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  1. Article ; Online: Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

    He, Qianyan / Wang, Yueqing / Fang, Cheng / Feng, Ziying / Yin, Meifang / Huang, Juyang / Ma, Yinzhong / Mo, Zhizhun

    CNS neuroscience & therapeutics

    2024  Volume 30, Issue 2, Page(s) e14634

    Abstract: Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical ... ...

    Abstract Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization. It highlights the dual role of neutrophils in tissue damage and repair, and the critical involvement of the blood-brain barrier (BBB) in stroke outcomes. Special emphasis is placed on ischemia-reperfusion injury, characterized by oxidative stress, inflammation, and endothelial dysfunction, which paradoxically exacerbates cerebral damage post-revascularization. The review also explores the potential of targeting molecular pathways involved in BBB integrity and inflammation to enhance the efficacy of recanalization therapies. By synthesizing current research, this paper aims to provide insights into optimizing treatment protocols and developing adjuvant neuroprotective strategies, thereby advancing stroke therapy and improving patient outcomes.
    MeSH term(s) Humans ; Ischemic Stroke/therapy ; Stroke/therapy ; Thrombolytic Therapy ; Thrombectomy/methods ; Inflammation ; Brain Ischemia/therapy ; Treatment Outcome
    Language English
    Publishing date 2024-04-18
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2423461-8
    ISSN 1755-5949 ; 1755-5930
    ISSN (online) 1755-5949
    ISSN 1755-5930
    DOI 10.1111/cns.14634
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Activation of Wnt/Beta-Catenin Signaling Pathway as a Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury.

    Mo, Zhizhun / Zeng, Zhongyi / Liu, Yuxiang / Zeng, Linsheng / Fang, Jiansong / Ma, Yinzhong

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 914537

    Abstract: Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ... ...

    Abstract Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ischemia/reperfusion injury. Wnt signaling is an evolutionarily conserved signaling pathway that has been manifested to play a key role in embryo development and function maintenance in adults. Overactivation of Wnt signaling has previously been investigated in cancer-based research studies. Recently, abnormal Wnt signaling activity has been observed in ischemic stroke, which is accompanied by massive blood-brain barrier (BBB) disruption, neuronal apoptosis, and neuroinflammation within the central nervous system (CNS). Significant therapeutic effects were observed after reactivating the adynamic signaling activity of canonical Wnt signaling in different cell types. To better understand the therapeutic potential of Wnt as a novel target for stroke, we reviewed the role of Wnt signaling in the pathogenesis of stroke in different cell types, including endothelial cells, neurons, oligodendrocytes, and microglia. A comprehensive understanding of Wnt signaling among different cells may help to evaluate its potential value for the development of novel therapeutic strategies based on Wnt activation that can ameliorate complications and improve functional rehabilitation after ischemic stroke.
    Language English
    Publishing date 2022-05-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.914537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Comparative Metabolomics Analysis Reveals Key Metabolic Mechanisms and Protein Biomarkers in Alzheimer's Disease.

    Dai, Zhao / Hu, Tian / Su, Shijie / Liu, Jinman / Ma, Yinzhong / Zhuo, Yue / Fang, Shuhuan / Wang, Qi / Mo, Zhizhun / Pan, Huafeng / Fang, Jiansong

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 904857

    Abstract: Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic ... ...

    Abstract Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic changes in AD, which provides insight into the identification of potential biomarkers for diagnosis, treatment, and prognostic assessment. However, since different species may lead to systemic abnormalities in metabolomic profiles, it is urgently needed to perform a comparative metabolomics analysis between AD animal models and human patients. In this study, we integrated 78 metabolic profiles from public literatures, including 11 metabolomics studies in different AD mouse models and 67 metabolomics studies from AD patients. Metabolites and enrichment analysis were further conducted to reveal key metabolic pathways and metabolites in AD. We totally identified 14 key metabolites and 16 pathways that are both differentially significant in AD mouse models and patients. Moreover, we built a metabolite-target network to predict potential protein markers in AD. Finally, we validated HER2 and NDF2 as key protein markers in APP/PS1 mice. Overall, this study provides a comprehensive strategy for AD metabolomics research, contributing to understanding the pathological mechanism of AD.
    Language English
    Publishing date 2022-05-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.904857
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Clinical study of anti-snake venom blockade in the treatment of local tissue necrosis caused by Chinese cobra (Naja atra) bites.

    Zeng, Linsheng / Hou, Jingjing / Ge, Cuihong / Li, Yanjun / Gao, Jianhua / Zhang, Congcong / Huang, Peiying / Du, Jiayu / Mo, Zhizhun / Liu, Yuxiang / Zeng, Zhongyi

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 12, Page(s) e0010997

    Abstract: Objective: This study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites.: Methods: Patients bitten by a Chinese cobra (Naja atra) (n = 50) ...

    Abstract Objective: This study aimed to evaluate the clinical therapeutic efficacy of anti-snake venom serum blockade in treating local tissue necrosis caused by Chinese cobra (Naja atra) bites.
    Methods: Patients bitten by a Chinese cobra (Naja atra) (n = 50) that met the inclusion criteria were randomly divided into two groups: the experimental group (n = 25) and the control group (n = 25). The experimental group received regular as well as anti-snake venom serum blocking treatment, whereas regular treatment plus chymotrypsin blocking therapy was given to the control group. The necrotic volumes around snake wounds in these groups were detected on the first, third and seventh days. On the third day of treatment, some local tissues in the wounds were randomly selected for pathological biopsy, and the necrosis volume of the local tissue was observed. Furthermore, the amount of time required for wound healing was recorded.
    Results: On the third and seventh days post-treatment, the necrotic volume of the wound of the experimental group was much smaller than that of the control group, and the experimental group's wound healing time was shorter than that of the control group (all p < 0.05). Moreover, the pathological biopsies taken from the control group showed nuclear pyknosis, fragmentation, sparse nuclear density, and blurred edges, and the degree of necrosis was much higher than that of the experimental group.
    Conclusions: Anti-snake venom blocking therapy is a new and improved therapy with good clinical effect on local tissue necrosis caused by Chinese cobra bites; moreover, it is superior to conventional chymotrypsin blocking therapy in the treatment of cobra bites. It can better neutralize and prevent the spread of the toxin, reduce tissue necrosis, and shorten the course of the disease by promoting healing of the wound. Furthermore, this treatment plan is also applicable to wound necrosis caused by other snake toxins, such as tissue necrosis caused by elapidae and viper families.
    Clinical trial registration: This trial is registered in the Chinese Clinical Trial Registry, a primary registry of International Clinical Trial Registry Platform, World Health Organization (Registration No. ChiCTR2200059070; trial URL:http://www.chictr.org.cn/edit.aspx?pid=134353&htm=4).
    MeSH term(s) Animals ; Humans ; Antivenins/therapeutic use ; Chymotrypsin/antagonists & inhibitors ; Elapid Venoms/toxicity ; Elapidae ; Naja naja ; Necrosis/drug therapy ; Snake Bites/drug therapy
    Chemical Substances Antivenins ; Chymotrypsin (EC 3.4.21.1) ; Elapid Venoms
    Language English
    Publishing date 2022-12-16
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010997
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Corrigendum: Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings.

    Xu, Zhibin / Tian, Ye / Li, A-Xiang / Tang, Jiahang / Jing, Xiao-Yuan / Deng, Chunshan / Mo, Zhizhun / Wang, Jiaxuan / Lai, Juan / Liu, Xuemei / Guo, Xuantong / Li, Tao / Li, Shupeng / Wang, Liping / Lu, Zhonghua / Chen, Zuxin / Liu, Xin-An

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 913285

    Abstract: This corrects the article DOI: 10.3389/fnmol.2022.800406.]. ...

    Abstract [This corrects the article DOI: 10.3389/fnmol.2022.800406.].
    Language English
    Publishing date 2022-05-12
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.913285
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings.

    Xu, Zhibin / Tian, Ye / Li, A-Xiang / Tang, Jiahang / Jing, Xiao-Yuan / Deng, Chunshan / Mo, Zhizhun / Wang, Jiaxuan / Lai, Juan / Liu, Xuemei / Guo, Xuantong / Li, Tao / Li, Shupeng / Wang, Liping / Lu, Zhonghua / Chen, Zuxin / Liu, Xin-An

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 800406

    Abstract: The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems ( ... ...

    Abstract The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5' monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.
    Language English
    Publishing date 2022-03-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.800406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Angelica sinensis Supercritical Fluid CO2 Extract Attenuates D-Galactose-Induced Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and Inflammation

    Mo, Zhi-Zhun / Chen, Jian-Ping / Huang, Shui-Qing / Li, Hui-Lin / Lin, Zhi-Xiu / Su, Zi-Ren / Xian, Yan-Fang / Xie, Jian-Hui / Yi, Tie-Gang / Zheng, Lin

    Journal of medicinal food. 2018 Sept. 01, v. 21, no. 9

    2018  

    Abstract: Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose ( ...

    Abstract Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that AS significantly improved liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.
    Keywords Angelica sinensis ; antioxidant enzymes ; brain ; carbon dioxide ; cognition ; copper ; cytokines ; galactose ; gene expression ; histology ; IKappaB kinase ; inducible nitric oxide synthase ; inflammation ; kidneys ; liver ; mice ; nerve tissue ; oxidative stress ; renal function ; superoxide dismutase ; toxicity
    Language English
    Dates of publication 2018-0901
    Size p. 887-898.
    Publishing place Mary Ann Liebert, Inc.
    Document type Article
    ZDB-ID 1427365-2
    ISSN 1557-7600 ; 1096-620X
    ISSN (online) 1557-7600
    ISSN 1096-620X
    DOI 10.1089/jmf.2017.4061
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Angelica sinensis Supercritical Fluid CO

    Mo, Zhi-Zhun / Lin, Zhi-Xiu / Su, Zi-Ren / Zheng, Lin / Li, Hui-Lin / Xie, Jian-Hui / Xian, Yan-Fang / Yi, Tie-Gang / Huang, Shui-Qing / Chen, Jian-Ping

    Journal of medicinal food

    2018  Volume 21, Issue 9, Page(s) 887–898

    Abstract: Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose ( ...

    Abstract Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that AS significantly improved liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.
    MeSH term(s) Angelica sinensis/chemistry ; Animals ; Chemical and Drug Induced Liver Injury/drug therapy ; Chemical and Drug Induced Liver Injury/metabolism ; Chromatography, Supercritical Fluid ; Drugs, Chinese Herbal/administration & dosage ; Drugs, Chinese Herbal/chemistry ; Drugs, Chinese Herbal/isolation & purification ; Galactose/adverse effects ; Humans ; Inflammation/drug therapy ; Inflammation/genetics ; Inflammation/metabolism ; Kidney/drug effects ; Kidney Diseases/chemically induced ; Kidney Diseases/drug therapy ; Kidney Diseases/metabolism ; Liver/drug effects ; Male ; Malondialdehyde/metabolism ; Mice ; Oxidative Stress/drug effects
    Chemical Substances Drugs, Chinese Herbal ; Malondialdehyde (4Y8F71G49Q) ; Galactose (X2RN3Q8DNE)
    Language English
    Publishing date 2018-08-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1427365-2
    ISSN 1557-7600 ; 1096-620X
    ISSN (online) 1557-7600
    ISSN 1096-620X
    DOI 10.1089/jmf.2017.4061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Andrographolide sodium bisulphite-induced inactivation of urease: inhibitory potency, kinetics and mechanism

    Mo, Zhi-Zhun / Wang, Xiu-Fen / Zhang, Xie / Su, Ji-Yan / Chen, Hai-Ming / Liu, Yu-Hong / Zhang, Zhen-Biao / Xie, Jian-Hui / Su, Zi-Ren

    BMC Complement Altern Med. 2015 Dec., v. 15, no. 1 p.238-238

    2015  

    Abstract: BACKGROUND: The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, ...

    Abstract BACKGROUND: The inhibitory effect of andrographolide sodium bisulphite (ASB) on jack bean urease (JBU) and Helicobacter pylori urease (HPU) was performed to elucidate the inhibitory potency, kinetics and mechanism of inhibition in 20 mM phosphate buffer, pH 7.0, 2 mM EDTA, 25 °C. METHODS: The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of ASB was characterized with IC₅₀ values. Lineweaver-Burk and Dixon plots for JBU inhibition of ASB was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni²⁺ binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. RESULTS: The IC₅₀ of ASB against JBU and HPU was 3.28 ± 0.13 mM and 3.17 ± 0.34 mM, respectively. The inhibition proved to be competitive and concentration- dependent in a slow-binding progress. The rapid formation of initial ASB-JBU complex with an inhibition constant of K ᵢ = 2.86 × 10⁻³ mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K ᵢ * = 1.33 × 10⁻⁴ mM. The protective experiment proved that the urease active site is involved in the binding of ASB. Thiol reagents (L-cysteine and dithiothreithol) strongly protect the enzyme from the loss of enzymatic activity, while boric acid and fluoride show weaker protection, indicating that the active-site sulfhydryl group of JBU was potentially involved in the blocking process. Moreover, inhibition of ASB proved to be reversible since ASB-inactivated JBU could be reactivated by dithiothreitol application. Molecular docking assay suggested that ASB made contacts with the important sulfhydryl group Cys-592 residue and restricted the mobility of the active-site flap. CONCLUSIONS: ASB was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for the treatment of urease-related diseases.
    Keywords Canavalia ensiformis ; Helicobacter pylori ; active sites ; ammonia ; andrographolide ; boric acid ; complement ; cysteine ; dithiothreitol ; enzyme activity ; fluorides ; isomerization ; pH ; phosphates ; sodium ; sodium bisulfite ; thiols ; urease ; urease inhibitors
    Language English
    Dates of publication 2015-12
    Size p. 238.
    Publishing place BioMed Central
    Document type Article ; Online
    ZDB-ID 2050429-9
    ISSN 1472-6882
    ISSN 1472-6882
    DOI 10.1186/s12906-015-0775-4
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  10. Article ; Online: Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism.

    Zhou, Jiang-Tao / Li, Cai-Lan / Tan, Li-Hua / Xu, Yi-Fei / Liu, Yu-Hong / Mo, Zhi-Zhun / Dou, Yao-Xing / Su, Rui / Su, Zi-Ren / Huang, Ping / Xie, Jian-Hui

    PloS one

    2017  Volume 12, Issue 1, Page(s) e0168944

    Abstract: In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted ... ...

    Abstract In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/mL under neutral environment (pH 7.4), and from 75 to 100 μg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Berberine Alkaloids/pharmacology ; Catalytic Domain ; Coptis/chemistry ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal/pharmacology ; Gastrointestinal Diseases/drug therapy ; Helicobacter Infections/drug therapy ; Helicobacter pylori/drug effects ; Helicobacter pylori/enzymology ; Humans ; Hydrogen-Ion Concentration ; Inhibitory Concentration 50 ; Microbial Sensitivity Tests ; Molecular Docking Simulation ; Nickel/chemistry ; Plant Extracts/metabolism ; Species Specificity ; Sulfhydryl Compounds/chemistry ; Urease/antagonists & inhibitors ; Urease/metabolism
    Chemical Substances Anti-Bacterial Agents ; Berberine Alkaloids ; Drugs, Chinese Herbal ; Plant Extracts ; Sulfhydryl Compounds ; Nickel (7OV03QG267) ; Urease (EC 3.5.1.5) ; palmatine (G50C034217)
    Language English
    Publishing date 2017-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0168944
    Database MEDical Literature Analysis and Retrieval System OnLINE

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