The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1β, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.
Animals ; Mice ; Stomach Ulcer/drug therapy* ; Proto-Oncogene Proteins c-akt ; Animal Experimentation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Vascular Endothelial Growth Factor A ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE₂), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE₂ and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE₂ biosynthesis.
Rats ; Animals ; Stomach Ulcer/pathology* ; Antioxidants/therapeutic use* ; Ranitidine/adverse effects* ; Aesculus ; Ulcer/drug therapy* ; Quercetin ; Plant Extracts/chemistry* ; Indomethacin/therapeutic use* ; Glutathione ; Superoxide Dismutase ; Rutin/adverse effects* ; Prostaglandins/adverse effects* ; Phytochemicals/therapeutic use*

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.
Animal Experimentation ; Animals ; Capsules ; Gastric Mucosa/metabolism* ; Humans ; Network Pharmacology ; Rats ; Stomach Ulcer/genetics*

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.
Animals ; Fibrinolytic Agents ; Humans ; Integrins ; Leukocytes ; Macrophage-1 Antigen ; Rats ; Stomach Ulcer ; Tablets ; Thrombosis

OBJECTIVE: To observe the effect of acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) on intestinal flora and Toll-like receptors-4 (TLR4) in brain and intestinal tissue in rats with stress gastric ulcer (SGU), and to explore the possible mechanism of acupuncture for SGU. METHODS: Thirty-one male SD rats were randomly divided into a blank group ( RESULTS: Compared with the blank group, the gastric mucosal damage index was significantly increased in the model group ( CONCLUSION Acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) could alleviate SGU in rats, and its mechanism may be related to increasing the diversity of intestinal flora, promoting the disorder of intestinal flora to normal, and reducing the overexpression of TLR4 in brain and intestinal tissues.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Brain ; Gastrointestinal Microbiome ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer/therapy* ; Toll-Like Receptor 4/genetics*

To investigate the protective effect of (FD) against ethanol-induced gastric ulcer and its mechanism. : Human gastric epithelial GES-1 cells were divided into normal control group, model control group, FD 95% alcohol extract group, FD 50% alcohol extract group and FD decoction extract group. Gastric ulcer was induced by treatment with 1% ethanol in GES-1 cells. The cell proliferation was detected with MTT method in each group. Sixty SD rats were randomly divided into normal control group, model control group, ranitidine group and low-dose, medium-dose, high-dose FD 95% alcohol extract groups (150, 300, 600 mg/kg). The corresponding drugs were administrated by gavage for The gastric ulcer model was induced by intragastric administration of anhydrous ethanol. The gastric ulcer area and ulcer inhibition rate of rats were measured in each group; the degree of gastricmucosal damage was observed by scanning electron microscopy; the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) in gastric tissues were detected by ELISA method. : 95% alcohol extract of FD had the strongest protective effect on proliferation of GES-1 cells. In animal experiments, compared with the normal control group, a large area of ulcers appeared on the gastric mucosa in the model control group, while the ulcer areas of the FD groups and ranitidine group were significantly smaller than that of the model control group (all <0.05). Compared with the model control group, FD groups and ranitidine group significantly reduced the levels of TNF-α, IL-1β, IL-6 in serum and the MDA content in the gastric tissues, and increased the activity of SOD, CAT and GSH in gastric tissues (all <0.05). : The 95% alcohol extract of FD can reduce the levels of TNF-α, IL-1β and IL-6 in serum and the content of MDA in gastric tissues, and increase the activity of SOD, CAT and GSH in gastric tissues to achieve the protective effect against gastric ulcer.
Animals ; Ethanol/toxicity* ; Gastric Mucosa ; Malondialdehyde ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer/prevention & control* ; Superoxide Dismutase

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery. METHODS: Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora. RESULTS: Compared with the control group, the GMDI of rats in the model group was increased (<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (<0.05), the diversity index Simpson was increased (<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (<0.01, <0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (<0.05) and the diversity index Simpson decreased (<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (<0.01), the recovery of gastric mucosal injury was better than that of the medication group. CONCLUSION Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Microbiome ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; microbiology ; therapy

OBJECTIVES: To compare the features of patients with peptic ulcer between Han and Uyghur ethnicity from 2013 to 2018 in Xinjiang and to provide the evidence of prevention and treatment for the different ethnicity. METHODS: Data of 3 586 patients with peptic ulcer (3 293 Han and 293 Uyghur) in the Karamay Central Hospital of Xinjiang, including the detection rate of peptic ulcer, () detection rate of population, season, gender, lesion location and complication, were collected from January 2013 to December 2018 and compared between 2 nationalities. RESULTS: There were significant difference in the detection rate of peptic ulcer and population's between Han and Uyghur (<0.01). The detection rates for peptic ulcer of Han were sustainable declined from 15.20% to 10.23%, while Uyghur's detective rates for peptic ulcer were raised again from 17.49% to 8.38%. The detection rate of Uyghur's population was higher than that of Han (<0.01). There were significant difference in the season's detection rate for peptic ulcer between Han and Uyghur (<0.01). The detection rate for peptic ulcer of Han was the highest in the winter, while that of Uyghur was the highest in the spring. The detective rate of Uyghur's peptic ulcer was significant higher than that of Han in the spring (<0.01). The detection rates for peptic ulcer of 2 nationality were the highest at ≤25 age groups, the detection rate for Uyghur's peptic ulcer was higher than that of Han at ≤35 age groups (<0.05). There were more men than women in peptic ulcer in the 2 nationalities. The approximate proportion was 2꞉1. The rates of multiple gastric ulcer and compound duodenal ulcer of Han were more than those of Uyghur (<0.05), but the rate for pyloric obstruction of Uyghur patient was higher than that of Han (<0.05). CONCLUSIONS There are statistical difference in detection rate of PU, detection rate of population, morbidity season, age, complication and the rate of complex ulcer between Han and Uyghur, However, there aren't statistical difference in detection rate of peptic ulcer patient, the gender, lesion location between the 2 nationalities during last 6 years.
Child, Preschool ; Duodenal Ulcer ; Ethnic Groups ; Female ; Helicobacter Infections ; Helicobacter pylori ; Humans ; Male ; Stomach Ulcer

OBJECTIVES: To detemine preventive effects of compound formula Rhizoma Coptidis and Atractylodes on mice with gastric-ulcer. METHODS: The mice were randomly divided into a normal group, a gastric ulcer group, a ranitidine positive drug group, a Rhizoma Coptidis group, an Atractylodes group, and a Rhizoma Coptidis plus Atractylodes group (the ratios of Coptidis to Atractylodes were 9꞉1, 8꞉2, 7꞉3, 6꞉4, 5꞉5, or 4꞉6, respectively). Gastric ulcer models were established by intragastric administration of anhydrous ethanol after 6 days of preventive infusion. The mice were killed 6 days after the treatments. The whole stomach was opened to observe gross morphology of gastric mucosa. The pathological changes of gastric tissue were observed under microscope, and serum samples were collected to detect the contents of superoxide dimutase (SOD), malondialdehyde (MDA), NO, and endothelin-1 (ET-1). RESULTS: The Rhizoma Coptidis and Atractylodes decoction significantly decreased ulcer area (<0.001), and the effects of compound formula are better than those of Coptidis and Atractylodes alone (<0.05, <0.01, or <0.001). The anti-ulcer effect of compound formula (Coptidis꞉Atractylodes=6꞉4) was the best one, and the anti-gastric ulcer effect of the high-dose group was significantly better than that of the ranitidine-positive group (<0.001). The ranitidine positive drug group, the high-dose group of Rhizoma Coptidis, the high-dose group of Atractylodes, and the high-dose group of Rhizoma Coptidis-Atractylodes (6꞉4) significantly reduced MDA, ET-1 (<0.01 or <0.001), and significantly increased SOD, NO in serum (<0.01 or <0.001). CONCLUSIONS Rhizoma Coptidis and Atractylodes decoction exerts the effect on preventing ethanol-induced gastric ulcer in mice in a ratio-dependent and dose-dependent manner. The mechanism might be related to anti-oxidation and relaxion of blood vessels. The combination of the two drugs shows a synergistic effect.
Animals ; Atractylodes ; Drugs, Chinese Herbal ; Gastric Mucosa ; Mice ; Stomach Ulcer

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis, which is characterized by fever, lymphadenopathy, and sore throat. On the other hand, gastrointestinal symptoms of EBV infection like dyspepsia, abdominal pain are non-specific and rarely encountered, which means it is difficult to diagnose gastric involvement of EBV infection without suspicion. The relation between gastric carcinoma and gastric lymphoma associated with EBV infection is well defined, but relations with other EBV-associated gastrointestinal diseases such as gastritis and peptic ulcer disease have rarely been reported. We report a case of benign gastric ulcer with EBV infection confirmed by endoscopic and histological findings.
Abdominal Pain ; Dyspepsia ; Epstein-Barr Virus Infections ; Fever ; Gastritis ; Gastrointestinal Diseases ; Hand ; Helicobacter pylori ; Herpesvirus 4, Human ; In Situ Hybridization ; Infectious Mononucleosis ; Lymphatic Diseases ; Lymphoma ; Peptic Ulcer ; Pharyngitis ; Stomach Ulcer