The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150-200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2.
Helicobacter pylori have been shown to influence physiological regulation of metabolic hormones involved in food intake, energy expenditure and body mass. It has been proposed that inducing H. pylori-induced gastric atrophy damages hormone-producing endocrine cells localized in gastric mucosal layers and therefore alter their concentrations. In a recent study, we provided additional proof in mice under controlled conditions that H. pylori and gut microbiota indeed affects circulating metabolic gut hormones and energy homeostasis. In this addendum, we presented data from follow-up investigations that demonstrated H. pylori and gut microbiota-associated modulation of metabolic gut hormones was independent and precedes H. pylori-induced histopathological changes in the gut of H. pylori-infected mice. Thus, H. pylori-associated argumentation of energy homeostasis is not caused by injury to endocrine cells in gastric mucosa.
Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.
The aim of this study was to investigate if colloidal bismuth subcitrate (CBS) can penetrate the gastric mucus barrier to reach the different sites of the antral mucosa and to estimate the time course for CBS to reach and remain in the mucosa. A single dose of CBS was administered orally to rats that were sacrificed at different time intervals post treatment. The control group received gum acacia without CBS. Colloidal bismuth subcitrate, visualised as electron dense precipitate (EDP), was seen in the gastric mucus layer, intercellular spaces and intracellularly after 30 minutes and disappeared after 6 hours. Scant amounts of EDP were observed in the gastric crypts, confined only to the upper parts of these structures. We concluded that CBS can penetrate the mucus and has a wide but uneven distribution in the gastric mucosa. Colloidal bismuth subcitrate, in the concentration given only penetrated the upper two-thirds of gastric pits and not the lower one-third. We also concluded that CBS has to be given 6 hourly to ensure its continuous presence in the gastric mucosa.
We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2.
Novel diethanolamine-grafted high-methoxyl pectin (DGP)-arabic gum (AG) modified montmorillonite (MMT) composites were developed for intragastric ziprasidone HCl (ZIP) delivery by combining floating and mucoadhesion mechanisms. The ZIP-loaded clay-biopolymer matrices were accomplished by ionotropic gelation protocol utilizing zinc acetate in the presence or absence of covalent crosslinker, glutaraldehyde (GA). Various formulations exhibited excellent drug entrapment efficiency (DEE, %) and sustained drug release profiles, which were influenced by the polymer-blend (DGP:AG) ratios, reinforcing filler (MMT) existence and crosslinking procedure. The optimal composites (F-3) demonstrated DEE of 61% and Q8h of 52% with outstanding buoyancy, mucin adsorption ability and biodegradability. The release profile of F-3 was best fitted in the Korsmeyer-Peppas model with Fickian diffusion driven mechanism. The mucin adsorption to composites F-3 followed Freundlich isotherms. The molar mass between crosslinks of composites (F-3) calculated employing Flory-Rehner equation was increased with temperature. Moreover, the thermal, X-ray and infrared analyses confirmed a compatible environment of drug in the composites, except certain extent of transformation of the crystalline drug to its amorphous form. The SEM studies revealed the spherical morphology of the composites. Thus, the newly developed DGP-AG-MMT composites are appropriate for gastroretentive ZIP delivery over an extended period of time.
Chronic atrophic gastritis (CAG) is a common gastrointestinal disease which has been considered as precancerous lesions of gastric carcinoma. Previously, electro-acupuncture stimulation has been shown to be effective in ameliorating symptoms of CAG. However the underlying mechanism of this beneficial treatment is yet to be established. In the present study, an integrated histopathological examination along with molecular biological assay, as well as 1H NMR analysis of multiple biological samples (urine, serum, stomach, cortex and medulla) were employed to systematically assess the pathology of CAG and therapeutic effect of electro-acupuncture stimulation at Sibai (ST 2), Liangmen (ST 21), and Zusanli (ST 36) acupoints located in the stomach meridian using a rat model of CAG. The current results showed that CAG caused comprehensive metabolic alterations including the TCA cycle, glycolysis, membrane metabolism and catabolism, gut microbiota-related metabolism. On the other hand, electro-acupuncture treatment was found able to normalize a number of CAG-induced metabolomics changes by alleviating membrane catabolism, restoring function of neurotransmitter in brain and partially reverse the CAG-induced perturbation in gut microbiota metabolism. These findings provided new insights into the biochemistry of CAG and mechanism of the therapeutic effect of electro-acupuncture stimulations.
Acupuncture is a traditional Chinese medicine therapy that has been found useful for treating various diseases. The treatments involve the insertion of fine needles at acupoints along specific meridians (meridian specificity). This study aims to investigate the metabolic basis of meridian specificity using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Electro-acupuncture (EA) stimulations were performed at acupoints of either Stomach Meridian of Foot-Yangming (SMFY) or Gallbladder Meridian of Foot-Shaoyang (GMFS) in healthy male Sprague Dawley (SD) rats. 1H-NMR spectra datasets of serum, urine, cortex, and stomach tissue extracts from the rats were analysed by multivariate statistical analysis to investigate metabolic perturbations due to EA treatments at different meridians. EA treatment on either the SMFY or GMFS acupoints induced significant variations in 31 metabolites, e.g., amino acids, organic acids, choline esters and glucose. Moreover, a few meridian-specific metabolic changes were found for EA stimulations on the SMFY or GMFS acupoints. Our study demonstrated significant metabolic differences in response to EA stimulations on acupoints of SMFY and GMFS meridians. These results validate the hypothesis that meridian specificity in acupuncture is detectable in the metabolome and demonstrate the feasibility and effectiveness of a metabolomics approach in understanding the mechanism of acupuncture.
Curcuma purpurascens BI. is a medicinal plant from the Zingiberaceae family, which is widely used as a spice and as folk medicine. The aim of the present study is to investigate the gastroprotective activity of C. purpurascens rhizome hexane extract (CPRHE) against ethanol- induced gastric ulcers in rats.
A central composite design was applied to design a novel gastric floating drug delivery system comprising propranolol HCl in Terminalia catappa gum and to evaluate the buoyancy, in vitro drug release behavior, and pharmacokinetic parameters. All formulations exhibited good buoyancy properties in vitro reflected by floating lag time of 1-110 sec, total floating time of 9-16 h and prolonged release behaviour (upto 12 h). Statistically optimised formulation (PBGRso) was orally administered to human volunteers under both fasted and fed conditions to evaluate gastric floating behavior under different food conditions by X-ray evaluation. In vivo studies of optimised formulations revealed that the gastric residence time of floating tablets was enhanced in the fed but not in the fasted state. Pharmacokinetic studies of the optimised Terminalia catappa formulation and a commercial product (Ciplar LA 80) carried out on healthy human volunteers showed a significant improvement in the bioavailability (132%) of propranolol HCl released from from the experimental Terminalia catappa formulations compared with Ciplar LA 80.
1. Oral administration of [14C]histamine induced the presence of small amounts of [14C]histamine in stomach and ileal tissues of control guinea-pigs. In contrast, much larger amounts were found after 8 h infusion. 2. Similar amounts of [14C]histamine were found in the tissues when [14C]histamine was given by intravenous infusion from 24-30 h after chlorpromazine injection.
Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200 mg L-1); G3 was given leptin and MNNG. Rats were euthanized after 40 weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher's exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p gastric cancer requires further scrutiny.
Corchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats.
This study investigates the effects of tocotrienol (TT) or alpha-tocopherol (TF) supplementation on corticosterone level, noradrenalin level and gastric lesions in rats exposed to restraint stress. Twenty-four male Sprague Dawley rats were randomly assigned into 4 equally sized groups; two control groups were given olive oil, while the treated group was supplemented with either tocotrienol of tocopherol orally at a dose of 60 mg/kg body weight. After 28 days of treatment, one control group, TT group and TF group were subjected to restraint stress, 2 hours daily for 4 consecutive days. After the last exposure to stress, plasma samples were taken to determine the corticosterone and noradrenalin levels, after which the rats were sacrificed. The stomach was excised for the evaluation of gastric lesions. Our findings showed that TT and TF were able to maintain the corticosterone level to the prestress values, while only TT was able to maintain the noradrenalin level in rats exposed to stress. Tocotrienol was found to be better in preventing formation of gastric lesions compared to TF. As a conclusion, the protective effect of vitamin E was related to the ability to inhibit stress induced elevation of corticosterone and noradrenalin levels.
The effect of palm vitamin E on the healing of ethanol-induced gastric lesions and various biochemical parameters were investigated. The study was divided into two phases. In the first phase of the study, 42 rats of Sprague Dawley species (200-250 gm weight) were randomly divided into two groups fed with a normal diet (control) or palm vitamin E enriched diet (150 mg/kg) for 3 weeks. The rats were killed after 3 weeks of feeding. Gastric tissue contents of malondialdehyde (MDA), prostaglandin E2 and acid were measured. In the second phase of the study 42 rats were divided into two groups. Group 1 was fed normal rat pellets (control) and group 2 was fed palm vitamin E enriched pellets (150 mg/kg food) for 3 weeks. After 3 weeks of feeding gastric mucosal injury was induced by an orogastric tube administration of 0.5 ml 100% ethanol. The rats were killed at 1 hour, 4 hours and 1 week after ethanol exposure for semiquantitative determination of ulcer index and gastric acid concentration. Gastric tissue MDA and mucus were measured only at 1 week after ethanol exposure. In the first phase of the study we found that palm vitamin E only caused a significant reduction in gastric MDA. However, it showed no significant effects on prostaglandin E2 and gastric acid concentration. In the second phase of the study, the mean ulcer index of palm vitamin E supplemented group killed after 1 week of ethanol exposure was significantly lower compared to the respective control. However, there was no significant difference in ulcer index in rats killed at 1 hour and 24 hours after ethanol exposure. The gastric acid concentration was significantly higher in the group treated with palm vitamin E killed 1 week after ethanol exposure compared to control. The gastric tissue MDA was significantly lower in the palm vitamin E supplemented group compared to control. There was no significant difference in gastric mucus content of the both groups. The ulcer healing which occurred in the presence of a high gastric acid suggests that the effect of palm vitamin E on the healing of gastric lesions was not mediated via a reduction in gastric acid nor was it mediated through increasing prostaglandin E2 or mucus production. The most probable mechanism is via reducing lipid peroxidation as reflected by a significant decreased in gastric tissue MDA content.
In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation. The prevalent notion among sections of population in this country and perhaps in others is that "red pepper" popularly known as "Chilli," a common spice consumed in excessive amounts leads to "gastric ulcers" in view of its irritant and likely acid secreting nature. Persons with ulcers are advised either to limit or avoid its use. However, investigations carried out in recent years have revealed that chilli or its active principle "capsaicin" is not the cause for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits acid secretion, stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury causing agents. Epidemiologic surveys in Singapore have shown that gastric ulcers are three times more common in the "Chinese" than among Malaysians and Indians who are in the habit of consuming more chillis. Ulcers are common among people who are in the habit of taking NSAIDS and are infected with the organism "Helicobacter Pylori," responsible for excessive acid secretion and erosion of the mucosal layer. Eradication of the bacteria by antibiotic treatment and avoiding the NSAIDS eliminates ulcers and restores normal acid secretion.
Helicobacter pylori causes persistent infection in the gastric epithelium of more than half of the world's population, leading to the development of severe complications such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Several virulence factors, including cytotoxin-associated gene A (CagA), which is translocated into the gastric epithelium via the type 4 secretory system (T4SS), have been indicated to play a vital role in disease development. Although infection with strains harboring the East Asian type of CagA possessing the EPIYA-A, -B, and -D sequences has been found to potentiate cell proliferation and disease pathogenicity, the exact mechanism of CagA involvement in disease severity still remains to be elucidated. Therefore, we discuss the possible role of CagA in gastric pathogenicity.
The effect of treatment with Radix on ethanol-induced gastric lesions was investigated. The main ingredient of Radix is Eurycoma longifolia. Twenty-four rats of the Sprague-Dawley species were randomly divided into four groups. Three groups were given 0.5 mL 100% ethanol orally. Another group was used as a control and was given only distilled water orally (control). After 6 h all the rats were fed with normal diet. One group that was administered with ethanol was only given distilled water orally (no treatment). Another two groups that were administered with ethanol were treated with oral Radix 0.128 mg g(-1) b.wt. (Radix) and oral ranitidine 21.4 mg kg(-1) b.wt. (Ranitidine), respectively. After one week, all the rats were fasted overnight and sacrificed. The stomach was isolated and examined for the presence and severity of gastric lesions. Measurements for malondialdehyde content and gastric acid concentration were also done. It is found that the ulcer index was lower in the Radix and ranitidine group compared to the no treatment group whereas in the control group there was no lesion. There was no difference in ulcer index between the Radix and ranitidine group. The gastric MDA content was significantly higher in all the groups that were induced with ethanol compared to the control group but no difference between all the ethanol-induced groups. There was no difference in the gastric acid concentration in all groups. Hence it is concluded that Eurycoma longifolia in Radix is as effective as ranitidine in the treatment of ethanol-induced gastric lesions in rats.
CONTEXT: Bauhinia purpurea L. (Fabaceae) is a native plant species of many Asian countries, including Malaysia and India. In India, the root, stem, bark, and leaf of B. purpurea are used to treat various ailments, including ulcers and stomach cancer.
OBJECTIVE: In an attempt to establish its pharmacological potential, we studied the antiulcer activity of lipid-soluble extract of B. purpurea obtained via extraction of air-dried leaves using chloroform.
MATERIALS AND METHODS: The rats were administered the chloroform extract (dose range of 100-1000 mg/kg) orally after 24 h fasting. They were subjected to the absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation assays after 30 min. The acute toxicity study was conducted using a single oral dose of 5000 mg/kg extract and the rats were observed for the period of 14 days. omeprazole (30 mg/kg) was used as the standard control.
RESULTS: At 5000 mg/kg, the extract produced no sign of toxicity in rats. The extract exhibited significant (p < 0.05) dose-dependent antiulcer activity for the ethanol-induced model. The extract also significantly (p < 0.05) increased the gastric wall mucus production and pH of gastric content, while significantly (p < 0.05) reducing the total volume and total acidity of the gastric content in the pylorus ligation assay.
DISCUSSION AND CONCLUSION: The extract possesses antiulcer, antisecretory and cytoprotective activities, which could be attributed to its flavonoid and tannin content. These findings provide new information regarding the potential of lipid-soluble compounds of B. purpurea for the prevention and treatment of gastric ulcers.