiong-Ni / Jie Liu / Shang-Fu Xu / Wei-Yu Hou / Yuan-Fu Lu

    Life sciences. 2017 Feb. 01, v. 170

    2017  

    Abstract: Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and ... ...

    Abstract Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and result in changes in drug disposition.This study was aimed to examine the development-, aging-, and sex-dependent changes in Mrp1–4 and ATP-binding cassette sub-family G member 2 (Abcg2) gene expressions in livers of rats.The livers from male and female SD rats at development (−2, 1,7,14,21,28,35, and 60d) and aging (28, 60, 180 and 540d) were collected and total RNA was isolated, purified and subjected to real-time RT-PCR analysis.Results showed that expression of Mrp1 was low, while Abcg2 and Mrp2 were the high in the liver. Mrp1 expression decreased with maturity but remained constant to 540d, while Mrp3 and 4 increased with liver development, reached the peak with maturity at 35–60days of age, and slightly reduced with aging. Mrp2 and Abcg2 were high at 7days of age and maintained at relative high levels till maturity, while Abcg2 was reduced during aging. Females had higher Mrp3 and Abcg2 mRNA expression than male rats, while male rats had higher Mrp2 and Mrp4 mRNA expression.The expression of hepatic Mrp1–4 and Abcg2 mRNA during development, aging in male and female rats was characterized, which could be fundamental to our understanding of age- and sex-associated variations in drug disposition in children, elderly, and women.
    Keywords ABC transporters ; children ; drugs ; elderly ; females ; gene expression ; genes ; liver ; males ; messenger RNA ; multiple drug resistance ; ontogeny ; quantitative polymerase chain reaction ; rats ; reverse transcriptase polymerase chain reaction ; women ; xenobiotics
    Language English
    Dates of publication 2017-0201
    Size p. 108-114.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2016.11.022
    Database NAL-Catalogue (AGRICOLA)

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