JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2018
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IF 3.638
Cailan Li,Ping Huang,Kambo Wong,Yifei Xu,Lihua Tan,Hanbin Chen,Qiang Lu,Chaodan Luo,Chunlai Tam,Lixiang Zhu,Ziren Su,Jianhui Xie
In this study, we examined the anti-Helicobactor pylori effects of the main protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying antibacterial and bactericidal effects against three standard H. pylori strains and eleven clinical isolates, including four drug-resistant strains, with minimum inhibitory concentrations ranging from 25 to 50 μg/mL and minimal bactericidal concentrations ranging from 37.5 to 125 μg/mL. Coptisine’s anti-H. pylori effects derived from specific inhibition of urease in vivo. In vitro, coptisine inactivated urease in a concentration-dependent manner through slow-binding inhibition and involved binding to the urease active site sulfhydryl group. Coptisine inhibition of H. pylori urease (HPU) was mixed type, while inhibition of jack bean urease was non-competitive. Importantly, coptisine also inhibited HPU by binding to its nickel metallocentre. Besides, coptisine interfered with urease maturation by inhibiting activity of prototypical urease accessory protein UreG and formation of UreG dimers and by promoting dissociation of nickel from UreG dimers. These findings demonstrate that coptisine inhibits urease activity by targeting its active site and inhibiting its maturation, thereby effectively inhibiting H. pylori. Coptisine may thus be an effective anti-H. pylori agent.
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MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 10
·1-10
·
IF 5.3
Wang Yuhan,Zhang Ping,Zhou Chuxian,Zheng Zicong,Quan Qiang,He Guangbo,Zhai Hening,Song Qifang,Zhang Xiaoli,Li Heng,Peng Lanhuan,Liao Yuqin,Fang Wei,Li Minmin,Liang Jiajie,Tang Yong
Helicobacter pylori ( H. pylori ) is a major pathogen associated with gastric ulcers and gastric cancer, infecting approximately half of the global population. Therefore, developing sensitive, rapid, and cost-effective detection methods for H. pylori is critical for public health. We developed an innovative microscale colorimetric microsensor integrated with smartphone ambient-light sensors for portable, on-site quantification of H. pylori- associated urease activity in dental plaque. This low-cost device (< $ 5 fabrication) employs 3D-printed components and a custom app to measure transmittance changes from urease-catalyzed urea hydrolysis with phenol red, achieving a robust correlation with commercial microplate reader absorbance ( R 2 = 0.9989). The system demonstrates exceptional Analytical sensitivity, with limits of detection of 9.75 U/L for urease And 1.709 × 10 3 CFU/mL for H. pylori , alongside high reproducibility (CV < 10%) And stability over 14 days. When applied to the on-site detection of dental plaque among volunteers, the smartphone-based colorimetric microsensor exhibited detection results that were highly aligned with H. pylori infections confirmed by the urea breath test. It outperformed commercial test strips And achieved 100% sensitivity, 95.5% specificity, And 97.1% accuracy. This miniaturized, smartphone-based platform offers a promising solution for home self-testing and demonstrates significant potential for enhancing H. pylori preliminary screening at the community level.
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PHARMACEUTICAL CHEMISTRY JOURNAL
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2024
·Vol. 57
·期 8
·1179-1188
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IF 0.8
Pan Miao,Yuan Jia,Tang Qin,Wu Yajing,Peng Yu,Zhang Jinyin,Ma Hang,Li Xuegang
Antibiotic resistance is a major problem in the treatment of Helicobacter pylori (H. pylori). Berberine (BBR) has proven to be a promising alternative, though it is less effective than antibiotics. Structurally modified BBR might improve the anti-H. pylori activity. In this study, 8-octyl berberine (OBBR), a BBR derivative, was investigated for the activity and mechanism of action against H. pylori. The results showed that the anti-H. pylori activity of OBBR was significantly higher than that of BBR (about 64 times) and close to amoxicillin. Surprisingly, OBBR was not resistant to H. pylori after 45 generations of induction and showed synergistic effect with amoxicillin in vitro. Regarding the mechanism, OBBR changed the morphological structure of bacteria and caused the outgrowth of phosphatidylserine on the cell membrane, thereby increasing its permeability. Moreover, OBBR inhibited the urease activity, down-regulated the mRNA levels of flagellar genes flaA and flaB, and reduced the motility of H. pylori, thus inhibiting intra-gastric colonization. In an animal model of H. pylori infection, OBBR was found to have a certain effect on the clearance of H. pylori in mice. An excellent anti-H. pylori activity and low drug resistance of OBBR suggest that structural modification of the BBR scaffold may be a favorable approach to the development of promising antibiotics for the treatment of H. pylori.
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BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Chao Du,Zhen Zhang,Wenli Qiao,Leina Jia,Furui Zhang,Mengjun Chang,Xinsheng Liu,Le Guo,Yonghong Li
The epitope vaccine against four virulence proteins (FVpE) from Helicobacter pylori (H. pylori) was expressed and purified. Western blot and Enzyme-linked Immunosorbent Assays (ELISA) were used to identify and investigate the immunoreactivity of FVpE protein. The immune-sensing platform based on titanium carbide/colloidal gold nanoparticles@carbon nanofiber/ionic liquid composites electrode was constructed for immobilizing FVpE. Electrochemical impedance spectroscopy (EIS) was used to study the electrochemical properties of the modified electrodes . The relevant influenced factors were optimized including pH value, antigen concentration, and incubating time. The prepared H. pylori label-free electrochemical immunosensor was used for antibody detection using differential pulse voltammetry (DPV). Under the optimal experimental conditions, the linear ranges of H. pylori antibodies, including anti- H. pylori , cytotoxin-associated gene A (CagA), vacuolating cytotoxin-associated gene A (VacA), and urease A (UreA), were all 0.1–5 ng mL −1 , except urease B (UreB, 0.1–4.5 ng mL −1 ). The selectivity study showed that other antibodies had little influence on the detection of H. pylori antibodies. The immunosensor could be used to detect serum samples, and the recoveries were in the range of 68.5%–100.5%.
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Pharmaceutics
·
2024
·Vol. 16
·期 10
·1242
·
IF 4.9
Da Hun Kim,Sa-Won Lee,Jun Hak Lee,Jin Woo Park,Sung Mo Park,Han-Joo Maeng,Tae-Sung Koo,Kwan Hyung Cho
Background/Objectives:The aim of this work was to prepare and characterize gastroretentive floating combination tablets (GRCTs) containing 500 mg of amoxicillin trihydrate (AMX) and 125 mg of levofloxacin (LVX) that provide sustained drug release and stability at gastric pH levels for the eradication of resistantHelicobacter pylori.Method:GRCTs were prepared with low-density excipients and hydrophilic swellable polymers, including hydroxypropyl methylcellulose (HPMC) of various viscosities, polyethylene oxide (PEO), and carboxymethylcellulose (CMC), by the direct compression method. The prepared GRCTs were investigated and optimized in terms of pH stability, tablet hardness, floating lag time and total floating time, drug release rate, gel strength.Results:AMX and LVX in GRCT were stable at the HP eradication target pH above 4.0. The effervescent GRCT composition (AMX/LVX/HPMC [4000 cP]/CMC/microcrystalline cellulose/citric acid/sodium bicarbonate/calcium silicate/silicon dioxide/magnesium stearate = 500/125/50/50/125/40/60/30/10/10,w/w) yielded acceptable hardness (>6 kp), reduced floating lag time (<5 s), a long floating duration (>12 h), and sustained release rates of AMX and LVX (>90% until 12 h). This optimized GRCT had a gel strength of 107.33 ± 10.69 g and pH > 4.0, which maintained the tablets’ shape and AMX stability for 12 h.Conclusions:Collectively, the formulated effervescent GRCTs combining AMX and LVX represented a promising candidate dosage form for eradicating resistantH. pylori.
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BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Huina Sun,Wei Jin,Handong Yao,Mingshi Deng,Xuefeng Wang,Xinghua Gao,Wanyin Xu,Qianqian Li,Yongheng Zhu,Ning Zhao,Yuan Zhang
Helicobacter pylori (H. pylori) is a prevalent bacterium that infects the stomach, can cause numerous gastric diseases, and potentially result in stomach cancer. Current H. pylori detection methods have various limitations; thus, to streamline H. pylori detection, we developed an electrochemical microsensor featuring Ni-based atom cluster (AC)/oxide nanocomposite catalysts for direct biomarker identification. By incorporating Ni ACs and transforming Ni oxides into an ultrathin, porous structure, the resulting material exhibited excellent electrocatalytic activity. In particular, it enabled the detection of urease, a biomarker specific to H. pylori , at concentrations as low as 10 ng/mL. The fabricated Ni AC/NiO@laser-etched graphene (LEG) electrochemical microsensor demonstrated excellent sensitivity and specificity in detecting urease within the concentration range of 10–100 ng/mL. Moreover, its accuracy in analyzing clinical samples matched that of commercial enzyme-linked immunosorbent assay kits, highlighting its potential as a platform for both the personal health monitoring and clinical diagnosis of H. pylori infection. This microsensor exhibited excellent sensitivity and precision and rapid recognition with intuitive operation and ease of use. It holds considerable promise in enhancing and improving medical diagnostics by providing timely and accurate information, enabling earlier interventions, and improving patient outcomes.
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HELICOBACTER
·
2023
·
IF 4.4
Zelin Zhang,Xingchi Chen,Bin Li,Tingting Xia,Xiaobin Wu,Chao Wu
Background Urease subunit B (UreB), a conserved and key virulence factor of Helicobacter pylori ( H. pylori ), can induce the host CD4 + T cell immune responses to provide protection, but less is known regarding CD8 + T cell responses. The characteristics of H. pylori -specific CD8 + T cell responses and the mechanism underlying antigen processing and presentation pathways remain unclear. This study was focus on protective antigen recombinant UreB (rUreb) to detect specific CD8 + T cell responses in vitro and elucidate the mechanism of UreB antigen processing and presentation. Methods The peripheral blood mononuclear cells (PBMCs) collected from H. pylori -infected individuals were stimulated with rUreB in vitro to detect specific CD8 + T cell responses after co-culture with rUreB-pulsed autologous hMDCs. Through blocking assay, we investigated the potential pathway of UreB antigen processing and presentation via the cytosolic pathway or vacuolar pathway. The cytokines production of UreB specific CD8 + T cell were evaluated as well. Results We demonstrated UreB can induce specific CD8 + T cell immune responses in H. pylori infected individuals. Importantly, we characterized that UreB were mainly processed by proteasome instead of lysosomal proteases and presented through cytosolic pathway of cross-presentation, which requires endoplasmic reticulum–Golgi transport and newly synthesized MHC-I molecules, to induce functional-specific CD8 + T cell (IFN-γ + TNF-α + Grz A+ Grz B+) responses. Conclusions These results suggest that H. pylori UreB induces specific CD8 + T cell responses through cytosolic pathway of cross-presentation in infected individuals.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaoyi Zheng,Yijie Xie,Linlin Zhao,Xiaojuan Huang,Shige Wang,Yongkang Lai,Peng Fan,Yanbo Zeng,Jiulong Zhao,Zhaoshen Li
This study developed a chitosan (CS)‑sodium tripolyphosphate (TPP)‑zinc (Zn) nanogel for treating Helicobacter pylori ( H. pylori ) through synergistic antibacterial, anti-inflammatory, and mucosal repair mechanisms. The nanogel was synthesized via an emulsion method, leveraging electrostatic interactions between CS amino groups and TPP phosphate ions, followed by Zn incorporation. Characterization revealed uniform spherical nanoparticles (~200 nm) with high Zn content (20.18 %) and controlled hydrogen (H 2 ) and Zn 2+ release (15 h) in acidic environments. In vitro assays demonstrated potent antibacterial activity against H. pylori (95.83 % inhibition at pH = 2; 28.54 % inhibition at pH = 7) attributed to Zn 2+ -mediated enzyme disruption. The nanogel exhibited significant antioxidant capacity, scavenging 82.3 % of PTIO and 65.48 % of DPPH radicals. Biocompatibility testing confirmed minimal haemolysis (<5 %) and high cell viability (>95 %). In vivo studies in H. pylori -infected mice demonstrated a bacterial inhibition rate of 97.54 % through upregulation of β-catenin and tight junction proteins. Concurrently, mucosal repair was enhanced, achieving migration rates of 44.2 ± 5.6 % and 72.34 ± 2.1 % at 12 and 24 h respectively. The nanogel also preserved gut microbiota diversity post-treatment, unlike conventional antibiotics. This multifunctional nanogel platform combines biocompatibility, ease of manufacture and dual therapeutic effects. In summary, this study proposes a multifunctional therapeutic strategy capable of simultaneously addressing H. pylori infection, gastric inflammation and mucosal damage. It offers a paradigm shift from traditional antibiotic-centred therapies, providing a promising strategy for eradicating Helicobacter pylori and restoring gastric injury.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ling Ou,Heng-rui Liu,Xiao-yan Shi,Chang Peng,Yuan-jing Zou,Jun-wei Jia,Hui Li,Zhi-xiang Zhu,Yan-hua Wang,Bing-mei Su,Yu-qian Lai,Mei-yun Chen,Wei-xing Zhu,Zhong Feng,Gui-min Zhang,Mei-cun Yao
Ethnopharmacological relevance Terminalia chebula Retz. , known as the King of Traditional Tibetan Medicine, is widely used for treating various ailments, particularly stomach disorders . It exhibited inhibitory activity against helicobacter pylori . Aim of the study : The exact mechanism by which T. chebula combats H. pylori infection remains unclear. Therefore, this study aimed to investigate its mechanism of action and the key pathways and targets involved. Material and methods Minimum inhibitory concentration (MIC) assay, scanning electron microscope, and inhibiting kinetics curves were conducted. The mRNA expressions were measured by RNA-seq analysis and RT-QPCR. ELISA and Western blot were used to detect the changes in proteins. The main compounds were analyzed by High-performance Liquid Chromatography. The interaction between the compound and target was predicted by Molecular Docking. Results The study revealed that T. chebula disrupted the structure of H. pylori bacteria and inhibited Cag A protein expression. Additionally, T. chebula can reduce the expression of flaA, flaB , babA, alpA, alpB, ureE, and ureF genes. Furthermore, T. chebula demonstrated its effectiveness in inhibiting the H. pylori -induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway. Moreover, the study discovered that chebulagic acid has anti-HP activity and inhibits the expression of Cag A protein. Conclusions T. chebula acts as a natural remedy for combating H. pylori infection. Its ability to disrupt the bacterial structure, inhibit key proteins, regulate inflammatory pathways, and the presence of chebulagic acid contribute to its anti- H. pylori activity.
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MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Xiaojie Song,Man-Man Lv,Qi-Yan Lv,Hui-Fang Cui,Jing Fu,Yu-Yang Huo
A novel and sensitive Helicobacter pylori assay strategy based on linear isothermal amplification reaction (LIAR) and DNAzymes catalyzed DNA sensor was developed. A 17 nt target DNA (tDNA) specific in the H. pylori genome was selected and used as primer in the LIAR. A template DNA was designed to produce an amplicon with Mg 2+ -dependent and RNA-cleaving DNAzyme (Md-Dz) activity. The amplicon (i.e. Md-Dz) was then detected with the DNA sensor. The DNA sensor was fabricated simply through immobilization of a hairpin DNA that contains both Md-Dz substrate and G-quadruplex DNAzyme (Gq-Dz), on gold electrodes. The Gq-Dz possesses peroxidase activity, catalyzing the electro-redox of the electrochemical signal probe hydroquinon. The LIAR, Md-Dz catalytic reaction, and DNA sensor fabrication and detection processes were characterized and optimized. The LIAR amplification efficiency is as high as ~5 × 10 5 fold, and the assay strategy is very sensitive, selective and repetitive. The differential pulse voltammetry (DPV) detection signals linearly correlate to the logarithmic tDNA concentration in the range of 0.1–10,000 fM, with a limit of detection (LOD) of 34 aM. The detection linear range for H. pylori genomic DNA is 2.1–67.2 pg, with an LOD of 1.3 pg . Muted DNA sequences and other pathogenic bacteria did not result in interferences. In addition, the DNA sensor is very stable in storage. More importantly, the DNA sensor and the assay strategy could be universally applicable to detect any biological sample and short DNA sequence of interests.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Haoyu Qiu,Lisha Gong,Paul Slezak,Shixiong He,Fei Lu,Kun Yu,Jing Xie,Zhen Geng,Enling Hu,Zhihang Zhou,Guangqian Lan,Ruiqi Xie
The Helicobacter pylori infection in the stomach is the key reason for gastric mucosal bleeding. Eliminating gastric Helicobacter pylori by oral treatment remains difficult due to the presence of the gastric mucosal layer, which acts as a physical barrier to drugs via oral administration. In this study, a magnetic-navigable microneedle drug delivery platform (MNs D) for oral administration, featuring differential dual-mode drug release rate, was designed to fulfil rapid gastric hemostasis and overcome the gastric barriers for long-lasting Helicobacter pylori inhibition in stomach. MNs-D was created by rationally loading the carrier substrate, which was composed of silk fibroin with variable solubility, with antibiotics and hemostats. In vitro experiments showed MNs-D may sustainably eradicate Helicobacter pylori in stimulated gastric juices with long-lasting drug release (79 % in 24 h) and quickly establish hemostasis with instant drug release (92 % within 60 s). Most importantly, in vivo studies demonstrated MNs-D overcame the unsettling gastric mucosal barrier in traditional therapies of oral administration by insertion into the GML under magnetic navigation, resulting in sustained antibiotic release for long-lasting Helicobacter pylori eradiation (99 %). For differential dual-mode medication release against gastric Helicobacter pylori infections, this study may have firstly examined the effects of magnetic navigated microneedles administered orally.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 16
·7791
·
IF 4.9
Shuling He,Lvyun Sun,Jiali Chen,Yixin Li,Ying Pan,Amei Su,Qiuyao Mao,Jiaqian Hu,Disheng Feng,Yang Ouyang
Sulforaphane, a natural isothiocyanate predominantly found in cruciferous vegetables, has shown potential in preventing and treating Helicobacter pylori infection. However, the underlying metabolic mechanisms remain largely unclear. This study employed high-coverage metabolomics and lipidomics methods to comprehensively investigate the effects of sulforaphane on the serum and liver metabolic profiles of H. pylori -infected mice. Metabolomics and lipidomics analysis revealed that H. pylori infection disrupted multiple metabolic pathways, leading to perturbations in amino acids, fatty acids, bile acids, and various lipid species. Sulforaphane treatment can ameliorate these disruptions, notably reversing alterations in serum glycerophospholipids and restoring hepatic levels of amino acids, bile acids, glycerophospholipids, ceramides, and peptides. Key metabolic pathways implicated included glutathione metabolism and glycine and serine metabolism, which are associated with antioxidant defense and host resistance to pathogenic infections. These findings offer a comprehensive metabolic basis for understanding the therapeutic effects of sulforaphane against H. pylori infection.
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