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Inhibitory Effects of Cabbage Juice and Cabbage-Mixed Juice on the Growth of AGS Human Gastric Cancer Cells and on HCl-Ethanol Induced Gastritis in Rats
Abstract
This study determined the effects of cabbage juice and cabbage-mixed juices on the growth of AGS human gastric cancer cells and their anti-gastritic effects on HCl-ethanol induced gastritis in SD rats. Cabbage juice showed the highest growth inhibition on AGS gastric cancer cells in vitro (42%), compared with chlorella (20%) and kale juice (21%). However, cabbage-chlorella and cabbage-kale juice mixtures (at a 7:3 ratio) showed synergistic effects (57% and 65% inhibitory effects, respectively) on the gastric cancer cells. Inflammatory genes (iNOS, COX-2, TNF- and IL-) were significantly down-regulated in the mixed juices. Tests of DPPH radical scavenging activity and acid-neutralizing capacity with the mixed juices also showed this trend, as cabbage-chlorella and cabbage-kale mixed juices showed synergistic effects compared to cabbage juice alone. The inhibition rate of acute gastritis induced by HCl-ethanol in rats was 46% with high amounts of cabbage (CH; 800 mg/kg), 71% with high amounts of cabbage and chlorella (CChH; 800 mg/kg), 74% with high amounts of cabbage and kale (CKH; 800 mg/kg), and 75% with cimetidine (positive control) compared with the control. In addition, rates with CChH and CKH showed decreasing gastric secretions with increasing pH. These results show that cabbage juice and cabbage-mixed juices, especially with chlorella or kale, exhibit remarkable anti-gastritic effects and can be administered for a long period for the prevention and treatment of gastric cancer and gastritis.
... Therefore, the development of therapeutic agents for gastritis and gastric ulcers using natural products, with no side effects, is in progress. Several studies have recently reported the protective effects of natural products without side effects and toxicity against gastric mucosal damage using several animal models [9,11,12]. ...
... The rats were given ad libitum access to feed and water. In experiments for inducing gastric ulcers, mice were administered their respective C. cassia extract article (except for the gastritis control groups, which were administered a carboxymethyl cellulose sodium salt (CMC) solution) after 48 h of feed deprivation, and gastric damage was induced by administering indomethacin (80 mg/kg) [51,52], ethanol (100% EtOH), or an ethanol-HCl (150 mM HCl in 70% EtOH) [11,12] ...
... This study was approved by the Institutional Animal Care and Use Committee (INHA130307-196, approved on 7 March 2013). Mice fasted for 48 h, and then C. cassia extract articles were administered 30 min before the HCl/EtOH mixture (150 mM HCl in 70% EtOH) induced acute gastric damage [11,12]. After 1 h, the pylorus was ligated, and the stomachs were removed after 4 h. ...
Gastritis is a common disease worldwide that is caused by various causes such as eating habits, smoking, severe stress, and heavy drinking, as well as Helicobacter pylori infections and non-steroidal anti-inflammatory drugs. Cinnamomum cassia is a tropical aromatic evergreen tree commonly used as a natural medicine in Asia and as a functional food ingredient. Studies have reported this species’ anti-obesity, anti-diabetic, and cardiovascular disease suppression effects. We evaluated the potential effects of C. cassia using non-steroidal anti-inflammatory drugs (NSAIDs), ethanol (EtOH), and ethanol/hydrochloric acid (HCl)-induced gastric mucosal injury models. C. cassia extracts reduced the area of gastric mucosa injury caused by indomethacin, NSAID, EtOH, and EtOH/HCl. We also applied a network pharmacology-based approach to identify the active compounds, potential targets, and pharmacological mechanisms of C. cassia against gastritis. Through a network pharmacology analysis, 10 key components were predicted as anti-gastritis effect-related compounds of C. cassia among 51 expected active compounds. The NF-κB signaling pathway, a widely known inflammatory response mechanism, comprised a major signaling pathway within the network pharmacology analysis. These results suggest that the anti-gastritis activities of C. cassia may be induced via the anti-inflammatory effects of key components, which suppress the inflammation-related genes and signaling pathways identified in this study.
... Therefore, development of new drugs to treat gastritis and gastric ulcers using natural plants or herbs which have no toxicity and side effects is promising. Recently, the protective effects of herbal extracts against gastric injuries such as the protective effects of Lycium chinense Miller (Solanaceae) on acute gastric lesion in mice (Lee et al. 2015) and inhibitory effects of cabbage juice on EtOH-HCl induced gastritis in rats (Hong et al. 2013) were reported. ...
... The NSAID indomethacin-induced bleeding, ulcers, and erosions in the gastrointestinal tract in both animal and human trials (Djahanguiri 1969). In addition, EtOH/HCl causes severe damage and necrotic lesions to the gastric mucosa (Hong et al. 2013). The animal models of gastric injuries induced by indomethacin and EtOH/HCl have been widely used in studies to evaluate the protective effects of herbal products against gastritis and gastric ulcers. ...
Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted.
Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated.
Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg⁻¹, and cimetidine 100 mg kg⁻¹, respectively. Indomethacin (80 mg kg⁻¹) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining.
Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg⁻¹; 64.30% and 67.75%, p < 0.001) compared to indomethacin group. In the EtOH/HCl-induced model, HemoHIM reduced gastric lesion (250 and 500 mg kg⁻¹; 61.05% and 73.37%, p < 0.001) and gastric acidity (250 and 500 mg kg⁻¹; 37.80 and 45.20 meq L⁻¹, p < 0.001) compared to EtOH/HCl group. H&E staining of the gastric mucosa showed decreased erosion and hemorrhage in HemoHIM group compared to EtOH/HCl group.
Discussion and conclusions: Based on the results, HemoHIM is potential candidate for the treatment of gastritis and gastric ulcers.
White cabbage (Brassica oleracea var. capitata) reportedly exerts antioxidant, anti-inflammatory, and anti-gastric effects. We aimed to evaluate the biological activity of B. oleracea fermented with Lactobacillus plantarum (FBO). The plant material was fermented for 7 d. The antioxidative potentials of FBO (DPPH radical-scavenging activity, and total phenol and total flavonoid contents) and ability of FBO to inhibit digestive enzymes (α-amylase and lipase) were tested. Anti-inflammatory and anti-allergic effects were also determined by measuring the release of NO, inflammatory cytokines (IL-1β, TNF-α and IL-4), β-hexosaminidase and histamine. FBO contained 15.84±0.25 mg GAE/g phenols and 1.19±0.09 mg NA/g flavonoids. FBO showed DPPH radical-scavenging activity, and inhibited α-amylase and lipase. It also inhibited of NO, PGE2 and inflammatory cytokine production by LPS-stimulated RAW 264.7 macrophages. Finally, FBO inhibited degranulation and inflammatory cytokine production in antigen-stimulated RBL-2H3 mast cells, in a dose-dependent manner. Collectively, these observations indicate that white cabbage fermented with L. plantarum can be used as a functional material and edible resource in industrial setting.
Extracts from spinach, cabbage, and onion are known to possess various instructive characteristics, including antioxidant and anti-inflammation activities. Spinach, cabbage, and onion are consumed worldwide and represent important sources of dietary phytochemicals with proven antioxidant properties, such as flavonoids and phenolic acids. Food-derived flavonoids and phenolic compounds are expected to be promising drugs for cancer. In the present study, we investigated the effects of methanol extracts of spinach, cabbage, and onion on cell proliferation and apoptosis in human gastric and breast cancer cells. Proliferation rates of AGS, MDA-MB-231, and SK-BR-3 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The methanol extracts of spinach, cabbage, and onion inhibited proliferation of cancer cells in a dose-dependent manner. 4',6-Diamidino-2-phenylindole (DAPI) staining revealed that chromatin condensation significantly increased compared with the control. In the results of MTT assay and DAPI staining, onion extract was the most effective in inhibiting cancer cell proliferation and apoptosis. To assess changes in protein expression level by onion extract, we identified Bax (pro-apoptotic), Bcl-2 (anti-apoptotic), and poly(ADP-ribose) polymerase (PARP) protein by western blot analysis. The expression of Bax and cleaved-PARP increased, whereas expression of Bcl-2 was decreased compared with the control. These results suggest that spinach, cabbage, and onion extracts suppressed growth of human gastric cancer AGS, human breast cancer MDA-MB-231, and SK-BR-3 cells through induction of apoptosis. Among the extracts, onion extract had stronger anti-cancer and apoptosis induction effects than spinach and cabbage extracts. Further, onion extract more effectively induced apoptosis of human gastric cancer cells than human breast cancer cells. Therefore, further studies are needed to determine the anti-cancer effects of onion extracts in vivo. Onion extract can be developed as a chemopreventive or therapeutic agent for gastric cancer. © 2016, Korean Society of Food Science and Nutrition. All rights reserved.
This study was carried out to investigate antioxidative and antimicrobial activities of ethanol extracted garlic stem and red cabbage, and their application to pork patties during refrigerated storage. Total phenolic compounds of ethanol extracted garlic stem and red cabbage were 3.13 g/100 g and 3.99 g/100 g, respectively. 1,1'-diphenyl-2-picryhdrazyl (DPPH) radical scavenging activity of garlic stem extracts increased up to 0.05%. Iron chelating activities of both garlic stem and red cabbage increased up to 0.5%, and red cabbage up to the concentration of 1% had similar iron chelating activity to those of EDTA. Pork patties containing garlic stem had higher Hunter L and b values, (p0.05). Thiobarbituric acid reactive substances (TBARS) of pork patties with garlic stem were lower than those of the control (p
Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses of 0, 5, 30, or 75 microg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects of once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH( 1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75-microg/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.
An elevated LDL-cholesterol concentration is associated with an increased risk of cardiovascular disease. The association between fruit and vegetable consumption and LDL has been inconsistent.
The objective was to determine whether a high intake of fruit and vegetables is inversely associated with LDL concentrations.
We used data collected from 4466 subjects in the National Heart, Lung, and Blood Institute Family Heart Study to study the association between fruit and vegetable consumption and serum LDL. We used a food-frequency questionnaire to assess fruit and vegetable intakes and regression models to estimate adjusted mean LDL according to fruit and vegetable consumption.
The mean (+/-SD) age of the men (n = 2047) was 51.5 +/- 14.0 y and that of the women (n = 2419) was 52.2 +/- 13.7 y. The average daily serving of fruit and vegetables was 3.2 +/- 1.7 for men and was 3.5 +/- 1.8 for women. Fruit and vegetable consumption was inversely related to LDL: in the categories 0-1.9, 2.0-2.9, 3.0-3.9, and > or = 4 servings/d, multivariate-adjusted mean (95% CI) LDL concentrations were 3.36 (3.28, 3.44), 3.35 (3.27, 3.43), 3.26 (3.17, 3.35), and 3.17 (3.09, 3.25) mmol/L, respectively, for men (P for trend < 0.0001) and 3.35 (3.26, 3.44), 3.22 (3.14, 3.30), 3.21 (3.13, 3.29), and 3.11 (3.04, 3.18), respectively, for women (P for trend < 0.0001). This association was observed across categories of age, education, smoking status, physical activity, and tertiles of Keys score. Exclusion of subjects with prevalent diabetes mellitus or coronary artery disease did not alter these results significantly.
Consumption of fruit and vegetables is inversely related to LDL in men and women.
The aim of our study is to evaluate the relationship between diet and cancer development. It has been estimated that 30-40% of all kinds of cancer can be prevented with a healthy lifestyle and dietary measures. A low use of fibres, the intake of red meat and an imbalance of Omega-3 and Omega-6 fats may contribute to increase the risk of cancer. On the other hand, the assumption of lots of fruit and vegetables may lower the risk of cancer. Protective elements in a cancer-preventive diet include selenium, folic acid, vitamin B12, vitamin D, chlorophyll and antioxidants such as carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits if taken orally, but it effective through intravenous injection. A supplementary use of oral digestive enzymes and probiotics is also an anticancer dietary measure. A diet drawn up according to the proposed guidelines could decrease the incidence of breast, colon-rectal, prostate and bronchogenic cancer.
This article reviews the mechanisms by which glucosinolate breakdown products are thought to inhibit carcinogenesis. It describes how isothiocyanates, thiocyanates, nitriles, cyano-epithioalkanes and indoles are produced from glucosinolates through the actions of myrosinase, epithiospecifier protein and epithiospecifier modifier protein released from cruciferous vegetables during injury to the plant. The various biological activities displayed by these phytochemicals are described. In particular, their abilities to induce cytoprotective genes, mediated by the Nrf2 (NF-E2 related factor 2) and AhR (arylhydrocarbon receptor) transcription factors, and their abilities to repress NF-kappaB (nuclear factor-kappaB) activity, inhibit histone deacetylase, and inhibit cytochrome P450 are outlined. Isothiocyanates appear to alter gene expression through modification of critical thiols in regulatory proteins such as Keap1 (Kelch-like ECH-associated protein 1) or IKK (IkappaB kinase), causing activation of Nrf2 and inactivation of NF-kappaB, respectively. Certain indoles act as ligands for AhR. Isothiocyanates and indoles are also capable of affecting cell cycle arrest and stimulating apoptosis. The mechanisms responsible for these anti-proliferative responses are discussed.
In this study, we determined total polyphenol content(TPC) and total flavonoid content(TFC) of extracts from Korean cabbage and cabbage using a spectrophotometric method as well as glucosinolates concentration by HPLC. TPCs of Korean cabbage and cabbage extracts were 308.48 ?g GAE/g dry weight and 344.75 ?g GAE/g dry weight, respectively. TFCs of Korean cabbage and cabbage extracts were 5.33 ?g QE/g dry weight and 5.95 ?g QE/g dry weight, respectively. We found six different glucosinolates, namely progoitrin, glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin and 4-methoxyglucobrassicin in the Korean cabbage extract. In the cabbage extract, there was four glucosinolates, namely glucoraphanin, sinigrin, glucobrassicin and 4-methoxyglucobrassicin. We determined the cytotoxic effect of Korean cabbage and cabbage extracts in AGS human stomach cancer cells, HepG2 human hepatic cancer cells and LNCaP human prostate cancer cells by MTT assay. Dose-dependent relationships were found between the extract concentrations and cancer cell growth inhibition. The overall results support that both Korean cabbage and cabbage, the major vegetables in Korea, contain bioactive compounds such as polypheol, flavonoids as well as glucosinolates and they may play a positive role in cancer prevention.
Glycyrrhizae Radix, the dried roots of Glycyrrhiza glabra or Glycyrrhiza uralensis Fischer(Legumino-sae), has been used as a medicine for treatment of imflammation, arthritis, respiratory ailment, skin diseases and liver problems. The purpose of this study was to examine the effect of 70% ethanol extract, 18-{\beta}-glycyrrhetinic acid, glycyrol and carbenoxolone disodium from Glycyrrhizae Radix on gastritis and gastric cancer. Using these materials, we tested antibacterial activity against Helicobacter pylori, antigastritic activity for HCI-ethanol-induced gastric lesion and the pylorus ligated gastric secretion with rats, and cell viability in gastric cancer cell. 18-{\beta}-glycyrrhetinic acid and carbenoxolone disodium decreased the volume of gastric secretion and acid output in pylorus ligated rats. Also, carbenoxolone disodium had a strong effect of antibacterial activity on H. pylori. In addition 18-{\beta}-glycyrrhetinic acid and glycyrol reduced cell viability in human gastric cancer cells(AGS and SNU638 cell) in dose-dependent manner. The reduction of total acid output and gastric secretion as well as the anti-bacterial activity against H. pylori might account for the antigastritic effects of carbenoxolone disodium.
The purpose of this study was to investigate the effects of green vegetable (kale) juice powder supple-mentation on lipid profiles, plasma homocysteine, folate and vitamin in rats fed cholesterol (Chol. ) or Chol. free diet. 7-week old male Sprague Dawley rats (n=40) were divided into 4 groups, and experimental diets containing control diet group (CO), control diet plus 0.5 wt Chol. (CC), control diet added with 5 wt kale (KO), control diet added with 5 wt kale plus 0.5 wt Chol. (KC) were fed for 8 wks. Plasma homocysteine level was examined by amino acid analyzer and serum folate and vitamin level were measured by com-petitive radioimmunoassay methods. In various serum lipid profiles, TG level was lower in kale juice powder groups (KO, KC) compared to the corresponding groups (CO, CC) (p
The intensity of electroluminescence (EL) and its spectrum were studied as a function of generation rate, temperature, and intrinsic-layer thickness in a group of hydrogenated amorphous silicon p-i-n diodes (p = p-type, i = intrinsic, and n = n-type). It was found that: (a) the electroluminescence efficiency is as high as the photoluminescence efficiency; (b) there is a power-law dependence of the total EL intensity versus forward current density, except in the low-injection regime; (c) the defect luminescence is mainly a p-i junction effect, but the main band luminescence is a true i-layer bulk effect that is observed in thick samples at room temperature.
The quercetin and kaempferol contents of 13 varieties of lettuce were determined. Leaf lettuce varieties contained 2-54 mg of quercetin/kg, while head lettuce varieties contained 1-28 mg/kg, more in the outer leaves than in the inner leaves. These samples also contained 0-2 mg of kaempferol/kg. Chives contained 55 mg of kaempferol and 9 mg of quercetin per kg in green portions and lesser amounts in white portions, while leek contained 20 mg of kaempferol/kg in green portions and no detectable quercetin in either portion. Two varieties of kale contained 7-20 mg of quercetin and 13-30 mg of kaempferol per kg. Other vegetables examined contained lesser amounts of these flavonols. No myricetin was detected in these samples.
A case-control study focusing on the role of single food items was undertaken in the Heilongjiang area, 241 patients with histologically verified stomach cancer and an equal number of controls (with non-neoplastic diseases) matched by age, sex and area of residence being interviewed during a 2-year period. Questions asked covered economic status, occupation, histories of smoking and drinking, diet and dietary habits and disease history. Data concerning the average frequency and quantity of consumption of single food items were obtained by the same interviewer. An inverse association between the consumption of vegetables and stomach cancer was observed whereas high intake of potatoes and of salted and fermented soya paste appeared to be high-risk factors. Specifically, Chinese cabbage plays an important role in reducing the risk of developing stomach cancer.
Cabbage is an important source of dietary antioxidants, available throughout the year. Using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry we studied changes in antioxidant compounds in white cabbage during 6 months of commercial storage. Cabbages were harvested at the end of November and stored until the end of May in pallet bins in a refrigerated shed under natural-air conditions. Samples were collected four times during storage in November, February, April and May. Antioxidant compounds identified in cabbage included: ascorbic and dehydroascorbic acid (vitamin C), pyridoxine and pyridoxamine (vitamin B6), nicotinamide and nicotinic acid (vitamin B3), pantothenic acid (vitamin B5); flavonoids (artemetin, betanidin, butein/naringenin chalcone, chalcone, cyanidin, equol, flavone, hydroxyflavone, kaempferol/luteolin, malvidin, naringenin/tetrahydrochalcone, nobiletin, pelargonidin, purpurogallin and quercitol); phenolic acids (benzoic, caffeic, cinnamic, coumaric/hydroxycinnamic, dimethoxybenzoic, gallic/trihydroxybezoic, phenylacetic, rosmarinic, syringic, vanillic and veratric). Fresh-harvested cabbages contained the highest levels of ascorbic acid and pyridoxine. Vitamins B3 and B5 and D2 were below the detection limit. During the first 3 months of storage cabbage lost all pyridoxamine and ∼80% of ascorbic acid. At the end of storage, however, the content of ascorbic acid and vitamins B3 and B5 increased, which may reflect preparation of cabbage for a new growth. A large variety of flavonoids were present in fresh-harvested cabbages. More than half of these compounds were lost during the first 5 months of storage. However, at the end of storage an increase in the levels of some flavonoids was detected. Among 11 phenolic acids found in this study, 7 compounds were present during all the storage period, 2 compounds were lost and 3 other compounds appeared during storage. Starting from April, the appearance of dark lesions on the outer cabbage leaves and detection of ergosterol in cabbage samples indicated the progression of fungal infection. This could trigger synthesis of flavonoids and phenolic acids associated with pathogen resistance in the last months of storage. The study demonstrates that changes in antioxidant compounds in cabbage during long-term storage reflect several ongoing processes, such as postharvest senescence, biennial cycle and response to fungal infection.
The anticancer activity of sulforaphane is known to be mediated at least partly by apoptosis induction and associated with the presence of the -N=C=S moiety. The present study explored how oxidation of sulphur in the side chain of sulforaphane affected apoptosis induction to provide the chemical basis of sulforaphane effects. Sulforaphane analogues containing oxidised sulphur (alyssin, sulforaphane, erysolin and alyssin sulfone) exerted a superior growth inhibitory effect compared with sulforaphane analogues with nonoxidised sulphur (erucin and berteroin) in human colon cancer cell lines. Furthermore, erysolin was a more potent inducer of reactive oxygen species (ROS) and apoptosis compared with erucin. Erysolin-induced ROS generation and subsequent apoptosis were inhibited by pretreatment with the antioxidant N-acetyl-cysteine. Erysolin induced caspase-8 activation, while blockade of caspsase 8 activation inhibited apoptosis induced by erysolin. Taken together, sulforaphane analogues with oxidised sulphur were the most efficient apoptosis inducers, likely due to high-level ROS induction.
The content of the potentially anticarcinogenic flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin of 28 vegetables and 9 fruits was determined by RP-HPLC with UV detection. Fresh foods were purchased in a supermarket, agrocery, and a street market and combined to composites. Processed foods were purchased additionally. Sampling was carried out in spring, summer, winter, and spring of the following year. Quercetin levels in the edible parts of most vegetables were generally below 10 mg/kg except for onions (284-486 mg/kg), kale (110 mg/kg), broccoli (30 mg/kg), French beans (32-45 mg/kg), and slicing beans (28-30 mg/kg). Kaempferol could only be detected in kale (211 mg/kg), endive (15-91 mg/kg), leek (11-56 mg/kg), and turnip tops (31-64 mg/kg). In most fruits the quercetin content averaged 15 mg/kg, except for different apple varieties in which 21-72 mg/kg was found. The content of myricetin, luteolin, and apigenin was below the limit of detection (
Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.
Benzyl isothiocyanate and phenethyl isothiocyanate, two compounds found in cruciferous plants, and phenyl isothiocyanate, a synthetic compound, all inhibit 7,12-dimethylbenz[a]anthracene (CMBA)-induced mammary tumor formation in female Sprague-Dawley rats when administered 4 hours prior to the DMBA. Comparable studies in which benzyl isothiocyanate was administered 24 hours before or 4 hours after DMBA showed almost complete loss of inhibition. Additions of benzyl isothiocyanate or phenethyl isothiocyanate to a diet containing CMBA inhibited formation of neoplasms of the forestomach and pulmonary adenomas in female ICR/Ha mice. Addition of benzyl isothiocyanate to a diet containing benzo[a]pyrene also inhibited carcinogenesis of the mouse forestomach due to this carcinogen. The finding of two additional anutrient dietary compounds which inhibit chemical carcinogenesis focuses on the possibility that dietary constituents of this nature may diminish the impact of exposures to chemical carcinogens.
Cysteamine was previously found to produce duodenal ulcers in rats. In the present study, the effect of cysteamine on gastric secretion was studied. Cysteamine administered by a parenteral or intraduodenal route induced a marked and sustained increase in gastric secretion in conscious and in anesthetized rats. The response to cysteamine or its metabolite, cystamine, appeared gradually and the maximum response was observed in 2 or 3 hr after the administration. The response to cysteamine was completely inhibited by vagotomy and inhibited dose-dependently by atropine methylbromide or hexamethonium. Cysteamine stimulated gastric acid secretion in conscious rats with chronic gastric fistula but not in rats with denervated gastric pouch. Tissue histamine levels in the gastric mucosa, abdominal muscle and whole blood were not affected by cysteamine. These results suggest that a cholinergic mechanism is involved in the gastric secretion induced by cysteamine.
Concentrated ethanol causes gastric lesions by a mechanism that is poorly understood. We have investigated this mechanism in the rat stomach via gross morphologic, videomicroscopic, histochemical, and pharmacologic approaches. Within 1 min of contact, ethanol caused diffuse mucosal hyperemia. By 5 min, hyperemia greatly intensified at some mucosal sites. Beneath sites where mucosal hyperemia developed, intramural venules strongly constricted at 3-13 s postethanol, whereas submucosal arterioles dilated more than two times in diameter by 25 s. Submucosal venular constriction began sooner than arteriolar dilation (9 vs. 16 s, p less than 0.05). One-third of the gastric mucosal mast cells degranulated by 15 s postethanol; 50% discharged by 30 s. Ethanol-induced hyperemia was markedly reduced by lipoxygenase-selective inhibitors BW755C or nordihydroguaiaretic acid, or by the H1-antihistamine pyrilamine, but not by indomethacin, cimetidine, phentolamine, or methysergide. Based on these results, a model for the pathogenesis of ethanol-induced gastric lesions is proposed.
The participation of polyamines and nonprotein sulfhydryls in the gastric cytoprotective mechanisms was studied using gastric mucosal lesions produced by acidified ethanol in rats as an experimental model. Treatment with prostaglandin E2 (PGE2), but not cimetidine, prevented the formation of gastric mucosal lesions. Oral administration of cadaverine, spermidine and spermine prevented the lesion formation by acidified ethanol in a dose-dependent manner. Indomethacin or acetazolamide had no influence on the cytoprotective effect of spermine, whereas sulfhydryl blockers such as iodoacetamide and N-ethylmaleimide partially blocked it. Sulfhydryl compounds such as cysteine, reduced glutathione (GSH), and cysteamine prevented the lesion formation induced by acidified ethanol. The concentration of nonprotein sulfhydryls in the gastric mucosa was significantly decreased at 1 hr after administration of acidified ethanol, and this decrease was partially prevented by spermine or PGE2. These results suggest that the cytoprotective effect of spermine may not be mediated by endogenous prostaglandins or alkaline secretion in the gastric mucosa, but may be partially related to endogenous sulfhydryl compounds.
We previously demonstrated calcitonin gene-related peptide (CGRP) immunoreactivity in sensory nerves in the rat uterus and that CGRP inhibits stimulated uterine contraction in vitro. The present study was undertaken to: 1) examine possible roles nitric oxide (NO) may have in the inhibitory action of CGRP on uterine contraction and 2) identify sites where NO may be synthesized. The relaxing effect of CGRP on SP-stimulated uterine contraction was established in vitro on uterine horns from diethylstilbestrol-treated rats. These experiments were repeated with or without an arginine analog [NG-monomethyl-L-arginine (L-NMMA)] that inhibits NO formation. The localization of the synthetic enzyme for NO production, NO synthase, was accomplished by histochemically staining for NADPH-diaphorase. Calcitonin gene-related peptide (10(-7) M) significantly reduced SP (10(-5) or 10(-6) M)-stimulated uterine contraction. The L-NMMA (10(-3) M) blocked the relaxing action of CGRP on SP-stimulated uterine contraction. The L-NMMA alone had no effect on SP-stimulated uterine contraction. NADPH-diaphorase-positive nerve fibers were located in the myometrium, endometrium, and adjacent to the vasculature. These data demonstrate that: 1) L-NMMA suppresses the relaxant effect of CGRP on myometrial activity and 2) NADPH-diaphorase (indicative of NO synthase) is localized in uterine nerve fibers. These data suggest that the inhibitory action of CGRP may be dependent on NO formation and that the enzyme necessary for NO production is present in nerves in areas optimal to affect myometrial activity.
We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria-specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5. To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1 alpha, IL-12, GM-CSF, MIP and TNF alpha genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of gamma IFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of gamma IFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment THI responses against Listeria via activation of macrophages to produce IL-12 and enhance host defence against Listeria infection both in normal and MAIDS mice.
Extracts of acidified human gastric fundic mucosa have been fractionated on diethylaminoethyl cellulose to yield three pepsin fractions, which have, in order of their elution, been attributed to pepsin I, pepsin II A, and a mixture of pepsin II B and pepsin III. Acidification of previously purified pepsinogen I and pepsinogen III yields pepsin I and pepsin III, respectively. Acidification of previously purified pepsinogen II yields two distinct pepsin fractions, pepsin II A and pepsin II B. Pepsin II B and pepsin III have the same chromatographic mobility on diethylaminoethyl cellulose, but are probably not identical. Pyloric and duodenal mucosa yield only pepsin I upon acidification. Human pepsin-pepsin inhibitor complex is demonstrable as a chromatographic fraction distinct from pepsins upon fractionation of acidified dilute pepsinogen solutions with diethylaminoethyl cellulose equilibrated with acetate buffer pH 5.3.
Twenty-eight polyphenols (11 flavonoid derivatives and 17 hydroxycinnamic acid derivatives) were detected in different cultivars of the Chinese cabbage pak choi ( Brassica campestris L. ssp. chinensis var. communis) by HPLC-DAD-ESI-MS(n). Kaempferol was found to be the major flavonoid in pak choi, glycosylated and acylated with different compounds. Smaller amounts of isorhamnetin were also detected. A structural determination was carried out by (1)H and (13)C NMR spectroscopy for the main compound, kaempferol-3-O-hydroxyferuloylsophoroside-7-O-glucoside, for the first time. Hydroxycinnamic acid derivatives were identified as different esters of quinic acid, glycosides, and malic acid. The latter ones are described for the first time in cabbages. The content of polyphenols was determined in 11 cultivars of pak choi, with higher concentrations present in the leaf blade than in the leaf stem. Hydroxycinnamic acid esters, particularly malic acid derivatives, are present in both the leaf blade and leaf stem, whereas flavonoid levels were determined only in the leaf blade.
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(2012년 12월 7일 접수; 2013년 2월 20일 채택)
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