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BackgroundTriphala, is a composite of three individual botanical drugs: Terminalia chebula, Terminalia bellirica, and Emblica officinalis. It exhibits properties such as heatclearing, anti-inflammatory, anti-fatigue, antioxidant, and antibacterial effects,making it extensively utilized in India and Tibet. It has been found to exhibitinhibitory effects on Helicobacter pylori (H. pylori); however, further comprehensive research is still needed to elucidate its specific antibacterial mechanism. The present study investigates the in vitro antibacterial activity and antibacterial mechanism of Triphala against H. pylori.MethodsOurs research investigates the in vitro inhibitory activity of Triphala on multiple standard and clinical strains using microdilution broth method, time-kill curve, time-bactericidal curve and scanning electron microscopy (SEM). Furthermore, the antibacterial mechanism of Triphala is further explored through experiments on urease activity, biofilm formation, anti-adhesion properties, virulence actor assays using RT-qPCR and Western Blotting techniques.ResultsThe research findings indicate that Triphala exhibits a minimum inhibitory concentration of 80–320 μg/mL against both standard and clinical strains of H. pylori. Triphala exerts its anti-H. pylori effect by perturbing the microstructure of H. pylori, downregulating adhesion-associated genes (alpA, alpB, babA), urease-related genes (ureA, ureB, ureE, ureF), and flagellar genes (flaA, flaB); inhibiting bacterial adhesion, biofilm formation, urease activity as well as CagA protein expression.DiscussionThese findings suggest that Triphala exerts inhibitory effects on H. pylori activity through multiple mechanisms, underscoring its potential as a new drug for the prevention and treatment of H. pylori infection.

Gastric cancer is a significant health concern worldwide. Helicobacter pylori (HP) infection is associated with gastric cancer risk, but differences between HP-infected and HP-free gastric cancer have not been studied sufficiently. The objective of this study was to investigate the effects of HP infection on the viability and migration of gastric cancer cells and identify potential underlying genetic mechanisms as well as their clinical relevance. Cell counting kit-8, lactate dehydrogenase, wound healing, and transwell assay were applied in the infection model of multiple clones of HP and multiple gastric cancer cell lines. Genes related to HP infection were identified using bioinformatics analysis and subsequently validated using real-time quantitative PCR. The association of these genes with immunity and drug sensitivity of gastric cancer was analyzed. Results showed that HP has no significant impact on viability but increases the migration of gastric cancer cells. We identified 1405 HP-upregulated genes, with their enriched terms relating to cell migration, drug, and immunity. Among these genes, the 82 genes associated with survival showed a significant impact on gastric cancer in consensus clustering and LASSO prognostic model. The top 10 hub HP-associated genes were further identified, and 7 of them were validated in HP-infected cells using real-time quantitative PCR, including ERBB4, DNER, BRINP2, KCTD16, MAPK4, THPO, and VSTM2L. The overexpression experiment showed that KCTD16 medicated the effect of HP on gastric cancer migration. Our findings suggest that HP infection may enhance the migratory potential of gastric cancer cells and these genes might be associated with immunity and drug sensitivity of gastric cancer. In human subjects with gastric cancer, HP presence in tumors may affect migration, immunity, and drug sensitivity.

BackgroundHelicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism.MethodsChemical components of HZQYF were studied using UHPLC–MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF’s antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein.ResultsMinimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80–160 μg/mL, and minimum bactericidal concentration (MBC) values were 160–320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity.ConclusionPresent studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations.

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.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as “Haritaki”. The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography–MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Sanguisorba officinalis L., a traditional Chinese medicine (TCM) called DiYu (DY) in China, has a strong tradition of utilization as a scorching, blood-cooling, and hemostatic medication, and was used for cancer prevention and treatment due to its potential immune-enhancing and hematological toxicity-reducing effects. Previous studies have reported significant effects of DY on cancers including colorectal cancer (CRC), which is one of the most common malignancies worldwide. The first-line cure 5-fluorouracil (5-FU) plays decisive commerce in the sedative of CRC as a clinically available chemotherapeutic agent. One of the primary causes of cancer treatment failure is the acquisition of chemotherapy drug resistance. In order to successfully combat the emergence of chemoresistance, it is essential to identify herbs or traditional Chinese medicine that have adjuvant therapeutic effects on CRC. Therefore, this study aimed to determine whether DY could improve the sensitivity, conquer the chemoresistance of 5-FU-resistant CRC cells, and investigate its intrinsic mechanism. Materials and methods: MTT, Hoechst 33258 staining, and flow cytometry assays were used to determine the anticancer activity of DY alone or in combination with 5-FU against 5-FU-resistant CRC cells (RKO-R and HCT15-R) and wound healing assays were conducted to detect cell migration. Transcriptomic techniques were carried out to explore the effect and mechanism of DY on drug-resistant CRC cells. Western Blot and RT q-PCR assays were performed to validate the mechanism by which DY overcomes drug-resistant CRC cells. Results: These results indicated that DY alone or in combination with 5-FU significantly inhibited the proliferation and the migration of resistant CRC cells, and potentiated the susceptibility of 5-FU to drug-resistant CRC cells. GO and KEGG enrichment analysis showed that the mechanisms of drug resistance in CRC cells and DY against drug-resistant CRC cells highly overlapped, involved in the modulation of biological processes such as cell migration, positive regulation of protein binding and cytoskeleton, and MAPK (Ras-ERK-MEK), PI3K/Akt, and other signaling pathways. Moreover, DY can mediate the expression of p-R-Ras, p-ERK1/2, p-MEK1/2, p-PI3K, p-AKT, HIF-1A and VEGFA proteins. In addition, DY significantly suppressed the expression of AKT3, NEDD9, BMI-1, and CXCL1 genes in resistant CRC cells. Conclusion: In conclusion, DY could inhibit the proliferation and migration of 5-FU-resistant cells and strengthen the sensitivity of 5-FU to CRC-resistant cells. Furthermore, DY may prevail over chemoresistance through the Ras/MEK/ERK and PI3K/Akt pathways. These findings imply that DY may be a potential drug for clinical treatment or adjuvant treatment of drug-resistant CRC.

Abstract Background Recently, defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction. Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects, which causes glyphosate an environmental contaminant found in soil, water and food. During the last few years, the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity. In this study, using porcine models, we investigated effects of glyphosate on organelle functions during oocyte meiosis. Results The results showed glyphosate exposure disrupted porcine oocyte maturation. Expression levels of cumulus expansion-related genes were interfered, further indicating the meiotic defects. The damaging effects were mediated by destruction of mitochondrial distribution and functions, which induced ROS accumulation and oxidative stress, also indicated by the decreased mRNA expression of related antioxidant enzyme genes. We also found an interference of endoplasmic reticulum (ER) distribution, disturbance of Ca2+ homeostasis, as well as fluctuation of ER stress, showing with the reduced ER stress-related mRNA or protein expression, which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes. Moreover, glyphosate exposure induced the disruption of lysosome function for autophagy, showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression. Additionally, our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure, which might affect protein synthesis and transport. Conclusions Collectively, our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions.

BackgroundColorectal cancer (CRC) is the most common malignant cancer worldwide. Sanguisorba officinalis has been shown to have anti-inflammatory, anti-bacterial, antioxidant, and anti-tumor effects, while its molecular mechanism against CRC remains unclear. The aim of this study is to explore the underlying mechanism of S. officinalis against CRC cell lines using network pharmacology and transcriptomic sequencing methods.MethodFirstly, the active ingredients and potential targets of S. officinalis against CRC were screened from databases. Secondly, the networks of ingredient–target, ingredient–target–CRC and protein–protein interaction were constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of network pharmacology and transcriptomic sequencing were performed. Finally, the effect of S. officinalis against CRC was verified by in vitro experiments.ResultsIn total, 14 active ingredients and 273 potential targets against CRC were identified in S. officinalis by network pharmacology. PI3K–Akt, HIF-1, and MAPK signaling pathways related to cell proliferation were regulated by S. officinalis in enrichment analyses and transcriptomic sequencing. In vitro, S. officinalis inhibited the proliferation and migration of CRC cells and arrested the cell cycle at the G0–G1 phase. The western blot showed that S. officinalis downregulated the expression of p-PI3K, p-Akt, HIF-1A, VEGFA, cyclin D1, c-Myc, and p-MAPK proteins in CRC cells.ConclusionIn conclusion, network pharmacology and transcriptomic sequencing analyses, in combination with in vitro studies, have been successfully applied to study the underlying mechanism of S. officinalis against CRC cells. Our results demonstrate that S. officinalis suppresses the proliferation, survival, and migration of CRC cells through regulating the PI3K–Akt, HIF-1, and MAPK signaling pathways.