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

文献类型： 外文期刊

第一作者： Lu, Qiang

作者： Lu, Qiang;Chen, Yujia;Zhang, Zhenshan;Xu, Yifei;Li, Cailan;Li, Cailan

作者机构：

关键词： Sanguinarine; Zanthoxylum nitidum; Helicobacter pylori urease; Jack bean urease; Inhibitor; Mechanism

期刊名称：JOURNAL OF ETHNOPHARMACOLOGY （ 影响因子：5.195； 五年影响因子：5.242 ）

ISSN： 0378-8741

年卷期： 2022 年 295 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: 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. Aim of this study: 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). Materials and methods: 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. Results: SNG remarkably suppressed the activities of HPU and JBU in concentration-and time-dependent mode with IC50 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. Conclusion: 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.

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