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*

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.
Animals ; Cytokines ; Gastric Mucosa ; Indomethacin ; Omeprazole ; pharmacology ; Phytochemicals ; pharmacology ; Random Allocation ; Rats ; Rosaceae ; chemistry ; Stomach Ulcer ; chemically induced ; drug therapy ; Triterpenes ; pharmacology ; Tumor Necrosis Factor-alpha

The stomach is the most common primary site of an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, which is characterized by an indolent clinical course. A diagnosis of gastric MALT lymphoma requires an endoscopic biopsy that should be confirmed by an experienced pathologist. Gastric MALT lymphoma shows a variable endoscopic appearance, including erosion, erythema, discoloration, atrophy, ulcer, and subepithelial lesion. The distribution is often multifocal. Therefore, clinical suspicion and multiple biopsies are essential for an accurate diagnosis. Gastric MALT lymphoma is almost invariably associated with a Helicobacter pylori (H. pylori) infection. H. pylori eradication therapy is the mainstay of treatment, which must be delivered to all patients regardless of the H. pylori infection status or stage. For patients who have failed to achieve remission following eradication therapy, radiotherapy or chemotherapy can be considered. Radiotherapy is an effective treatment modality for a localized stage and shows excellent outcomes. In the presence of disseminated or advanced disease, chemotherapy and/or immunotherapy with the anti-CD20 monoclonal antibody, rituximab, can be applied. Treatment should be individualized according to the stage and symptoms, as well as the patients' preference. Given that the clinical course of gastric MALT lymphoma is usually indolent, watchful waiting may be an adequate strategy in selected cases where scheduled follow-up is guaranteed.
Atrophy ; Biopsy ; Diagnosis ; Drug Therapy ; Erythema ; Follow-Up Studies ; Helicobacter pylori ; Humans ; Immunotherapy ; Lymphoma, B-Cell, Marginal Zone ; Radiotherapy ; Rituximab ; Stomach ; Ulcer ; Watchful Waiting

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

Primary rectal lymphoma is a rare disease among the gastrointestinal (GI) lymphoma. In particular, diffuse large B-cell lymphoma (DLBCL) transformed from mucosa-associated lymphoid tissue (MALT) lymphoma is often the primary type of GI lymphoma, mostly in stomach or duodenum, but has never been reported in rectum. Here we report an unusual case in which a 75-year-old male patient diagnosed with DLBCL transformed from MALT lymphoma in the rectum. The patient was diagnosed as rectal DLBCL transformed from MALT lymphoma as Lugano stage II2 and was treated with chemotherapy (R-CHOP) with CD-20 monoclonal antibody (rituxaimb). Complete remission of multiple lymphadenopathy and mass forming ulcer of the rectum was achieved after 6 cycles of R-CHOP. He has been free from disease for 12 months.
Aged ; B-Lymphocytes* ; Drug Therapy ; Duodenum ; Humans ; Lymphatic Diseases ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell* ; Lymphoma, B-Cell, Marginal Zone* ; Male ; Rare Diseases ; Rectum ; Stomach ; Ulcer

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection. H. pylori eradication can be performed as a primary therapy regardless of H. pylori status. In Korea, six articles were published about low-grade gastric MALT lymphoma with H. pylori. Complete regression rate after H. pylori eradication is reported at 74.5% to 94.4%. Radiotherapy results in favorable clinical long-term outcomes in patients with early-stage gastric MALT lymphoma who fail H. pylori eradication therapy and those who are H. pylori negative. Chemotherapy could be reserved for patients with metastatic or high-grade lymphoma. In gastric MALT lymphoma, patients with polypoid type on initial endoscopy had a higher likelihood of recurrence than those with diffuse infiltration or ulceration types. The depth of invasion, location of lesions, and chromosomal abnormality with t(11;18) together are predictive factors for failure to remission by H. pylori eradication.
Chromosome Aberrations ; Drug Therapy ; Endoscopy ; Helicobacter pylori ; Humans ; Korea ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Lymphoma, Non-Hodgkin ; Radiotherapy ; Recurrence ; Stomach ; Ulcer

Primary squamous cell carcinoma (SCC) of the stomach is a very rare disease. However, the pathogenesis, clinical characteristics, and prognosis of gastric SCC are controversial and remain to be elucidated. Herein, we report a case of primary gastric SCC of the remnant stomach after subtotal gastrectomy. A 65-year-old man was admitted to our hospital due to epigastric discomfort and dizziness. He had undergone subtotal gastrectomy 40 years previously for gastric ulcer perforation. Endoscopy revealed a normal esophagus and a large mass in the remnant stomach. Abdominal computed tomography revealed enhanced wall thickening of the anastomotic site and suspected metachronous gastric cancer. Endoscopic biopsy revealed SCC. Total gastrectomy was performed with Roux-en-Y esophagojejunostomy. A 10-cm tumor was located at the remnant stomach just proximal to the previous area of anastomosis. Pathologic examination showed well-differentiated SCC extended into the subserosa without lymph node involvement (T3N0M0). The patient received adjuvant systemic chemotherapy with 6 cycles of 5-FU and cisplatin regimen, and he is still alive at the 54-month follow-up. According to the treatment principles of gastric cancer, early detection and radical surgical resection can improve the prognosis.
Aged ; Biopsy ; Carcinoma, Squamous Cell* ; Cisplatin ; Dizziness ; Drug Therapy ; Endoscopy ; Epithelial Cells* ; Esophagus ; Fluorouracil ; Follow-Up Studies ; Gastrectomy* ; Gastric Stump* ; Humans ; Lymph Nodes ; Prognosis ; Rare Diseases ; Stomach ; Stomach Neoplasms ; Stomach Ulcer

BACKGROUND/AIMS: Endoscopic hemoclip application is an effective and safe method of endoscopic hemostasis. We conducted a multicenter retrospective study on hemoclip and hemoclip combination therapy based on prospective cohort database in terms of hemostatic efficacy not in clinical trial but in real clinical practice. METHODS: Data on endoscopic hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively collected from February 2011 to December 2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were enrolled in this study. Subjects were divided into three groups: Group 1 (n=62), hemoclipping only; group 2 (n=88), hemoclipping plus epinephrine injection; and group 3 (n=36), hemocliping and epinephrine injection plus other endoscopic hemostatic modalities. Primary outcomes included rebleeding, other therapeutic management, hospitalization period, fasting period and mortality. Secondary outcomes were bleeding associated mortality and overall mortality. RESULTS: Active bleeding and peptic ulcer bleeding were more common in group 3 than in group 1 and in group 2 (p<0.001). However, primary outcomes (rebleeding, other management, morbidity, hospitalization period, fasting period and mortality) and secondary outcomes (bleeding associated mortality and total mortality) were not different among groups. CONCLUSIONS: Combination therapy of epinephrine injection and other modalities with hemoclips did not show advantage over hemoclipping alone in this prospective cohort study. However, there is a tendency to perform combination therapy in active bleeding which resulted in equivalent hemostatic success rate, and this reflects the role of combination therapy in clinical practice.
Adult ; Aged ; Angiography ; Cohort Studies ; Combined Modality Therapy ; Databases, Factual ; Epinephrine/therapeutic use ; Female ; Gastrointestinal Hemorrhage/etiology/*therapy ; *Hemostasis, Endoscopic ; Humans ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/therapeutic use ; Retrospective Studies ; Stomach Ulcer/complications/drug therapy/pathology ; Surgical Instruments ; Treatment Outcome

Helicobacter pylori can cause variety of upper gastrointestinal disorders such as peptic ulcer, mucosa associated lymphoid tissue (MALT)-lymphoma, and gastric cancer. The prevalence of H. pylori infection has significantly decreased in Korea since 1998 owing to active eradication of H. pylori. Along with its decrease, the prevalence of peptic ulcer has also decreased. However, the mean age of gastric ulcer increased and this is considered to be due to increase in NSAID prescription. Gastric cancer is one of the leading causes of cancer deaths in Korea and Japan, and IARC/WHO has classified H. pylori as class one carcinogen of gastric cancer. Despite the decreasing prevalence of H. pylori infection, the total number of gastric cancer in Korea has continuously increased from 2006 to 2011. Nevertheless, the 5 year survival rate of gastric cancer patients significantly increased from 42.8% in 1993 to 67% in 2010. This increase in survival rate seems to be mainly due to early detection of gastric cancer and endoscopic mucosal dissection treatment. Based on these findings, the prevalence of peptic ulcer is expected to decrease even more with H. pylori eradication therapy and NSAID will become the main cause of peptic ulcer. Although the prevalence of gastric cancer has not changed along with decreased the prevalence of H. pylori, gastric cancer is expected to decrease in the long run with the help of eradication therapy and endoscopic treatment of precancerous lesions.
Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Gastrointestinal Diseases/complications/*epidemiology ; Helicobacter Infections/complications/drug therapy/epidemiology ; Humans ; Lymphoma, B-Cell, Marginal Zone/epidemiology ; Peptic Ulcer/epidemiology/etiology ; Prevalence ; Stomach Neoplasms/etiology/mortality/pathology