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Trio-clar Versus Portulaca Oleracea and/or Foeniculum Vulgare Extracts on Induced Gastric Ulcer in Adult Female Albino Rats. A Histological Study
... These findings resembled those of Youssef, [22] who stated that diclofenac inhibits proliferation of gastric stem cells. Abd-Elhamid et al. [58] and Ali et al. [59] explained that NSAIDs inhibit cell proliferation and tissue regeneration by reducing the binding capacity of epidermal growth factor (EGF), a protein required for gastric cell proliferation and differentiation, to its receptors with subsequent inhibition of its signaling pathways. ...
... Recently, many studies have reported the uses of dendrimers as an oral drug delivery system due to their ability to transfer through the epithelial layer of the stomach [89,90]. In order to determine their suitability for oral delivery, we studied the effect of all dendrimers in the gastrointestinal tract compared to aspirin, since anti-inflammatory drugs are the most common cause of gastric ulcers [91]. Microscopic examination of a stomach tissue section from aspirin group ( Figure 14) revealed serious histopathological alterations, and extensive mucosal damage was noticed with substantial tissue loss. ...
Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.
... Recently, many studies have reported the uses of dendrimers as an oral drug delivery system due to their ability to transfer through the epithelial layer of the stomach [89,90]. In order to determine their suitability for oral delivery, we studied the effect of all dendrimers in the gastrointestinal tract compared to aspirin, since anti-inflammatory drugs are the most common cause of gastric ulcers [91]. Microscopic examination of a stomach tissue section from aspirin group ( Figure 14) revealed serious histopathological alterations, and extensive mucosal damage was noticed with substantial tissue loss. ...
Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.
Gastric ulcer, affecting 10% of the global population, can lead to severe complications as perforation, bleeding, and fatal outcomes. Valerian extract and coenzyme Q10 show a potential as therapeutic agents that decrease inflammation and protect against oxidative damage. To evaluate the therapeutic effect of the co-administration of valerian extract and coenzyme Q10 versus the administration of each of them alone in ameliorating experimentally induced gastric ulcer. Rats were randomly assigned into the following groups: the control, the ulcer-induced, the treated groups: valerian extract, coenzyme Q10, and both treatments, all administered orally one hour after orally ingestion of ethanol, and finally untreated group. After the rats were sacrificed, their stomachs were analyzed macroscopically, histologically, and immunohistochemically. The ulcer-induced group demonstrated severe gastric damage with hyperemia and brownish hemorrhagic spots macroscopically, along with various histological changes, including deep gastric ulcers and multiple erosions. There was complete destruction of the fundic glands and their lining cells, areas of hemorrhage, loss of mucopolysaccharide content, and fibrosis which were confirmed by morphometrical studies. Scanning electron microscopy revealed wide ulcers and complete shedding of surface mucous epithelial cells. Valerian extract and coenzyme Q10 groups showed partial improvement with an increased rate of proliferation detected by immunohistochemical study. The combination of both drugs provided restoration of the gastric mucosa to a nearly control-like appearance. Combined treatment with valerian and Coenzyme Q10 was more effective than either alone in restoring the mucous barrier, regenerating epithelial cells, and reducing inflammation.
Background
levothyroxine sodium is considered the top drug for treatment of people with hypothyroidism. It is manufactured from the original biological hormone thyroxine. This replacement treatment is almost the only solution for hypothyroid patients. The mucosal lining of the stomach is one of the defense mechanisms protecting the body from harmful effects of ingested exogenous substances and microorganisms. The gastric mucosa is vulnerable to toxic substances.
Aim of the Work
In this work we tried to investigate the histopathological effect of chronic oral levothyroxine sodium administration on the fundic mucosa of the adult male albino rats using a histological study.
Materials and Methods
Thirty adult male albino rats weighing 150-200 grams were used, divided into three main groups: Group I (control group): included 10 rats that received no treatment for the same periods as the experimental animals. Group II: It Included 10 rats that each rat received levothyroxine sodium dissolved in distilled water and given for each rat orally by orogastric tube in a dose equal to 2mcg/kg per day for 60 days. Group III This group consisted of 10 rats, each rat received levothyroxine sodium by orogastric tube in a dose equal to 4mcg/kg per day for 60 days. The fundic gastric mucosa specimens were subjected to histological (light, immunostaining and scanning electron microscopic examination). The data were analyzed statistically.
Results
The current study of the control group revealed the normal architecture of gastric wall of rats at the fundus formed of the mucosa, submucosa, muscularis mucosa the gastric glands, and muscularis externa. Group II showed widening of the gastric pits and their lining epithelium became thinner, increased mucous secretion filling the dilated pits. Group III showed more obvious widening of the gastric pits and more mucous secretion lodging the pits orifices with sloughing of the surface epithelium.
Conclusion
Finally, we can conclude that the long-term administration of oral levothyroxine sodium can produce structural harmful changes in the gastric mucosa of adult male rats.
The first five review articles in this series presented anticancer, anti-inflammatory, antidiabetic, antimicrobial and antiviral, and antioxidant activities of the most important wild edible plants of eastern Mediterranean region, which we named as the “Deca-plants” (D-P). In this article other activities will be presented. Although the activities and properties that will be introduced in this article are very important, none of them was published in a large number of research articles that is close to each one of the activities presented in the first five articles. In rare cases that they were overlooked, some of the properties discussed in the first five articles will be presented here. So, this will be the last article of this series and will include many figures of structures of active secondary metabolites contained in the plants. We tried avoiding using publications that we cited in the first five articles unless they report activities that were not discussed in the first five parts. The last sections of this article will discuss the presented activities, present selected similar activities of Non-Deca-Plants, when the criteria of selection are wild and edible; and conclusions will be drawn with future research and applications.
Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential of Althaea officinalis and Solanum nigrum extracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receiving Althaea officinalis and Solanum nigrum. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat’s stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol, Althaea officinalis, and Solanum nigrum pretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.
Background: Phytoesrogenis plant derived compounds which have an estrogenic effect.
Objectives: The present study was carried out to investigate some pharmacological and biochemical effects of fennel oil on male albino rats.
Materials and methods: Twelve animals were divided randomly into two groups. Group A: Control.
Group B: Treated rats. The rats were given an oral dose of 1 ml/kg body weight/day fennel oil once daily for one month. At the end of the experiment, blood samples were collected for biochemical analysis.
Results: The fennel oil induced highly significant decrease (p<0.01) in total cholesterol(TC), triglycerides (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), LDL/high-density lipoprotein (HDL), while significant increased (p<0.05) HDL. In addition, it showed highly significant decrease (p<0.02) in FSH, testosterone and sperm count compared to normal control group.
Conclusion: Fennel herb has several therapeutic benefits, but it also has negative effect on male sex hormone and sperm count. So men must reduce their usage of it.
Quercetin (QUE) is a flavonoid found in several plants and
commonly distributed in edible vegetables and fruits. To evaluate the
effect of co-lyophilization of naproxen (NPX) with QUE at different
weight ratios on physicochemical characteristics induced gastric
irritation, and drug pharmacokinetics. NPX binary systems with QUE in
different weight ratios were prepared by freeze-drying alkalinized
solutions, and were characterized in terms of physicochemical properties
as well as NPX dissolution rate in acidic pH. NPX-induced gastric
inflammation studies were carried out in rats for 7 days. The
pharmacokinetics of the two formulations were assessed to evaluate the
bioavailability of NPX-QUE 1:2 co-lyophilizate. Westar rats were
administered oral doses equivalent to 40 mg kg-1 of NPX and blood samples
were taken from the retro-orbital vein of rats at 0.5, 1.0, 1.5, 2.0,
3.0, 4.0, 6.0, 8.0 12.0, and 24.0 h post dosing. Co-lyophilization of NPX
with QUE enhanced drug dissolution rate in the acidic medium, which was
correlated with an increased QUE weight ratio in the co-lyophilizates.
Rat stomachs from group V (NPX-QUE 1:2 co-lyophilizate) showed nonsignificant changes, and biopsies from this group showed no significant
leukocyte infiltration and edema in the mucosa. The bioavailability of
NPX-QUE 1: 2 co-lyophilizate was similar to the control sample. NPX-QUE
1: 2 co-lyophilizate could be an alternative to NPX in the treatment of
arthritis as it minimizes the potential for gastric irritation and
enhances safety while retaining the same efficacy and bioavailability.
Heat shock proteins 70 and 90 (HSP-70 and HSP-90) are associated with gastroprotective and ulcer healing potentials. Reports in literatures have shown that age affects gastric ulcer healing, but the role of these heat shock proteins in relation to age has not been fully understood. This study, therefore, investigated changes in the expression of HSP-70 and HSP-90 in the gastric mucosa of 3, 6 and 18-month old rats during healing of Acetic acid-induced gastric ulcers. Male Wister rats (aged 3, 6 and 18 months) were divided into 3 groups according to their ages. Acetic acid ulcer model was used for this study. Ulcer area, oxidative stress, antioxidant markers, HSP-70 and HSP-90 concentration by ELISA and expression by immunohistochemistry was assessed. Results obtained indicate the highest percentage area healed on day 14 in 3 months old rats (100%), while percentage healing for 6 and 18 months old rats was 89.00% and 55.29%, respectively. Malondialdehyde (MDA) concentration was directly proportional to age, while antioxidant enzyme (Superoxide dismutase (SOD) and catalase (CAT)) activities were inversely proportional to age. The concentration and expression of HSP-70 were inversely proportional to age while HSP-90 had directly proportionality to age. The histological architecture also confirmed the faster rate of healing in 3-month old rats recorded in this study.This study indicates that HSP-70 and HSP-90 play different roles in age-related healing of gastric ulcers.
As a result of accumulated experience from the past generations, today, all the world's cultures have an extensive knowledge of herbal medicine. Plants are a valuable source of a wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances, colours, biopesticides and food additives. This study was designed to highlight the chemical constituents and pharmacological effects of Foeniculum vulgare.
ABASTRACT
Introduction: Ellagic acid (EA) is one of the naturally occurring polyphenols of plant origin. The EA has been known as a gastroprotective agent of natural plant origin. Aim of the work: The current study was designed to evaluate the effect of EA on the gastric mucosal injury induced by aspirin in adult male albino rats. Materials and Methods: 48 adult male albino rats were divided into 4 equal groups: group I; control group, group II; E.A. group: in this group the animals received daily oral dose of E.A. (50mg/kg). Group III; aspirin group: in which the animals received (O.2gm/kg) of aspirin as a daily oral dose. Group IV; E.A. & aspirin group: in this group the animals were given both E.A. & aspirin. The experiment was continued for 3 weeks, after which, the stomach samples were collected, processed for histological & immunohistochemical study. The mean number of proliferating cell nuclear antigen (PCNA) positive cells were measured and statistically represented. In addition, gastric Ph, gastric wall mucus content, peptic activity, angiogenic marker, as: Vascular endothelial growth factor (VEGF), oxidative stress markers, and inflammatory marker were also estimated and statistically represented. Results: Examination of sections of aspirin group revealed that aspirin induced desquamation of gastric epithelium, which may extend to reach the base of some gastric glands. Mucus contents and angiogenic marker were decreased, while the peptic activity, gastric acidity (gastric ph), oxidative stress, and inflammatory makers were increased. The PCNA positive cells were significantly decreased in this group if compared with the control group. The combined use of EA & aspirin showed generalized improvement of most histological changes and the other parameters, if compared to the control. Conclusion: E.A. administration protects the gastric mucosa from damage induced by aspirin.
KEYWORDS: Aspirin, Gastric Mucosa, Ellagic Acid, Proliferating Cell Nuclear Antigen.
Introduction: Medicinal plants with phenolic compounds have been shown to have antimicrobial and antioxidant activities. The objective of the study was to evaluate the anti-ulcer effects of ethanolic extracts of Plumbaginales namely P. auriculata, P. indica and P. zeylanica and plumbagin in aspirin and ethanol induced gastric ulcer models. Methods: In vivo studies including DPPH scavenging assay, lipid peroxidase inhibition assay, acid neutralizing capacity test, aspirin- and ethanol-induced ulcer models were performed to assess the antioxidant and antiulcer effects of plants. By using the models of Aspirin (200 mg/kg, 1 hour after the administration of last dose of the extract/ranitidine) and ethanol (1 mL/200 g, 90%) induced ulcer, animals were randomly divided into three groups of six animals each. Group I served as positive control, group II acted as standard and received ranitidine (20 mg/kg). The group III was treated with ethanolic extract by oral route in a dose of 300 mg/kg for a period of 5 days. The animals were sacrificed and the stomach was then excised and cut along the greater curvature, washed carefully with 5.0 mL of 0.9% NaCl and ulcers were scored. Results: Both the aspirin- and ethanol-induced models of ulcer with various extracts of Plumbaginales showed significant acid neutralizing and antioxidant properties. Conclusion: This study suggests that root extracts of P. auriculata may have good quality potentials for use in peptic ulcer diseases and that P. auriculata possesses an antiulcer effect.
ABSTRACT
Aiming to evaluate the protective effect of garlic on aspirin induced peptic ulcer in comparison with misoprostol and omeprazole drugs and its possible mechanisms. Forty white male albino rats were used. Total acid content, ulcer area/mm2, histological study, mucosal & serum Total Antioxidant Capacity (TAC) by calorimetry and mucosal & serum PGE2 and serum TNF-α by ELISA were assayed. Titrable acidity and total acid output decreased in garlic, misoprostol and omeprazole treated groups. Garlic, misoprostol and omeprazole improved gastric mucosa and decreased ulcer formation and ulcer area/mm2. Aspirin decreased PGE2 in gastric mucosa and serum. Co-administration of garlic to aspirin significantly increased PGE2 near to normal in gastric mucosa. Aspirin significantly increased serum TNF-α than control and other groups. Garlic is suggested to protect the stomach against ulcer formation induced by aspirin by reducing gastric acidity, ulcer area, improve gastric mucosa, increasing PGE2 and decreasing TNF-α.
Keywords: Aspirin, Garlic, Misoprostol, Omeprazole, Peptic ulcer
Background: Peptic ulcer is mucosal lesion of the stomach or duodenum in which acid and pepsin play major pathogenic role. The major forms of peptic ulcer are gastric ulcer and duodenal ulcer, often caused by Helicobacter pylori, non-steroidal anti-inflammatory drugs (NSAIDs), physiological stress and smoking. The objective of this was to assess the prevalence of different types of peptic ulcer and treatment modalities in peptic ulcer patients. Methods: A total of 425 patients of different age groups were selected from different areas of Hyderabad city having peptic ulcer. There were 166 (39%) male and 259 (61%) females. Data were collected on a questionnaire. Subjects were divided into 5 age groups. Results: Peptic ulcer was more prevalent in age group 20–30 years and mostly found in females (60%) compared to males (40%). Gastric ulcer was seen mostly (68%) compared to duodenal ulcer (32%). The tendency of treatment type came out to be allopathic 38%, homeopathic 4%, and herbal 4%. The tendency of combination therapy was allopathic+homeopathic 34%, homeopathic+herbal 4%, allopathic+herbal 12%, and allopathic+homeopathic+herbal 4%. Conclusion: Gastric ulcer is more common than duodenal ulcer in Hyderabad that is in contrast to reported data. The patients suffering from either types of ulcer preferred allopathic treatment followed by homoeopathy and herbal medication.
Introduction:
Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy.
Methods:
Rats were treated twice daily with pantoprazole sodium (PTZ; 10 mg/kg peroral) or vehicle for a total of 10 days. In some experiments, Diclofenac sodium (DCF; 9 mg/kg) or vehicle was administered orally twice daily for the final 5 days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12 hours after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated.
Results:
The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ.
Conclusions:
This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit, serum albumin, serum total protein levels and IP alteration, known to occur in patients receiving NSAIDs. Additionally, this paper provides yet another evidence for PPI induced exacerbation of NSAID enteropathy.
Keywords: NSAIDs; Gastroenteropathy; Methods; PPIs; Rats; Enteropathy; Haemorrhagic lesions
Common purslane (Portulaca oleracea L.) is an annual weed rich in omega-3 fatty acids which is consumed for its edible leaves and stems. In the present study six different genotypes of common purslane (A-F) were evaluated for their nutritional value and chemical composition. Nutritional value and chemical composition depended on genotype. Oxalic acid content was the lowest for genotype D, whereas genotypes E and F are more promising for commercial cultivation, since they have low oxalic acid content. Genotype E had a very good antioxidant profile and a balanced composition of omega-3 and omega-6 fatty acids. Regarding yield, genotype A had the highest yield comparing to the other genotypes, whereas commercial varieties (E and F) did not differ from genotypes B and C. This study provides new information regarding common purslane bioactive compounds as affected by genotype and could be further implemented in food industry for products of high quality and increased added value.
A near infrared spectroscopic method for the simultaneous determination of the active principles clarithromycin, tinidazole and omeprazole in a pharmaceutical preparation was developed. The three active principles are quantified using partial least-squares regression methods. The proposed method is applicable over a wide analyte concentration range (80–120%) of labeled content, so it requires careful selection of the calibration set and to ensure thorough homogenization of the product. The method was validated in accordance with the ICH standard validation guidelines for NIR spectroscopy by determining its selectivity, linearity, accuracy, precision and stability. Based on the results, it is an effective alternative to the existing choice (HPLC) for the same purpose.
There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for liver. In this review, we have introduced some medicinal plants that are used mainly for the treatment of liver disorders in Iranian folk medicine, with focus on their hepatoprotective effects particularly against CC14 agent. In this study, online databases including Web of Science, PubMed, Scopus, and Science Direct were searched for papers published from January 1970 to December 2013. Search terms consisted of medicinal plants, traditional medicine, folk medicine, hepatoprotective, Iran, liver, therapeutic uses, compounds, antioxidant, CC14, anti-inflammatory, and antihepatotoxic, hepatitis, alone or in combination. Allium hirtifolium Boiss., Apium graveolens L., Cynara scolymus, Berberis vulgaris L., Calendula officinalis, Nigella sativa L., Taraxacum officinale, Tragopogon porrifolius, Prangos ferulacea L., Allium sativum, Marrubium vulgare, Ammi majus L., Citrullus lanatus Thunb, Agrimonia eupatoria L. and Prunus armeniaca L. are some of the medicinal plants that have been used for the treatment of liver disorders in Iranian folk medicine. Out of several leads obtained from plants containing potential hepatoprotective agents, silymarin, β-sitosterol, betalain, neoandrographolide, phyllanthin, andrographolide, curcumin, picroside, hypophyllanthin, kutkoside, and glycyrrhizin have been demonstrated to have potent hepatoprotective properties. Despite encouraging data on possibility of new discoveries in the near future, the evidence on treating viral hepatitis or other chronic liver diseases by herbal medications is not adequate.
Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination), and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (~80% inhibition of COX-2) while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin production in the vascular wall and other organs. Each patient’s clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs. New methods are emerging to assist clinicians in the selection of appropriate NSAIDs and their doses/schedules, such as biomarkers that may predict the response to NSAID treatment in individual patients.
Gastric ulcer is one of the most prevalent gastrointestinal disorders and still remains a major on-going health concern. Phosphodiesterase V inhibitors (PDE V) are drugs currently used in the treatment of patients with erectile dysfunction and pulmonary hypertension. They act by increasing blood flow to tissues in response to increased cGMP levels. They are also Nitric Oxide (NO) donors. NO is a potent vasodilator which increases blood flow in tissues where present thus preventing tissue damage. This study therefore examined the effects Tadalafil (TAD) on Indomethacin-induced gastric ulceration in rats. Three studies were directed at examining the effects of Tadalafil on gastric ulceration, ulcer dimensions and histological profile in indomethacin-induced rats. Male Wistar Albino rats weighing between 180-220 g were used. Each experimental group containing 6 rats were divided based on the following pre-treatments: Group I (Control)-saline (8 mL kg -1), Group II-IV were pre-treated with graded doses of Tadalafil (2, 5 and 10 mg kg -1 body weight, respectively), Group V (Reference)-Cimetidine 100 mg kg -1. Ulcer was induced by administration of indomethacin (40 mg kg -1 p.o) 30 min following pre-treatments. Results showed that Tadalafil significantly reduced Indomethacin-induced gastric ulcers when compared with the control group (p<0.05) at high doses. The ulcer area, depth and width were significantly different between the control group and the Tadalafil 10 mg kg -1 BW group. Tadalafil had ulcer-reducing effects similar to that of the reference drug, cimetidine. Similar pattern of dose-dependent attenuation of ulcer severity was observed in the histological study. This study provides evidence that Tadalafil possesses significant anti-gastric ulcer effects as it dose-dependently reduced gastric ulcers induced by Indomethacin in rats.
The gastric mucosa plays an important role in the physiological function of the stomach. This mucosa acts as gastric barrier, which protects deeper located cells against the detrimental action of the gastric secretory components, such as acid and pepsin. Integrity of the gastric mucosa depends upon a variety of factors, such as maintenance of microcirculation, mucus-alkaline secretion and activity of the antioxidizing factors. The pathogenesis of gastric mucosal damage includes reactive oxygen species (ROS), because of their high chemical reactivity, due to the presence of uncoupled electron within their molecules. Therefore they cause tissue damage, mainly due to enhanced lipid peroxidation. Lipid peroxides are metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The local increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage. Superoxide dismutase (SOD) is the main enzyme, which neutralizes ROS into less noxious hydrogen peroxide. A decrease of SOD activity is an indicator of impairment of the protective mechanisms and significantly contributes to cell damage. Hydrogen peroxide is further metabolized to water in the presence of reduced glutathione (GSH). GSH can also work synergetically with SOD to neutralize ROS. The reactions between GSH and ROS yields glutathione free radical (GS(•)), which further reacts with GSH leading to free radical of glutathione disulphide (GSSG(•)). This free radical of GSSG can then donate an electron to the oxygen molecule, producing O2 (•-) Subsequently, O2 (•-) is eliminated by SOD. Adecrease of the GSH level has detrimental consequences for antioxidative defense cellular properties. Gastric mucosa, exposed to stress conditions, exhibits an enhancement of lipid peroxidation (increase of MDA and 4-HNE), as well as a decrease of SOD activity and GSH concentration. This chain reaction of ROS formation triggered by stress, appears to be an essential mechanism for understanding the pathogenesis of stress - induced functional disturbances in the gastric mucosa leading to ulcerogenesis.
Background and Objectives: Decrease in serum lipids by dietary or pharmacological intervention prevents progression of atherosclerosis and cardiovascular diseases. The aim of this study was to investigate the effects of hydro-alcoholic extract of celery (Apium graveolens) on lipid profile of rats fed a high fat diet. Materials and Methods: In this experimental study, 24 Wistar rats were randomly allocated into four groups. The control group received saline with high-fat diet and treatment groups did hydroalcoholic extract at doses of 100 and 200 mg/kg/BW with high fat diet by gavage over a 30-day period. Afterwards, the serum levels of lipids (triglyceride, cholesterol, LDL, HDL, and VLDL) were determined. The data were analyzed by one-way ANOVA test using SPSS15 software. Results: Hydro-alcoholic extract of celery significantly decreased cholesterol and LDL in treatment groups compared with control group (P≤0.05); but had no significant effects in serum levels of triglyceride, HDL, and VLDL (P>0.05). Conclusions: Probably celery consumption due to the antioxidant properties leads to appropriate changes in serum lipid profiles and reduces them. Therefore it could be useful in the treatment of hyperlipidemia.
Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy.
To investigate the role of the hydrogen-rich water (HRW) in the prevention of aspirin-induced gastric mucosal injury in rats.
Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), interleukin (IL)-06 and tumor necrosis factor (TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2 (COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively.
Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores (4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group (2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues (37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues (46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum (505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues (staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05).
HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.
This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats.
Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively.
Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity.
Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status.
Background:
Musculoskeletal disorders are a growing burden on the health care system in the United States. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to assist in the management of mild-to moderate musculoskeletal pain. After the withdrawal of rofecoxib because of cardiovascular toxicity, the safety of these agents became a topic of controversy and confusion. Recent evidence is facilitating a better understanding of the risks and mechanisms by which NSAIDs cause injury. In an effort to raise awareness, this review addresses the current challenges, recent progress, and novel strategies for improving tolerability. With new data to help guide decision making and the anticipated increase in pharmacological options for managing musculoskeletal pain, the role of the managed care professional is particularly important in this evolving field.
Objectives:
To review recommendations for the appropriate use of NSAIDs, incorporate risk/benefit analysis into decision making, and evaluate the efficacy and safety of recently approved and emerging NSAID formulations.
Summary:
Musculoskeletal-related conditions are a major public health burden. NSAIDs are among the most commonly used medications for musculoskeletal conditions. Since the introduction of selective cyclooxygenease-2 (COX-2) inhibitors (or coxibs), there has been ongoing discussion and debate about the safety of all NSAIDs. Current available evidence suggests both traditional NSAIDs and coxibs increase the risk of gastrointestinal and cardiovascular toxicity; however, with proper risk assessment, these dangers can be limited. Moreover, new and emerging NSAID formulations and delivery systems aim to enhance the effectiveness and reduce the toxicity associated with these anti-inflammatory agents.
Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates, as stopping aspirin therapy is associated with higher mortality rates. It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding, and every effort should be exercised to prevent the bleeding complications.
Portulaca oleracea L. is a traditional edible and medicinal plant in China. Flavonoids are one of the main active ingredients of this plant.
Five extraction technologies of flavonoids from P. oleracea L. were investigated and compared, including microwave-assisted extraction, ultrasonic extraction, reflux extraction, Soxhlet
extraction, and marinated extraction. The results showed that microwave-assisted extraction was most suitable for the extraction
of flavonoids from P. oleracea L. because of its high effect and short extraction time. The found optimum extraction conditions were that the ethanol concentration
was 70% (v/v), solid–liquid ratio was 1:50, extracting temperature was 50°C and irradiation time was 9min. Quantification was performed
by means of UV–Vis spectrophotometry with chromogenic system of NaNO2–Al (NO3)3–NaOH. Under the optimum conditions, the calibration curve for the analyte was linear with the correlation coefficients greater
than 0.9999. The average recovery was 102.6%, and its RSD was 1.13%(n = 5). Eight types of P. oleracea L. according to different habits were investigated. The total content of flavonoids was 7.16, 7.10, 9.38, 6.82, 6.78, 11.36,
5.12, and 1.76mg g−1, respectively.
KeywordsFood Analysis-
Portulaca oleracea L.-Flavonoids-Microwave-Assisted Extraction-UV–Vis Spectrophotometry
Foeniculum vulgare (Apiaceae) commonly known as fennel is a well known and impor-tant medicinal and aromatic plant widely used as carminative, digestive, lactogogue and diuretic and in treating respiratory and gastrointestinal disorders. Its seeds are used as flavourings in baked goods, meat and fish dishes, ice cream, alcoholic beverages and herb mixtures. Phenols, phenolic glycosides and volatile aroma compounds such as trans-anethole, estragole and fenchone have been reported as the major phytoconstituents of this species. Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the ability of F. vulgare to exhibit antifungal, antibacterial, antioxidant, antithrombotic and hepatoprotective activities, lend-ing support to the rationale behind several of its therapeutic uses. Phenolic compounds isolated from F. vulgare are considered to be responsible for its antioxidant activity while the volatile aroma compounds make it an excellent flavouring agent. The present review is an up-to-date and compre-hensive analysis of the chemistry, pharmacology, traditional uses and safety of F. vulgare.
The protective and therapeutic effects of Argyreia speciosa Sweet (Convolvulaceae) against ethanol-induced gastric ulcer in rats were evaluated. Ethanolic and water extracts of the aerial plant parts (200 mg/kg body weight) were orally administered daily for seven days prior to or after ulceration with one oral dose of 1 mL absolute ethanol on 24-h empty stomachs. Rats were divided into eleven groups. Group 1 served as control. To groups 2 and 3 each extract was administered. Groups 4 to 6 received each extract or ranitidine (100 mg/kg body weight) prior to ulcer induction. Groups 7 to 9 received each extract or ranitidine post ulcer induction. Groups 10 and 11 were gastric ulcerative rats after one hour and one week of ethanol induction. The evaluation was done through measuring ulcer indices: stomach acidity and volume, lesion counts, mucus, and prostaglandin E2 contents. Oxidative stress marker, i. e. malondialdehyde, glutathione, and superoxide dismutase, were estimated. Certain marker enzymes for different cell organelles, i. e. succinate and lactate dehydrogenases, glucose-6-phosphatase, acid phosphatase, and 5'-nucleotidase, were evaluated. The work was extended to determine the collagen content and the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index, antioxidant levels, collagen content, and the marker enzymes. The water extract attenuated these increments and was more potent as a protective agent, while the ethanol extract exhibited stronger therapeutic potency. In conclusion, A. speciosa acted as antiulcer agent. More detailed studies are required to identify the compounds responsible for the pharmacological effect.
Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.
Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.
Phytoestrogens are non-steroidal secondary metabolites with similarities in structure and biological activities with human estrogens divided into various classes of compounds, including lignans, isoflavones, ellagitannins, coumestans and stilbenes. Similarly, phytosteroids are steroidal compounds of plant origin which have estrogenic effects and can act as agonists, antagonists, or have a mixed agonistic/antagonistic activity to animal steroid receptors. On the other hand, saponins are widely distributed plant glucosides divided into triterpenoid and steroidal saponins that contribute to plant defense mechanism against herbivores. They present a great variation from a structural point of view, including compounds from different classes. In this chapter, the main vegetable sources of these compounds will be presented, while details regarding their biosynthesis and plant functions will be also discussed. Moreover, considering the significant bioactive properties that these compounds exhibit, special focus will be given on their health effects, either beneficial or adverse. The practical applications of these compounds in agriculture and phytomedicine will be also demonstrated, as well as the future prospects for related research.
Portulaca oleracea is a fleshy annual herb which is distributed throughout the temperate and tropical areas of the world. This plant is used in traditional medicine as a gastric sedative. Air-dried specimen of Portulaca oleracea was cold-extracted in distilled water and 70% methanol respectively for 72 hours and concentrated using steam bath. The resulting aqueous and methanol extracts (AEPO and MEPO) were then subjected to gastric acid secretory study in male rats. Fifty -five male rats (150-200 g) were randomly divided into AEPO (25, 50, 75 mg/kg), MEPO (25, 50, 70 mg/kg) and histamine (1 mg/kg) treated groups. The combination of extracts with histamine (1 mg/kg) and cimetidine (100 mg/kg) groups were used to investigate the probable mechanism of action. The experimental animals also served as the control. Gastric acid secretory response was determined by titration method. Data were analyzed using t-test at p<0.05. The results showed that treatment of rats with all the doses of AEPO and MEPO caused significant (p<0.05) reductions in gastric acid secretion. The submaximal doses of AEPO (50 mg/kg) and MEPO (50 mg/kg) significantly (p<0.05) inhibited histamine-induced gastric acid secretion. Cimetidine seemed to potentiate or augment the extracts (AEPO and MEPO) inhibition of gastric acid secretions. The results suggest that the extracts (AEPO and MEPO) gastric acid anti-secretory effects could be mediated via H2-receptors.
Objective:
Garlic, in its natural plant state, has a great history in ancient medicine as a remedy for many diseases. In our study, the gastroprotective effect of aged garlic extract (AGE) and the possible underlying mechanisms were investigated in an experimental model of indomethacin-induced gastric ulcer.
Methods:
Male Wistar rats were divided into four groups: (normal control, n = 20), ulcer control (indomethacin group, n = 20), (omeprazole group, n = 30) and (garlic group, n = 20). Each dose of garlic and omeprazole was given to rats orally daily for 10 consecutive days before induction of ulcer by indomethacin. Indomethacin was given as a single oral dose (100 mg/kg). Four hours later after indomethacin treatment, the rats were sacrificed and gastric tissue was obtained for histopathological examination, calculation of ulcer index and measurement of oxidative stress markers as well as gastroprotective mediators.
Results:
The results showed that indomethacin induced gastric ulcer (ulcer index = 2900), was associated with a significant increase of tumor necrosis factor-alpha and malondialdehyde, and significant decrease of the gastroprotective mediators prostaglandin E2, glutathione (GSH) and nitric oxide (NO) compared with normal control. Pretreatment with AGE produced comparable results with those obtained in the omeprazole group; the preventive index in the AGE group was 83.4% compared with 94.5% in the omeprazole group. The prophylactic role of AGE in indomethacin-induced ulcer was, in part, mediated by decreasing oxidative stress and increasing gastric level of PGE2, GSH, and NO.
Conclusion:
AGE corrected the histopathological abnormalities in gastric tissue and proved a promising gastroprotective role in gastric ulcer.
Objective: This study was designed to evaluate the reproductive effect of isolated ergosterol constituent of Portulaca oleracea on reproductive parameters in male albino rats. Methods: The isolated compound was administered on daily basis for 25 days at doses of 0.50 mg/kg and 0.75 mg/kg and blood samples were collected for hormonal assay, semen analysis was also carried out. Data were analysed using ANOVA at p<0.05. Result: Treatment of rats with 0.50 mg/kg BW and 0.75 mg/kg BW caused decrease in testosterone levels, sperm motility and sperm count as well as increase in the percentage of abnormal sperm cells relative to their respective controls. Conclusion: These findings on the reproductive parameters suggests that isolated ergosterol constituent of Portulaca oleracea has deleterious effect on reproductive functions in male albino rats.
Introduction: the gastric mucosa is susceptible to the effects of aggressive factors, which are counterbalanced by mucosal defensive factors. Acid peptic diseases result from the imbalance between these aggressive and defensive factors. Aspirin-induced ulcer is a model of NSAIDs-induced damage in which neutrophil infiltration plays a key role. Objective: this paper investigates the protective effect of D-002 against aspirin- -induced ulcers and associated neutrophil infiltration in the gastric mucosa. Methods: rats were randomized into six groups of 8 rats each. A negative vehicle control, and five aspirin (300 mg/kg)-treated groups: a positive control, orally treated with the vehicle, three with D-002 (25, 50 and 100 mg/kg, respectively) and other with 10 mg/kg Omeprazole. Five hours after induced damage the rats were sacrificed. The stomachs were removed and opened, and lesions examined macroscopically and microscopically. Ulcer indexes and neutrophil infiltration per ulcer areas were measured. Results: all positive, none negative, controls exhibited aspirin-induced ulcers. Oral treatment with D-002 (25-100 mg/kg) dose-dependently and significantly reduced aspirin-induced gastric lesions (37 to 75 %), the mean number of microscopic ulcers (40 to 72 %) and neutrophil infiltration (41.7 to 83.1 %) in the rat gastric mucosa. Conclusion: Oral treatment with D-002 (25-100 mg/kg) effectively protects against aspirin-induced ulcers and decreases the neutrophil infiltration in the gastric mucosa induced by aspirin ulceration.
Introduction α-Lipoic acid (ALA), an endogenous agent, has been shown to combat oxidative stress. Aim of the work The aim of the study was to evaluate the protective effect of ALA on fundic gastric mucosal damage induced by acetyl salicylic acid (ASA). Materials and methods Fifty adult male albino rats were divided into four groups: group I (the control group), group II that received ALA for 2 weeks (subgroup IIa) and for 4 weeks (subgroup IIb), group III that received ASA for 2 weeks (subgroup IIIa) and for 4 weeks (subgroup IIIb), and group IV that received ALA 30 min before ASA for 2 weeks (subgroup IVa) and for 4 weeks (subgroup IVb). At the end of the experiment, specimens from the fundus of the stomach were processed for light and electron microscopic examinations. The mean number of proliferating cell nuclear antigen (PCNA)-positive cells, parietal cells, and the mean thickness of the fundic mucosa were measured and the results were statistically analyzed. Results Examination of sections revealed that ASA for 2 weeks induced widening of the gastric pits and focal mononuclear cellular infiltration. The mucous content of the mucosa was apparently increased and PCNA-positive cells were significantly decreased compared with the control group. ASA for 4 weeks resulted in extensive desquamation, thinning out of the mucosa, and diffuse mononuclear cellular infiltration. The collagen content of the lamina propria showed an apparent increase, whereas the mucous content showed an apparent decrease. The parietal cell count and the PCNA-positive cells were significantly decreased compared with the control group. In ultrathin sections, parietal cells showed cytoplasmic vacuoles, decreased intracellular canaliculi, and mitochondria, whereas the chief cells showed dilated rough endoplasmic reticulum and decreased secretory granules. Concomitant use of ALA showed a histological profile nearly comparable with that of the control group in both subgroups IVa and IVb. Conclusion ALA administration prevented the structural changes of the gastric mucosa induced by ASA.
This study evaluated anti-gastric ulcer and anti-secretory effects of folkloric medicinal plant, Foeniculum vulgare L., (Family:Apiaceae) in rats. The gastric ulcer protective potential of an aqueous suspension of 'Fennel' Foeniculum vulgare (FVS) was evaluated against different acute gastric ulcer models in rats induced by pyloric ligation (Shay), hypothermic restraint stress, indomethacin and by necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl). Fennel suspension, 250 and 500 mg kg(-1) b.wt. administered orally (intraperitoneally in Shay rat model) showed a dose-dependent ulcer protective effects in all the above models. Besides, the FVS offered protection against ethanol-induced depletion of Gastric Wall Mucus (GWM); replenished the reduced nonprotein sulfhydryls (NP-SH) concentration and modulated malondialdehyde (MDA) contents in the gastric tissue. Ethanol induced histopathological lesions of the stomach wall characterized by mucosal hemorrhages and edema that was reversed by FVS. Pretreatment of rats with FVS provided significant protection of gastric mucosa through its antioxidant capacity and/or by attenuating the offensive and by enhancing the defensive factor.
This study was designed to evaluate the efficacy of the freeze-dried supplements of purslane in reducing blood lipids in hypercholesterolemic adults. Fresh purslane leaves were freeze-dried and the fatty acids content analyzed. Eleven (11) hypercholesterolemic subjects (5 females and 6 males) volunteered to participate in the study. The subjects consumed step I diet during a 2-week acclimation period and switched to step I diet supplemented with freeze-dried purslane leaves (6 g/day) for 4 weeks. Subjects were instructed to incorporate the freeze-dried supplements into their meals at lunch (3 g) and dinner (3 g) during the 4 weeks experimental period. Fasting blood samples were collected at the end of the acclimation period and at 2-weeks interval during the experimental period for analysis of plasma cholesterol, LDL-cholesterol, HDL-cholesterol and triacylglycerol concentrations. Data were subject to analysis of variance and means separation was conducted using the Duncan multiple range test (DMRT). Consumption of purslane for 4 weeks reduced (P < 0.05) plasma total cholesterol and LDL-cholesterol. HDL-cholesterol levels were increased (P < 0.05). Plasma triacylglycerol concentrations were not affected by the consumption of purslane supplements. Results suggest that purslane supplements have the potential to alter blood lipid metabolism in hypercholesterolemic subjects and can lower the risk of heart disease. In addition, nutrient analysis confirmed that purslane is a rich source of polyunsaturated fatty acids, crude protein, vitamins and minerals.
Portulaca oleracea referred to the common purslane considered one of the important unknown plants in
Egypt. This study was carried out to investigate the biological, histopathological and anticancer effect of previous
plant. Chemical composition (total acidity, protein, crude fiber, ash content, minerals, phenolic and flavonoids
compounds were determined in aqueous extract of fresh plant and dried powder of portulaca oleracea. Infested rats
by toxic hepatitis were feeding orally with aqueous extract compared with silymarin drug which led to prevent the
increase of the serum hepatic enzyme level (ALP, AST and ALP), uric acid, nitric oxide, lipid profile and liver
MDA. Antioxidant status in liver GSH were declined in rats treated with Ccl4 alone, increased after feeding orally.
The histopathological examination of liver also showed that aqueous extract of portulaca oleracea reduced the
incidence of liver lesions signs of hepatic toxicity and substantiates its use in various liver disorders as hepato
protection. The results of anti-cancer activity showed the highest HEPG2 dead cell percentage by plant dried powder
(0.547 liver cell of HEPG2) at concentration of 12.50 μg/ml. Increasing the concentration to 100 μg/ml the resulted
in more higher percentage of HEPG2 dead cell (0.668) and the cytotoxic effect was determined with the Ic50 values
of 17 μg/ml in HEPG2 cell line.
Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy.
Cuphea aequipetala (Lythraceae) is a medicinal plant highly appreciated in Mexico to treat, stomach ailments such as pain and burning sensation, stomach infections, ulcers, diarrhea, dysentery, and different types of tumors and bruises. In this work, the infusion of aerial parts of this plant (CAI) was investigated for its polypharmacological potential.
In vitro anti-H. pylori activity was assessed by broth dilution method. Pharmacological studies included acute toxicity in mice using Lorke´s model, anti-inflammatory activity by xylene and TPA induced ear edema assay, as well as gastroprotection with ethanol-induced gastric ulcer model. DPPH and ABTS assays were used to determine antioxidant capacity. Polyphenols and flavonoid contents were determined by Folin-Ciocalteu method and AlCl3 reaction, respectively.
CAI showed good anti-H. pylori activity with a MIC of 125μg/mL. The infusion was not toxic according to Lorke´s model with a LD50 greater than 5g/kg. CAI exhibited low anti-edematogenic action in the models assayed. Oral administration of 300mg/kg CAI significantly reduced gastric lesions by 87.9%. The effect was reversed only by indomethacin and N-ethylmaleimide demonstrating the role of endogenous prostaglandins and sulfhydryl compounds in gastroprotection. Total phenolic and flavonoid contents of CAI were 109.9mg GAE/g DW and 28.1mg QE/g DW, respectively, and the infusion exhibited a good antioxidant activity that is thought to play a role in its biological activity. The analysis of a preliminary fractionation of the infusion indicates that the complete extract conserves all its pharmacological activities in contrast to fractionated extracts.
C. aequipetala is a promising native herb in an integral therapy for the treatment of bacterial or non-bacterial gastric ulcer because it possesses some anti-inflammatory properties, as well as exhibits good gastroprotective and antibacterial effects. It represents an important source for the isolation of anti-H. pylori compounds. This work provides ethnopharmacological evidence that supports the traditional use of this species.
The prevalence of obesity is steadily rising and has huge health and financial implications for society. Weight gain is due to an imbalance between dietary intake and energy expenditure and research has focused on trying to understand the complex pathways involved in controlling these aspects. This review highlights the key areas of research in the hypothalamic control of appetite. The hypothalamus consists of several nuclei that integrate peripheral signals, such as adiposity and caloric intake, to regulate important pathways within the CNS controlling food intake. The best characterized pathways are the orexigenic neuropeptide Y/Agouti-related protein and the anorexigenic pro-opiomelanocortin/cocaine- and amphetamine-related transcript neurons in the arcuate nucleus of the hypothalamus. These project from the arcuate nucleus to other key hypothalamic nuclei, such as the paraventricular, dorsomedial, ventromedial and lateral hypothalamic nuclei. There are also projections to and from the brainstem, cortical areas and reward pathways, all of which influence food intake. The challenge at present is to understand the complexity of these pathways and try to find ways of modulating them in order to find potential therapeutic targets.
Aloe plants have been used medicinally for centuries. Recent widespread importance
of commercial aloe vera has encouraged scientists to scientifically assess these products.
Aim
The aim of this study was to assess the possible protective role of oral commercial aloe vera on gastric mucosal acute damage induced by nonsteroidal anti-inflammatory
drugs such as diclofenac sodium.
Materials and methods
Seventy adult male albino rats were divided randomly into four groups: group I
(control), group II animals were given 200 mg/kg body weight of aloe vera once daily orally for 2 weeks, group III animals were administered a single oral dose of diclofenac
sodium (80 mg/kg body weight) to induce acute gastric damage, group IV animals
were given the same dose of aloe vera for 2 weeks followed by induction of acute
gastric damage. Stomachs of animals of the four groups were studied macroscopically
and microscopically. Morphometrical and statistical analyses were also carried out for
determination of the percentage of area and depth of the mucosal lesion.
Results
This study showed that the percentage of area and depth of the mucosal lesions were
significantly decreased in group IV in comparison with other groups. Microscopically,
group IV and group III showed exfoliation of the surface epithelium, necrosis of some
cells of the upper part of the gland, and loss of architecture of the basal part of
the gland. Moreover, in group IV, periodic acid Schiff-Alcian blue-positive mucoussecreting
cells appeared along the pits, neck, and isthmus with a thick periodic
acid Schiff-Alcian blue-positive stained surface mucous film compared with a thin
interrupted mucous film on the surface epithelium of the fundic mucosa in group III.
Ultrathin sections showed predominance of mucous secretory cells with various
types of mucoid granules in group IV.
Conclusion
Commercial aloe vera provides a degree of protection against acute gastric mucosal
damage mainly by increasing mucin secretion.
Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy.
In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy.
While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy.
Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.
Studies have been made to understand the anti-ulceral and anti-oxidant properties of the "earthworm paste" derived from Lampito mauritii (Kinberg), an indigenous species, in comparison with the standard anti-ulceral drug-ranitidine, on the Wistar strain albino rats Rattus norvegicus. Administration of 200 mg/kg aspirin was found to increase the volume of gastric juice secretion, total acidity, free acidity, ulcer index and reduce the pH. It also had decreased the anti-oxidant levels such as reduced glutathione, glutathione peroxidase, catalase, superoxide dismutase and increased the level of thiobarbituric acid reactive substances. Pretreatment with the standard drug-ranitidine (50 mg/kg) and different doses of "earthworm paste" (20, 40, 80, 160 and 320 mg/kg) in ulcer induced animal had enhanced the pH, decreased the volume of gastric juice, free acidity, total acidity and reduced the ulcer index. Further the activities of reduced glutathione, glutathione peroxidase, catalase, superoxide dismutase were increased whereas the thiobarbituric acid reactive substance had decreased. The results were more significant in rats administered with 160 mg/kg "earthworm paste" than the application of ranitidine and other doses of "earthworm paste". This indicates the presence of antiulcer and anti-oxidative effects in "earthworm paste". In conclusion, administration of 160 mg "earthworm paste"/kg was found to have better therapeutic properties.
Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults.
A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report.
The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women).
These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.
Impressive evidence has accumulated over the past 12 years indicating that one of the potentially important biophysical characteristics of mucus relates to its hydrophobic character. This surface property is region specific and reaches high values in the stomach and colon, where barrier properties against noxious agents in the lumen are most important. The hydrophobic properties of mucus appear to be related to its lipidic constituents and specifically to the presence of phospholipid surfactants that are synthesized, stored, and secreted by GI mucus cells in a regulated fashion.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are popular and important for the treatment of inflammation and pain. However, conventional NSAIDs are intrinsically toxic to the gastroduodenal (GD) mucosa. The literature can, and should, guide us towards safer prescribing of NSAIDs. Factors known to increase the risk of GD toxicity include: history of peptic ulcer disease; advanced age; high doses; and coadministration of aspirin, anticoagulants or corticosteroids. Patients with any one of these risk factors, with the possible exception of age alone, should receive gastroprotective prophylaxis with proton pump inhibitors or misoprostol. Standard dose H2 antagonists do not protect against NSAID-induced gastric ulcers and are unsuitable for prophylaxis. Awareness of risk factors and appropriate prophylactic agents will minimize the risk to patients. Whether the new generation of highly selective COX-2 inhibitors and nitric oxide-donating NSAIDs are safer drugs in long-term use be remains to be proven, though initial clinical trial data are positive.
Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC50) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.