ABSTRACT
BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.
Subject(s)
Plant Preparations , Stomach Ulcer , Rats , Male , Animals , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Antioxidants/pharmacology , Antioxidants/therapeutic use , NLR Family, Pyrin Domain-Containing 3 Protein , Ethanol/adverse effects , Ulcer/drug therapy , Gastrins/therapeutic use , Pyroptosis , Rats, Wistar , Plant Extracts/pharmacology , Signal TransductionABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Baizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored. AIM OF THE STUDY: This study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD). METHODS: To simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin ß (ß-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated. RESULTS: The results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (ß-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.
Subject(s)
Atractylodes , Rhizome , Humans , Female , Pregnancy , Mice , Animals , Ghrelin/therapeutic use , Pregnancy Outcome , Cholesterol, LDL , Fetal Weight , Diarrhea/drug therapy , Gastrins , Water , RNA, MessengerABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear. AIM OF THE STUDY: To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms. MATERIALS AND METHODS: Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1ß, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD. RESULTS: The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1ß, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5. CONCLUSION: Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD.
Subject(s)
Dyspepsia , Male , Mice , Animals , Dyspepsia/drug therapy , Ghrelin/therapeutic use , Tumor Necrosis Factor-alpha , Gastrins , Interleukin-6 , Interleukin-1beta , Deoxycholic AcidABSTRACT
OBJECTIVE: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG). METHODS: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]. RESULTS: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways. CONCLUSIONS: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.
Subject(s)
Bile Reflux , Drugs, Chinese Herbal , Gastritis , Animals , Rats , Gastrins , Chromatography, High Pressure Liquid , Molecular Docking Simulation , Network Pharmacology , Powders , Gastritis/drug therapy , Tumor Necrosis Factor-alpha , PhosphatidylinositolsABSTRACT
OBJECTIVE: To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP). METHODS: We established an animal model of SDS in Sprague-Dawley () rats by treating them with deficiency-inducing factors, including irregular feeding and tail clamping. Mice were administered Fuling () and its extracts (raw/cooked powder, aqueous/alcohol extract) by gavage once a day for 21 d. The body weight, rectal temperature, and spleen and thymus organ coefficients were calculated. The levels of motilin (MTL), gastrin (GAS), aquaporin 2 (AQP2), interleukin 2 (IL-2), IL-4, and 5-hydroxytryptamine (5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay. RESULTS: Fuling () and its extracts did not change the body weight, rectal temperature, and organ coefficients of the spleen and thymus. However, it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2. In addition, the levels of IL-4 and 5-HT showed no significant alteration. CONCLUSIONS: These results suggested the crucial function of () in SDSP, especially promoting digestive function and water metabolism.
Subject(s)
Spleen , Wolfiporia , Rats , Mice , Animals , Rats, Sprague-Dawley , Interleukin-2/genetics , Interleukin-4 , Serotonin , Aquaporin 2 , Body Weight , Gastrins/pharmacologyABSTRACT
Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 µg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.
Subject(s)
Gastrinoma , Multiple Endocrine Neoplasia Type 1 , Zollinger-Ellison Syndrome , Humans , Zollinger-Ellison Syndrome/diagnosis , Zollinger-Ellison Syndrome/complications , Zollinger-Ellison Syndrome/surgery , Gastrinoma/diagnosis , Gastrinoma/pathology , Gastrinoma/surgery , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/diagnosis , Multiple Endocrine Neoplasia Type 1/pathology , Secretin , Gastrins , Proton Pump InhibitorsABSTRACT
OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.
Subject(s)
Acupuncture Therapy , Diabetes Mellitus , Gastroparesis , Humans , Gastroparesis/etiology , Gastroparesis/therapy , Spleen , Domperidone/therapeutic use , Gastrins , Motilin , Reactive Oxygen Species , Tumor Necrosis Factor-alpha , Interleukin-6 , Blood Glucose , Glycated Hemoglobin , Liver , Superoxide Dismutase , Acupuncture Points , Diabetes Mellitus/therapyABSTRACT
INTRODUCTION: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients. METHODS: Eighty patients with colorectal cancer were randomized within 2 weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA. RESULTS: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the TCM syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased. CONCLUSION: The curative effect and safety of modified BSS were statistically significant.
Subject(s)
Colorectal Neoplasms , Gastrointestinal Diseases , Humans , Gastrins , Loperamide , Motilin , Single-Blind Method , DiarrheaABSTRACT
The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Peptic Ulcer , Probiotics , Humans , Helicobacter Infections/drug therapy , Bismuth/pharmacology , Bismuth/therapeutic use , Metronidazole/pharmacology , Metronidazole/therapeutic use , Proton Pump Inhibitors/pharmacology , Gastrins/pharmacology , Gastrins/therapeutic use , Motilin/pharmacology , Motilin/therapeutic use , Tablets, Enteric-Coated/pharmacology , Tablets, Enteric-Coated/therapeutic use , Drug Therapy, Combination , Peptic Ulcer/drug therapy , Peptic Ulcer/microbiology , Amoxicillin/therapeutic use , Amoxicillin/pharmacology , Anti-Bacterial Agents/therapeutic use , Probiotics/therapeutic use , Pectins/pharmacology , Pectins/therapeutic use , Somatostatin/pharmacology , Somatostatin/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: gastric cancer is the fifth most prevalent cancer and the fourth cause of death because of cancer. In Iran, northern and northwestern regions are considered gastric cancer hot spots. Identifying serum biomarkers could be helpful in early diagnosis of patients with gastric adenocarcinoma (GAC). Increase in progastrin level has been reported in different cancers. Given the diagnostic value of this biomarker, this study aimed to determine the diagnostic role of progastrin serum biomarker in patients with gastric cancer. METHODOLOGY: In this case-control study, forty patients with gastric cancer who were diagnosed by endoscopy and pathologic findings and visited Mazandaran Comprehensive Cancer Center. The participants had received no treatment yet and entered this study. The participants in case group were compared with the control group including forty-two individuals with no history of gastrointestinal cancer in their first-degree relatives and visiting the lab for routine tests. Progastrin serum level was assessed using ELISA kit. The Kruskal-Wallis test and Mann Whitney test, both non-parametric) were used for statistical analysis and the relation between the variables was examined using Pearson's correlation coefficient at 95% confidence level in SPSS 16. FINDINGS: In this study, progastrin serum level was significantly higher in patients with gastric cancer compared with normal participants (P = 0.035). Progastrin serum level had no significant relation with tumor clinicopathologic parameters (p-value > 0.05). CONCLUSION: Increase in progastrin may be utilized as a predictive factor for gastric cancer.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Case-Control Studies , Biomarkers, Tumor , GastrinsABSTRACT
it was aimed to investigate the efficacy and safety of cupping moxibustion in patients with functional diarrhea. 51 patients diagnosed with functional diarrhea from January 2021 to December 2021 were selected as the objects, and they were randomly divided into the control group (oral montmorillonite powder) and the experiment group (oral montmorillonite powder combined with cupping moxibustion). The number of diarrheas, Bristol stool, traditional Chinese medicine (TCM) syndromes, clinical efficacy indexes, self-rating anxiety scale (SAS) score, the MOS item short from health survey (SF-36) scale score, peripheral blood cell levels of CD4+, CD8+, and Th17, gastrin (GAS), motilin (MTL), and cholecystokinin (CCK) levels was assessed before and after treatment. The adverse events were also recorded. Compared with those before treatment, all indexes of both groups were significantly improved (P<0.05). Compared with those of the control group, the number of diarrheas, Bristol stool, TCM syndrome score, SAS score, and CD8+ cell levels was significantly decreased after treatment in the experiment group (P<0.05). The clinical cure rate (48.0% vs. 73.1%), SF-36 score, GAS, MTL, CCK contents, and CD4+, and Th17 cell levels were significantly increased (P<0.05). No significant difference was in the incidence of adverse events between the two groups (P>0.05). It could be suggested that cupping moxibustion could be applied in the treatment of functional diarrhea, improving the clinical symptoms, relieving anxiety, enhancing gastrointestinal and immune functions, and promoting the quality of life of patients significantly.
Subject(s)
Moxibustion , Bentonite , Cholecystokinin , Diarrhea/therapy , Gastrins , Humans , Immunity , Motilin , Powders , Quality of LifeABSTRACT
Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical constitutes, gastroprotective effects, and the active fraction of C. fimbriata, as well as elucidating the underlying mechanisms. Firstly, four in vitro antioxidant tests were applied to determine the oxidation resistance of C. fimbriata methanol extract and its fractions. The gastroprotective effects were evaluated in ethanol-induced gastric ulcer rats, gastric histopathology was visualized by H&E staining, and the acidity of gastric juice was measured by titrating with NaOH solution. The contents of malondialdehyde, catalase, superoxide dismutase, gastrin, and the activity of H+K+-ATPase were estimated using commercial kits. EtOAc fraction of C. fimbriata methanol extract (CfEF) exhibited significant gastroprotective effects by ameliorating stomach pathological changes and elevating the pH value of gastric juice. It also manifested remarkable antioxidant activities in vitro and in vivo. Using various chromatographic methods and spectroscopic techniques, 22 compounds were isolated and characterized from CfEF, in which alkaloids were the predominant components. All of these substances were derived from C. fimbriata for the first time. The results indicated that CfEF is a promising source of gastroprotective agents. The antioxidant activity of this herb, as well as prevention of gastrin secretion and inhibition of H+K+ -ATPase, was found to be the underlying mechanism of action.
Subject(s)
Anti-Ulcer Agents , Orchidaceae , Stomach Ulcer , Animals , Anti-Ulcer Agents/therapeutic use , Antioxidants/therapeutic use , Gastric Mucosa , Gastrins/metabolism , H(+)-K(+)-Exchanging ATPase/metabolism , Methanol/chemistry , Plant Extracts/therapeutic use , Rats , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & controlABSTRACT
We aim to investigate the therapeutic effect of self-made Hewei decoction based on the differences-in-differences (DID) model for treating chronic atrophic gastritis and its effect on the gastrin and pepsinogen expression. A total of 166 chronic atrophic gastritis patients treated in our hospital from January 2019 to September 2020 were recruited and randomly assigned to a treatment group and a control group (n = 83 per group). In the control group, patients were given conventional western medicine. In the treatment group, patients were administered self-made Hewei decoction besides conventional western medicine. The general data, total effective rate, and histological changes before and after treatment were compared between the two groups. The DID model was utilized to compare the changes in three items of gastric function and traditional Chinese medicine (TCM) syndrome scores at various time points (before treatment and 1, 3, 6, and 12 months after treatment) between the two groups. In the treatment group, 5 cases were lost to follow-up, and 78 cases remained. In the control group, 4 cases were lost to follow-up, and 79 cases remained. The total effective rate in the treatment group (93.59%) was significantly higher than that in the control group (82.28%) (P < 0.05). The histological score was not significantly different between the two groups before treatment (P > 0.05). The histological score at 12 months after treatment was lower than those before treatment in the two groups (P < 0.05). The histological score was lower in the treatment group than that in the control group (P < 0.05). After treatment, the TCM syndrome score and PGR17 level were lower in the treatment group than those in the control group at each time point (P < 0.05). PGI and PGII levels were higher in the treatment group than those in the control group at each time point (P < 0.05). DID regression model showed that TCM syndrome score and PGR17 level decreased by 106.2% and 65.8%, respectively, after treatment in patients with chronic atrophic gastritis (P < 0.05), but the treatment mode was opposite to the overall therapeutic effect in terms of time. The PGI and PGII levels increased by 102.9% and 97.8%, respectively, in patients with chronic atrophic gastritis (P < 0.05), and the treatment mode was the same as the overall therapeutic effect in terms of time. There was no significant difference in the therapeutic effect between the two groups at 1 month after treatment. A significant difference in the therapeutic effect was detected between the two groups at 3 months after treatment, and the difference showed a decreasing trend after 6 months after treatment. Self-made Hewei decoction can improve the histological alterations in chronic atrophic gastritis, relieve clinical symptoms, and ameliorate the expression levels of three items of gastric function.
Subject(s)
Gastritis, Atrophic , Helicobacter pylori , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Gastrins , Gastritis, Atrophic/diagnosis , Gastritis, Atrophic/drug therapy , Gastritis, Atrophic/pathology , Humans , Pepsinogen A/metabolismABSTRACT
Peptic ulcer is an acid-induced lesion that is usually found in the stomach and duodenum. It is usually a case of imbalance between the acid (and other injurious factors) and the mucosal defense mechanisms. Indomethacin is one of the most ulcerogenic drugs that is prescribed over-the-counter for the management of musculoskeletal problems. Capparis spinosa is one of the most important species in the Capparidaceae family, which has a wide range of diversity. Caper (Capparis spinosa L.) is a common member of the genus Capparis (Capparidaceae family). The present study was designed to compare the effect of C. spinosa extract as a gastroprotective agent with indomethacin as an induction agent and ranitidine as a standard drug. To this aim, 40 adult male Wistar rats were randomly divided into 4 groups (n=10 each), including Control +: indomethacin-treated group, Control -: receiving physiological saline solution, C.S: C. spinosa-treated group; and ranitidine-treated group (50 mg/kg) as a standard agent for the treatment of the gastric ulcer. After the experimental period, all the animals were sacrificed by anesthesia overdose and their stomachs were removed. The gastroprotective effect of C. spinosa was investigated by studying prostaglandin E2 (PGE2), Gastrin, anti-tumor necrosis factor alpha (TNF-α), and Interleukin 1 beta (IL1-ß), along with histopathological examination. The results showed a significant increase in PGE2 levels in the ranitidine-treated group with a significant reduction in Gastrin, TNF-α, and IL1-ß. The recorded data obtained from the histopathological study showed a significant improvement in the treated group with the extract of C. spinosa. The study concluded that C. spinosa had gastroprotective properties possibly through enhancing PGE2 which was acting as anti-inflammatory inhibiting neutrophil infiltration.
Subject(s)
Capparis , Plant Extracts , Stomach Ulcer , Animals , Male , Rats , Dinoprostone , Gastrins , Indomethacin/toxicity , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Ranitidine/pharmacology , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & control , Tumor Necrosis Factor-alphaABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.
Subject(s)
Citrus/chemistry , Plant Oils/pharmacology , Pogostemon/chemistry , Stomach Ulcer/drug therapy , Animals , Dinoprostone/blood , Dinoprostone/genetics , Dinoprostone/metabolism , Gastrins/blood , Gastrins/genetics , Gastrins/metabolism , Gene Expression Regulation/drug effects , Male , Pepsinogen C/blood , Pepsinogen C/genetics , Pepsinogen C/metabolism , Plant Oils/chemistry , Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Restraint, Physical/adverse effects , Serotonin/blood , Serotonin/genetics , Serotonin/metabolism , Stomach Ulcer/etiologyABSTRACT
To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractionsâfor 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.
Subject(s)
Colon/drug effects , Defecation/drug effects , Diarrhea/prevention & control , Gastrointestinal Agents/pharmacology , Intestine, Small/drug effects , Rheum , Wolfiporia , Amylases/blood , Animals , Colon/metabolism , Colon/pathology , Colon/physiopathology , Diarrhea/chemically induced , Diarrhea/metabolism , Diarrhea/physiopathology , Disease Models, Animal , Female , Gastrins/blood , Gastrointestinal Agents/isolation & purification , Intestine, Small/metabolism , Intestine, Small/physiopathology , Male , Mice , Vasoactive Intestinal Peptide/metabolism , Wolfiporia/chemistry , Xylose/bloodABSTRACT
Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.
Subject(s)
Colon/metabolism , Colostrum/microbiology , Constipation/chemically induced , Constipation/drug therapy , Constipation/microbiology , Pediococcus pentosaceus/metabolism , Acetylcholinesterase , Animals , Bacteria , Fatty Acids, Volatile/metabolism , Feces , Gastrins , Gastrointestinal Transit/drug effects , Gastrointestinal Transit/physiology , Hormones/blood , Humans , Intestines , Loperamide/adverse effects , Male , Mice , Mice, Inbred BALB C , Milk, Human/microbiology , Motilin , Neurotransmitter Agents/blood , Oxidative Stress , Pediococcus pentosaceus/genetics , Pediococcus pentosaceus/isolation & purification , Peristalsis/genetics , Probiotics/therapeutic use , RNA, Ribosomal, 16S/genetics , TranscriptomeABSTRACT
OBJECTIVE: To explore the clinical therapeutic effect of herb-partitioned moxibustion at fanwei point in patients of diabetic gastroparesis differentiated as spleen and stomach deficiency and retention of turbid dampness as well as its effect mechanism. METHODS: A total of 134 patients with diabetic gastroparesis were randomized into an observation group and a control group, 67 cases in each one. In the observation group, herb-partitioned moxibustion at fanwei point was adopted, 40 min each time, once a day for 5 times a week. In the control group, itopride hydrochloride tablets were prescribed for oral administration, 50 mg each time, three times a day. A total of 6 weeks of treatment was required in the two groups. Before and after treatment, the gastroparesis cardinal symptom index (GCSI) scores, 4-hour gastric emptying rate, TCM symptom score, as well as the levels of plasma motilin and serum gastrin were observed in the patients of the two groups. Additionally, the clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of every item of GCSI, TCM symptom scores and the levels of plasma motilin and serum gastrin were all reduced as compared with those before treatment in the patients of the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Regarding 4-hour gastric emptying rates, which were increased as compared with those before treatment in the two group (P<0.05), and the rate in the observation group was higher remarkably than that in the control group (P<0.05). The total effective rate was 92.5% (62/67) in the observation group, higher than 74.6% (50/67) in the control group (P<0.05). CONCLUSION: Herb-partitioned moxibustion at fanwei point relieves the clinical symptoms in the patients with diabetic gastroparesis and increases the gastric emptying rate, which is probably related to the regulation of the levels of plasma motilin and serum gastrin.
Subject(s)
Diabetes Mellitus , Gastrins/blood , Gastroparesis/therapy , Motilin/blood , Moxibustion , Acupuncture Points , Gastric Emptying , HumansABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .
Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Drugs, Chinese Herbal/therapeutic use , Intestine, Small/drug effects , Stress, Psychological/drug therapy , Animals , Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Biogenic Monoamines/metabolism , Brain/drug effects , Brain/metabolism , Chronic Disease , Cytokines/blood , Depression/blood , Depression/physiopathology , Drugs, Chinese Herbal/pharmacology , Gastrins/blood , Gastrointestinal Transit/drug effects , Glucagon-Like Peptide 1/blood , Intestine, Small/physiology , Male , Motilin/blood , Rats, Sprague-Dawley , Stress, Psychological/blood , Stress, Psychological/physiopathology , Substance P/blood , Vasoactive Intestinal Peptide/bloodABSTRACT
OBJECTIVE@#To explore the clinical therapeutic effect of herb-partitioned moxibustion at point in patients of diabetic gastroparesis differentiated as spleen and stomach deficiency and retention of turbid dampness as well as its effect mechanism.@*METHODS@#A total of 134 patients with diabetic gastroparesis were randomized into an observation group and a control group, 67 cases in each one. In the observation group, herb-partitioned moxibustion at point was adopted, 40 min each time, once a day for 5 times a week. In the control group, itopride hydrochloride tablets were prescribed for oral administration, 50 mg each time, three times a day. A total of 6 weeks of treatment was required in the two groups. Before and after treatment, the gastroparesis cardinal symptom index (GCSI) scores, 4-hour gastric emptying rate, TCM symptom score, as well as the levels of plasma motilin and serum gastrin were observed in the patients of the two groups. Additionally, the clinical therapeutic effect was evaluated in the two groups.@*RESULTS@#After treatment, the score of every item of GCSI, TCM symptom scores and the levels of plasma motilin and serum gastrin were all reduced as compared with those before treatment in the patients of the two groups (<0.05), and those in the observation group were lower than the control group (<0.05). Regarding 4-hour gastric emptying rates, which were increased as compared with those before treatment in the two group (<0.05), and the rate in the observation group was higher remarkably than that in the control group (<0.05). The total effective rate was 92.5% (62/67) in the observation group, higher than 74.6% (50/67) in the control group (<0.05).@*CONCLUSION@#Herb-partitioned moxibustion at point relieves the clinical symptoms in the patients with diabetic gastroparesis and increases the gastric emptying rate, which is probably related to the regulation of the levels of plasma motilin and serum gastrin.