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Insight into the inhibitory effects of Zanthoxylum nitidum against Helicobacter pylori urease and jack bean urease: Kinetics and mechanism.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2020 Mar 01; Vol. 249, pp. 112419. Date of Electronic Publication: 2019 Nov 20. - Publication Year :
- 2020
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Abstract
- Ethnopharmacological Relevance: 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.<br />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.<br />Materials and Methods: 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 Ni <superscript>2+</superscript> -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.<br />Results: 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 <subscript>50</subscript>  = 1.29 ± 0.10 mg/mL) than on JBU (IC <subscript>50</subscript>  = 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 Ni <superscript>2+</superscript> . Results indicated that these components are potential active ingredients directed against urease.<br />Conclusions: 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.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Anti-Bacterial Agents isolation & purification
Anti-Bacterial Agents therapeutic use
Bacterial Proteins antagonists & inhibitors
Bacterial Proteins chemistry
Bacterial Proteins metabolism
Canavalia enzymology
Drugs, Chinese Herbal isolation & purification
Drugs, Chinese Herbal therapeutic use
Enzyme Assays
Helicobacter Infections drug therapy
Helicobacter Infections microbiology
Helicobacter pylori enzymology
Humans
Molecular Docking Simulation
Plant Proteins antagonists & inhibitors
Plant Proteins chemistry
Plant Proteins metabolism
Plant Roots chemistry
Stomach Diseases drug therapy
Stomach Diseases microbiology
Urease chemistry
Urease metabolism
Anti-Bacterial Agents pharmacology
Drugs, Chinese Herbal pharmacology
Helicobacter pylori drug effects
Urease antagonists & inhibitors
Zanthoxylum chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 249
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31759110
- Full Text :
- https://doi.org/10.1016/j.jep.2019.112419