Insight into the inhibitory effects of Zanthoxylum nitidum against Helicobacter pylori urease and jack bean urease: Kinetics and mechanism.
Zanthoxylum nitidum (Roxb.) DC. is a traditional Chinese medicine characterised by anti-inflammatory and anti- Helicobacter pylori , which is widely used to treat H. pylori- induced gastric disease in China. However, the underlying mechanism related to its anti- H. pylori activity remains unclear. U...
| Publicado en: | Journal of Ethnopharmacology Vol. 249 |
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| Autores principales: | , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Elsevier B.V.
Mar2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=140848613&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 140848613 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03788741 3MS jtl: Journal of Ethnopharmacology issn: 03788741 maglogo: N pubinfo: dt: Mar2020 vid: 249 pid: 1004 pub: Elsevier B.V. artinfo: ui: 140848613 140848613 140848613 10.1016/j.jep.2019.112419 140848613 ppct: 1 formats: tig: atl: Insight into the inhibitory effects of Zanthoxylum nitidum against Helicobacter pylori urease and jack bean urease: Kinetics and mechanism. aug: au: Lu, Qiang Li, Cailan Wu, Guosong affil: Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China sug: subj: Medicine, Chinese Traditional Plant Extracts Pharmacodynamics Helicobacter Pylori Drug Effects Urease Drug Effects Plant Extracts Pharmacokinetics Plant Roots Human Chromatography Methods Sulfhydryl Reagents Nickel Antagonists and Inhibitors Enzymes Drug Effects Stomach Diseases Drug Therapy Treatment Outcomes ab: Zanthoxylum nitidum (Roxb.) DC. is a traditional Chinese medicine characterised by anti-inflammatory and anti- Helicobacter pylori , which is widely used to treat H. pylori- induced gastric disease in China. However, the underlying mechanism related to its anti- H. pylori activity remains unclear. Urease plays a crucial role in the colonisation and survival of H. pylori. Aim of the study : The root aqueous extract of Z. nitidum against H. pylori urease (HPU) and jack bean urease (JBU) was investigated to illuminate the inhibitory potency, kinetics and potential mechanism. Z. nitidum components were determined by UPLC. The enzyme inhibitory effects of Z. nitidum were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. Urease inhibition kinetics were determined by Lineweaver-Burk plots. Sulfhydryl group reagents and Ni2+-binding inhibitors were used in the mechanism study. Moreover, the molecular docking technique was used to investigate the binding conformations of the main compounds of Z. nitidum on Urease. According to UPLC results, the major components of Z. nitidum were magnoflorine, sanguinarine, nitidine chloride, chelerythrine, skimmianine and L-Sesamin. Z. nitidum has higher enzyme inhibitory activity on HPU (IC 50 = 1.29 ± 0.10 mg/mL) than on JBU (IC 50 = 2.04 ± 0.27 mg/mL). Enzyme inhibitory kinetic analysis revealed that the type of Z. nitidum inhibition against HPU was a slow-binding and mixed-type, whereas a slow-binding and non-competitive type inhibited JBU. Further mechanism study indicated that the active site of sulfhydryl group might be the target of inhibition by Z. nitidum. The molecular docking study indicated that the above six main components of Z. nitidum exhibited stronger affinity to HPU than to JBU through interacting with the key amino acid residues located on the mobile flap or interacting with the active site Ni2+. Results indicated that these components are potential active ingredients directed against urease. Z. nitidum inactivated urease in a concentration-dependent manner through slow-binding inhibition and binding to the urease active site sulfhydryl group. Our investigation might provide experimental evidence for the traditional application of Z. nitidum in the treatment of H. pylori -associated gastric disorders. Image 1 pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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