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Background: The aqueous extract of the dried buds of Syzygium aromaticum (SAAE) have the potential to alleviate Helicobacter pylori infection, but the specific molecular mechanism has not been fully elucidated., Purpose: This study aimed to investigate the underlying mechanisms of SAAE on H. pylori pathogenicity., Methods: The inhibitory kinetics and anti-H. pylori adhesive capacity assays were conducted to examine the effects of SAAE on the growth and adhesive capability of H. pylori. The H. pylori outer membrane vesicles (OMVs) were purified from the culture supernatant through high-speed centrifugation, filtration, and two rounds of ultracentrifugation. Their characteristics and protein composition were then identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and qualitative proteomics study. Subsequently, the effect of SAAE on the pathogenicity of H. pylori OMVs was investigated using the Griess reagent assay, enzyme-linked immunosorbent assay (ELISA), quantitative proteomics study, TEM, and western blotting assay., Results: SAAE exhibited inhibitory effects on H. pylori growth and adhesion. The isolated H. pylori OMVs showed particle size of 27-242 nm and Zeta potential of -9.67 ± 0.53 mV. A total of 599 proteins were identified in the OMVs. Proteomics study indicated that the differential expressed proteins induced by OMVs with or without SAAE commonly enriched in P53 and autophagy pathways. Besides, SAAE counteracted the increased production of pro-inflammatory cytokines and attenuated the induction of cell autophagy caused by H. pylori OMVs. Furthermore, SAAE normalized the abnormal regulation of downstream targets (AIFM2 and IGFBP3) in the P53 signaling pathway caused by H. pylori OMVs., Conclusion: SAAE can inhibit the growth and adhesion of H. pylori, reduce the inflammation and autophagy induced by H. pylori OMVs, and combated the abnormal regulation of P53 signaling pathway caused by H. pylori OMVs. These findings may help elucidate the mechanisms through which SAAE reduces the pathogenicity of H. pylori., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Ethnopharmacological Relevance: Phellodendron chinense C.K.Schneid(P. chinense Schneid) is known in TCM as Huang Bo, is traditionally used to support gastrointestinal function and alleviate stomach-related ailments, including gastric ulcer bleeding and symptoms of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) is classified by the WHO as a Group 1 carcinogen. However, the specific activity and mechanism of action of P. chinense Schneid against H. pylori infection remain unclear. It has been noted that Huangjiu processing may alter the bitter and cold properties of P. chinense Schneid, but its effect on antimicrobial activity requires further investigation. Additionally, it remains uncertain whether berberine is the sole antimicrobial active component of P. chinense Schneid., Aim of Study: This study aims to elucidate the anti-H. pylori infection activity of P. chinense Schneid, along with its mechanism of action and key antimicrobial active components., Materials and Methods: Phytochemical analysis was carried out by UPLC-MS/MS. HPLC was employed to quantify the berberine content of the extracts. Antimicrobial activity was assessed using the micro broth dilution method. Morphology was observed using SEM. The impact on urease activity was analyzed through in vitro urease enzyme kinetics. RT-qPCR was employed to detect the expression of virulence genes, including adhesin, flagellum, urease, and cytotoxin-related genes. The adhesion effect was evaluated by immunofluorescence staining and agar culture., Results: P. chinense Schneid exhibited strong antimicrobial activity against both antibiotic-sensitive and resistant H. pylori strains, with MIC ranging from 40 to 160 μg/mL. Combination with amoxicillin, metronidazole, levofloxacin, and clarithromycin did not result in antagonistic effects. P. chinense Schneid induced alterations in bacterial morphology and structure, downregulated the expression of various virulence genes, and inhibited urease enzyme activity. In co-infection systems, P. chinense Schneid significantly attenuated H. pylori adhesion and urease relative content, thereby mitigating cellular damage caused by infection. Huangjiu processing enhanced the anti-H. pylori activity of P. chinense Schneid. Besides berberine, P. chinense Schneid contained seven other components with anti-H. pylori activity, with palmatine exhibiting the strongest activity, followed by jatrorrhizine., Conclusions: This study sheds light on the potential therapeutic mechanisms of P. chinense Schneid against H. pylori infection, demonstrating its capacity to disrupt bacterial structure, inhibit urease activity, suppress virulence gene transcription, inhibit adhesion, and protect host cells. The anti-H. pylori activity of P. chinense Schneid was potentiated by Huangjiu processing, and additional components beyond berberine were identified as possessing strong anti-H. pylori activity. Notably, jatrorrhizine, a core component of P. chinense Schneid, exhibited significant anti-H. pylori activity, marking a groundbreaking discovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Sanguisorba officinalis L. (S. officinalis L.), known as Di Yu (DY) in Traditional Chinese Medicine (TCM), are used to treat burns, vomiting of blood, asthma, intestinal infections, and dermatitis. It has been reported that the root of DY has a significant inhibitory effect on Helicobacter pylori (H. pylori). However, there is currently little research on the composition analysis and anti-H. pylori infection properties of the non-medicinal parts of DY, such as its stems, leaves, and flowers., Aim of Study: The commonly used eradication therapies for H. pylori infection are antibiotic-based therapies. With the increasing antibiotic resistance of H. pylori, it is urgent to find effective alternative therapies. To find alternative therapies and increase the utilization of DY, this study aims to investigate the phytochemistry profile, in vitro anti-H. pylori activity, and preliminary antibacterial mechanism of the non-medicinal parts of DY., Materials and Methods: The non-medicinal parts of DY extracts were obtained by using hot water reflux method. The chemical composition of these extracts was analyzed using colorimetric method, high-performance liquid chromatography (HPLC), and ultra-high-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in vitro anti-H. pylori activity was investigated using broth microdilution method, checkerboard dilution method, time-kill curve, time-inhibition curve, scanning electron microscopy, and transmission electron microscopy. Transcriptional sequencing technology was used to study the effect of DY stems and flowers on the gene expression of H. pylori and explore possible antibacterial mechanisms., Results: The non-medicinal parts of DY contain abundant phytochemicals, such as total phenols and total flavonoids, and possess strong inhibitory and bactericidal activity against both standard and clinical strains of H. pylori in vitro. The MIC was 80-1280 μg/mL and the MBC was 80-2560 μg/mL, and the strength of the antibacterial effects was dependent on the concentration of phytochemicals (total polyphenols, gallic acid and ellagic acid). In addition, the combination of non-medicinal parts of DY with antibiotics, such as amoxicillin, metronidazole, levofloxacin, and clarithromycin, did not result in any antagonistic effects. All of them could disrupt the morphology, internal microscopic and cell wall structures of H. pylori thereby acting as an inhibitor. The mechanism of action was found to be the disruption of H. pylori morphology, internal microstructure, and cell wall. Transcriptomic analysis showed that the non-medicinal parts of DY significantly regulated the gene expression of H. pylori, especially the metabolic pathway., Conclusions: This study analyzed the chemical composition of the non-medicinal parts of DY and confirmed its inhibitory and bactericidal activities against H. pylori, both standard and clinical strains. Additional, the mechanism of inhibition involves disrupting the structure of H. pylori cells, altering gene expression, and interfering with bacterial metabolic pathways. This study provides a reference for further resource utilization and the development of H. pylori drugs using the non-medicinal parts of DY., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Ethnopharmacological Relevance: The dried flower bud of Syzygium aromaticum (L.) Merr. & L.M Perry (S. aromaticum) (Myrtaceae), also known as clove, was used in Traditional Chinese Medicine (TCM) to aid gastrointestinal function and treat stomach disorders including vomiting, flatulence and nausea. And it is a food homology medicine which is a promising candidate for H. pylori treatment. H. pylori is a Gram-negative bacterium that infects approximately 50% of the human population worldwide, which is closely related to multiple gastric diseases, including gastric cancer. However, there are still no sufficient studies on the anti-H. pylori activity of S. aromaticum, especially for the mechanism of action., Aim of Study: This study aimed to study the antibacterial activities of S. aromaticum extracts on both antibiotic-sensitive and -resistant H. pylori strains, and to explore the underlying mechanisms of action., Materials and Methods: The S. aromaticum extracts were obtained by heat reflux extraction and lyophilized to powder form. The phytochemical analyses were performed by High-performance liquid chromatography (HPLC) and UPLC-electrospray ionization mass spectrometry (ESI-MS). In vitro anti-H. pylori activity was evaluated by broth microdilution method. Mechanism of action studies included morphological observation using electron microscopy, determination of expression of virulence genes by reverse transcription quantitative polymerase chain reaction (RT-qPCR), genes expression profile identification by transcriptomic analysis, and exploration of anti-H. pylori infection mechanisms by network pharmacology analysis and western blotting validation., Results: The S. aromaticum extracts, aqueous extract (AE) and 75% hydroalcoholic extract (HE), exerted significant antibacterial activities against both antibiotic-sensitive and -resistant H. pylori strains with MICs of 160∼320 μg/ml, without developing drug resistance. Among them, AE was bactericide to all the tested strains with MBCs of less than 4MIC, while HE was merely bacteriostatic to most of the tested strains with MBCs of 2MIC∼16MIC. Besides, they showed no antagonistic effects in combination with clarithromycin, metronidazole, levofloxacin, and amoxicillin. Additionally, these extracts altered the morphology and ultrastructure and down-regulated the virulence genes expression of H. pylori. And transcriptomic analysis showed that they regulated genes expression of multiple H. pylori biological processes, including tricarboxylic acid cycle (TAC) and pyruvate metabolic pathways. Furthermore, these extracts combated the abnormal activation of PI3K-Akt and MAPK signaling pathways caused by H. pylori infection., Conclusions: Overall, the present study firstly analyzed the chemical compositions of S. aromaticum extracts, and then confirmed their activities on both antibiotic-sensitive and -resistant H. pylori strains. In addition, the mechanisms of action of S. aromaticum extracts against H. pylori were found to be destroying the bacterial structure, down-regulating the expression of virulence genes, and interfering TAC and pyruvate metabolic pathways. Finally, S. aromaticum extracts were found to combated the abnormal activation of PI3K-Akt and MAPK signaling pathways to treat H. pylori infection. This study should accelerate further research and application of S. aromaticum against H. pylori infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Canarium album Raeusch. belongs to the Burseraceae family. Its ripe fruits, known as Qing Guo (QG) in Traditional Chinese Medicine (TCM), are used to treat sore throat, cough, and fish or crab poisoning. QG was reported to have antibacterial activity, and it exerted excellent anti-Helicobacter pylori (H. pylori) activity in our screening of abundant TCM. However, few studies have reported its anti-H. pylori activity and mechanism., Aim of Study: The commonly used eradication therapies for H. pylori infection are antibiotic-based therapies. With the increasing antibiotic resistance of H. pylori, interest in finding alternative therapies has been aroused. This study investigated the phytochemistry profile, in vitro anti-H. pylori activity and possible anti-bacterial mechanism of QG extracts., Materials and Methods: QG extracts were obtained by heat reflux extraction, ultrasonic extraction or liquid-liquid extraction with different solvents. The quantitative and qualitative phytochemical analyses were performed by colorimetric determination, high-performance liquid chromatography (HPLC), and UPLC-electrospray ionization mass spectrometry (ESI-MS). In vitro anti- H. pylori activity was assessed by broth micro-dilution method. Mechanism of action studies included morphological observation using electron microscopy, urease inhibition assay and determination of expression of virulence genes by RT-qPCR., Results: All QG extracts especially ethyl acetate extract (QGEAE) were rich in phenolic components, with the minimum inhibitory concentrations (MICs) on H.pylori of 39-625 μg/ml and minimum bactericidal concentrations (MBCs) of 78-1250 μg/ml. Both aqueous extract (QGAE) and QGEAE could induce the morphological and structural changes of H. pylori, inhibit urease activity with IC 50 of 1093 μg/ml and 332.90 μg/ml, respectively, and down-regulate the virulence genes, such as vacA and cagA., Conclusions: QG may exhibit in vitro anti-H. pylori activity by inhibiting growth, destroying the bacterial structure and down-regulating the expression of virulence factors. Moreover, QG is the homology of food and TCM, which can be considered as a safe and convenient agent against H. pylori infection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

[Display omitted] • Syzygium aromaticum aqueous extract (AE) enhanced innate immunity by inducing macrophages M1 polarization. • AE inhibited the Nrf2/HO-1 signal while activated the TLR4/Myd88 mediated NF-κB and MAPK pathways in macrophages. • AE alleviated Helicobacter pylori infection-related inflammation. Previous studies suggested that Syzygium aromaticum dried buds (S. aromaticum), which is an edible and medicinal herb, possess potential effect on innate immunity and Helicobacter pylori (H. pylori) infection-related inflammation, but the specific action and especially the molecular mechanism have not been well elucidated. The objective of this work was to further explore the effects of Syzygium aromaticum aqueous extract (AE) on innate immunity and H. pylori related-inflammation, especially the potential molecular mechanisms involved. In order to accomplish this, analyses of the phagocytic rate, NO content, ROS level, as well as ELISA, RT-qPCR, and Western blotting et al. assays were carried out. Results indicated that AE increased phagocytic rate, ROS, and cytokine expression levels, meanwhile activated TLR4/MyD88 mediated NF-κB and MAPK pathways and decreased Nrf2/HO-1 signaling. AE also prevented the release of pro-inflammatory substances made by H. pylori -infected RAW 264.7 and GES-1 cells. All things considered, it was shown that AE's ability to boost innate immunity involves inducing macrophage M1 polarization by increasing TLR4/MyD88-mediated NF-κB and MAPK pathways and blocking Nrf2/HO-1 signaling. Additionally, by lowering the production of pro-inflammatory molecules, AE can lessen the inflammation brought on by H. pylori. Considering that S. aromaticum is an edible herbal medicine with immune-enhancing activity and good safety, it deserves further study and utilization for treating diseases including H. pylori infection-related disorders. [ABSTRACT FROM AUTHOR]