Sanguinarine, a major alkaloid from Zanthoxylum nitidum (Roxb.) DC., inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism.

Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicine and mainly adopted to treat gastric ulcer, gastritis and stomach cancer. Sanguinarine (SNG), a natural alkaloid isolated from Z. nitidum , possesses significant anti- Helicobacter pylori and gastric protection effects. Ho...

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Publicado en:Journal of Ethnopharmacology Vol. 295
Autores principales: Lu, Qiang, Zhang, Zhenshan, Xu, Yifei, Chen, Yujia, Li, Cailan
Formato: research Journal Article
Publicado: Elsevier B.V. Sep2022
Acceso en línea:Ver este registro en EBSCOhost
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        03788741
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      jtl: Journal of Ethnopharmacology
      issn: 03788741
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      dt: Sep2022
      vid: 295
      pid: 1004
      pub: Elsevier B.V.
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        158013615
        158013615
        158013615
        10.1016/j.jep.2022.115388
        158013615
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        atl: Sanguinarine, a major alkaloid from Zanthoxylum nitidum (Roxb.) DC., inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism.
      aug:
        au:
          Lu, Qiang
          Zhang, Zhenshan
          Xu, Yifei
          Chen, Yujia
          Li, Cailan
        affil: Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China
      sug:
        subj:
          Alkaloids Pharmacodynamics
          Alkaloids Pharmacokinetics
          Microbial Culture and Sensitivity Tests Evaluation
          Urease Drug Effects
          Helicobacter Pylori Drug Effects
          Legumes Drug Effects
          Plants, Medicinal Pharmacodynamics
          Human
          Spectrophotometry
          Glutathione Pharmacodynamics
          Alkaloids Administration and Dosage
          Toxicity Tests
          Enzyme Inhibitors Pharmacodynamics
          Boric Acids Pharmacodynamics
          Sodium Compounds Pharmacodynamics
          Sulfhydryl Reagents Pharmacodynamics
          Alkaloids Physiology
      ab: Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicine and mainly adopted to treat gastric ulcer, gastritis and stomach cancer. Sanguinarine (SNG), a natural alkaloid isolated from Z. nitidum , possesses significant anti- Helicobacter pylori and gastric protection effects. However, the underlying mechanism is sparsely elucidated. The present study aims to explore the inhibition effect, kinetics and potential mechanism of SNG against H. pylori urease (HPU) and jack bean urease (JBU). The improved spectrophotometric berthelot method was applied to estimate the inhibitory effect of SNG against HPU and JBU. The Lineweaver-Burk plots were adopted for investigating the inhibitory pattern in enzymatic kinetics. Sulfydryl-containing compounds and competitive active-site Ni2+ binding depressors were used for mechanism research. SNG remarkably suppressed the activities of HPU and JBU in concentration-and time-dependent mode with IC 50 of 0.48 ± 0.14 mM and 0.11 ± 0.02 mM, respectively, in comparison with urease retardant acetohydroxamic acid (0.06 ± 0.01 mM for HPU and 0.03 ± 0.00 mM for JBU, respectively). Kinetic analysis demonstrated that the inhibition of SNG against HPU and JBU were separately characterized by slow-binding, mixed-type and slow-binding, non-competitive type. Addition of sulfydryl-containing reagents (dithiothreitol, glutathione and L-cysteine) and competitive Ni2+ binding restrainers (boric acid and sodium fluoride) significantly abrogated the urease inhibitory effect of SNG, suggesting the significant role of the thiols and Ni2+ for the urease inhibition by SNG. By contrast, interaction with thiol groups possibly contributed to the repression of SNG on JBU. Furthermore, the urease suppression was proved to be partially reversible since the SNG-blocked enzyme could be partly reactivated by glutathione. SNG could observably inhibit H. pylori urease targeting the thiols and Ni2+, which indicated that SNG was a new urease suppressant with great promise. The present research also provided scientific evidence for the application of SNG and Z. nitidum treating H. pylori -associated gastrointestinal diseases. [Display omitted]
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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