Biomaterial Database

Sanguinarine, a major alkaloid from Zanthoxylum nitidum (Roxb.) DC., inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism. 2022

Qiang Lu, and Zhenshan Zhang, and Yifei Xu, and Yujia Chen, and Cailan Li

Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China.

BACKGROUND 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. OBJECTIVE 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). 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. CONCLUSIONS 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.

UI	MeSH Term	Description	Entries
D007546	Isoquinolines	A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000470	Alkaloids	Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)	Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
D013438	Sulfhydryl Compounds	Compounds containing the -SH radical.	Mercaptan,Mercapto Compounds,Sulfhydryl Compound,Thiol,Thiols,Mercaptans,Compound, Sulfhydryl,Compounds, Mercapto,Compounds, Sulfhydryl
D014510	Urease	An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5.	Phytourease,Urea Amidohydrolase,Amidohydrolase, Urea
D016480	Helicobacter pylori	A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405).	Campylobacter pylori,Campylobacter pylori subsp. pylori,Campylobacter pyloridis,Helicobacter nemestrinae
D053119	Benzophenanthridines	Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.
D032106	Zanthoxylum	A plant genus of the family RUTACEAE. Some members of Zanthoxylum are reclassified from ELEUTHEROCOCCUS, Melicope, and EVODIA. The twigs are used as dental brushing sticks (TOOTHBRUSHING). Most plants that are called Fagara have been reclassified as Zanthoxylum, however some Fagara were reclassified to MELICOPE (also in the Rutacea family) or to GLEDITSIA (a genus in the FABACEAE family).	Xanthoxylum,Fagara ailanthoides,Fagara boninensis,Fagara coco,Fagara cuspidata,Fagara heitzii,Fagara leprieurii,Fagara macrophylla,Fagara mayu,Fagara monophyllum,Fagara nitidum,Fagara rhetza,Fagara rubescens,Fagara tessmannii,Fagara xanthoxyloides,Fagara zanthoxyloides,Xanthoxylum cuspidatum,Xanthoxylum inerme,Zanthoxylum ailanthoides,Zanthoxylum coco,Zanthoxylum fagara,Zanthoxylum gilletii,Zanthoxylum heitzii,Zanthoxylum leprieurii,Zanthoxylum mayu,Zanthoxylum monophyllum,Zanthoxylum nitidum,Zanthoxylum rhetza,Zanthoxylum rubescens,Fagara ailanthoide,Fagara boninenses,Fagara cocos,Fagara cuspidatas,Fagara heitzius,Fagara leprieurius,Fagara macrophyllas,Fagara mayus,Fagara monophyllums,Fagara nitidums,Fagara rhetzas,Fagara rubescen,Fagara tessmannius,Fagara xanthoxyloide,Fagara zanthoxyloide,Xanthoxylum cuspidatums,Xanthoxylum inermes,Xanthoxylums,Zanthoxylum ailanthoide,Zanthoxylum cocos,Zanthoxylum fagaras,Zanthoxylum gilletius,Zanthoxylum heitzius,Zanthoxylum leprieurius,Zanthoxylum mayus,Zanthoxylum monophyllums,Zanthoxylum nitidums,Zanthoxylum rhetzas,Zanthoxylum rubescen,Zanthoxylums,ailanthoide, Fagara,ailanthoide, Zanthoxylum,ailanthoides, Fagara,ailanthoides, Zanthoxylum,boninenses, Fagara,coco, Fagara,coco, Zanthoxylum,cocos, Fagara,cocos, Zanthoxylum,cuspidata, Fagara,cuspidatas, Fagara,cuspidatum, Xanthoxylum,cuspidatums, Xanthoxylum,fagaras, Zanthoxylum,gilletii, Zanthoxylum,gilletius, Zanthoxylum,heitzii, Fagara,heitzii, Zanthoxylum,heitzius, Fagara,heitzius, Zanthoxylum,inerme, Xanthoxylum,leprieurii, Fagara,leprieurii, Zanthoxylum,leprieurius, Fagara,leprieurius, Zanthoxylum,macrophylla, Fagara,macrophyllas, Fagara,mayu, Fagara,mayu, Zanthoxylum,mayus, Fagara,mayus, Zanthoxylum,monophyllum, Fagara,monophyllum, Zanthoxylum,monophyllums, Fagara,monophyllums, Zanthoxylum,nitidum, Fagara,nitidum, Zanthoxylum,nitidums, Fagara,nitidums, Zanthoxylum,rhetza, Fagara,rhetza, Zanthoxylum,rubescen, Fagara,rubescen, Zanthoxylum,rubescens, Fagara,rubescens, Zanthoxylum,tessmannii, Fagara,tessmannius, Fagara,xanthoxyloides, Fagara,zanthoxyloides, Fagara
D032449	Canavalia	A plant genus of the family FABACEAE. Canavalia ensiformis is the source of CONCANAVALIN A.	Canavalias