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Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: Impact on oxidative stress, inflammation and calcitonin-gene related peptide
Abstract
The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100 mg/kg) one hour before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100 mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1β, TNF-α, 5-LO and COX-2. Additionally, the caspases-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of haemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC–PDA–ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora.
... One key morphological characteristic of many Corymbia spp. is their production of kino, a resinous exudate which is used to treat many ailments by the aboriginal peoples of Australia [17]. Along with the known ethnomedical uses of various Corymbia species, a broad range of biological activities are observed in the EOs, crude extracts and compounds isolated from this genus [18][19][20][21], highlighting the potential of the Corymbia genus to provide new drug leads and treatments for many common diseases. To date, the ethnopharmacology, phytochemistry and biological activities of the Corymbia genus have not been reviewed, and it is therefore the aim of this study to provide the first ethnopharmacological summary for this genus and outline the biological activities of Corymbia spp. ...
... Aegypti [73]; larvicidal activity of aqueous EtOH leaf extract [59]; larvicidal activity of leaf EOs against S. frugiperda larvae [74]; insecticidal activity of MeOH extract against T. castaneum [75]. Anti-Oxidant/Anti-Inflammatory Activity: leaf EO showed significant inhibition and IC50 values of 4.8-344 μg/mL in DPPH assays [31,33,[76][77][78][79][80]; floral EO showed moderate DPPH inhibition [31]; leaf EO showed potent peroxidation inhibition in a linoleic acid/β-carotene assay [33]; leaf and floral EOs showed micromolar protease inhibition [31]; anti-inflammatory properties via inhibition of LOX-1 [28]; kino EtOH extract [32] and flavanols isolated from kino exhibited 15-LOX inhibition [49]; potential anti-inflammatory and anti-viral activity of leaf EO via LOX and ACE2 inhibition [81]; potent anti-inflammatory and gastroprotective properties of ellagitannin fraction in rats [20]; potent inhibition of LPS-induced inflammation in ...
... An in vivo investigation of the anti-inflammatory and analgesic activities of the leaf EO of C. citriodora was performed in rats and showed that the EO inhibits central and peripheral nociception, as well as neutrophil-independent and neutrophil-dependent inflammation [35]. Another in vivo investigation showed the ellagitannin-rich fraction extracted from the leaves of C. citriodora had anti-inflammatory and gastroprotective effects in EtOH-induced rats [20]. This research was expanded upon, wherein the ellagitannin ellagic acid 3 ( Figure 12) was isolated from the leaves of C. citriodora and shown to have significant anti-inflammatory (increased IL-10 and PGE2 levels and decreased IL-6, TNFα and COX-2 levels) and anti-gastric ulcer effects in EtOH-induced mice [39]. ...
Plants have been vital to human survival for aeons, especially for their unique medicinal properties. Trees of the Eucalyptus genus are well known for their medicinal properties; however, little is known of the ethnopharmacology and bioactivities of their close relatives in the Corymbia genus. Given the current lack of widespread knowledge of the Corymbia genus, this review aims to provide the first summary of the ethnopharmacology, phytochemistry and bioactivities of this ge-nus. The Scopus, Web of Science, PubMed and Google Scholar databases were searched to identify research articles on the biological activities, phytochemistry and ethnomedical uses of Corymbia species. Of the 115 Corymbia species known, 14 species were found to have ethnomedical uses for the leaves, kino and/or bark. Analysis of the references obtained for these 14 Corymbia spp. revealed that the essential oils, crude extracts and compounds isolated from these species possess an array of biological activities including anti-bacterial, anti-fungal, anti-protozoal, anti-viral, larvicidal, insec-ticidal, acaricidal, anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic activities, highlighting the potential for this under-studied genus to provide lead compounds and treatments for a host of medical conditions.
... At day 30, after the final administration, all rats were fasted for 24 h but given free access to water. Then rats were gavage with absolute ethanol at 5 mL/kg body weight to induce gastric ulceration based on reference to other research and pre-experiment [8,[25][26][27][28]. One hour later, animals were sacrificed, a blood sample was collected from the femoral artery and then centrifuged at 3000 rpm for 15 min to obtain serum and preserved at −80 • C; the stomach was immediately removed, and the gastric juice was collected into a tube and then the pH of gastric content was recorded with a digital pH meter. ...
... Most studies of ethanol-induced gastric mucosal damage have been performed in rodent models, but there is no generally accepted gavage dose of alcohol to date. According to multiple pieces of literature, absolute ethanol administered at a dose of 5 mL/kg in rodents was used more frequently, and the gastric mucosa injury can occur about 30 min and generally reach a peak 60 min after alcohol intake, which took into account differences in alcohol metabolism between rodents and humans [8,[25][26][27][28]. In pre-experiments, we found that the dose of absolute ethanol caused obvious damage to gastric mucosa with low mortality of rats. ...
... Oxidative stress has been suggested to be involved in the pathogenesis of gastric mucosal damage caused by ethanol, which is due to the imbalance between the substantial production of reactive oxygen species (ROS) and rapid depletion of endogenous antioxidant capacity [6,49]. A chief source of oxygen free radicals generation could be ascribed to the infiltration of neutrophils, and it is closely related to the imbalance of cellular homeostasis and the excessive production of lipid peroxides [26]. The impairment of antioxidant defense mechanisms was induced by ethanol basically through enhancing the generation of cellular oxidants (e.g., O2•−) and lipid peroxidation products (e.g., MDA) and depleting the number of antioxidants (e.g., SOD, GSH, CAT) in the gastric mucosa, which in turn causes mitochondrial membrane changes in permeability and depolarization, and eventually led to cell death and apoptosis [5,50]. ...
The study investigated the protective effect of walnut oligopeptides (WOPs) against ethanol-induced gastric injury using Sprague-Dawley (SD) rats. Rats were randomly divided into seven groups based on body weight (10/group), normal group, ethanol group, whey protein group (220 mg/kg body weight), omeprazole group (20 mg/kg body weight), and three WOPs groups (220, 440, 880 mg/kg body weight). After 30 days of treatment with WOPs, rats were given 5 ml/kg absolute ethanol by gavage to induce gastric mucosal injury. Gastric ulcer index (GUI) were determined and the following measured; gastric content pH, gastric mucin, endogenous pepsinogens (PG), prostaglandin E2 (PGE2), inflammatory cytokines, oxidative stress indicators, and the expression of apoptosis-related proteins were measured to evaluate the gastroprotective effect of WOPs. The results showed that the administration with WOPs markedly mitigated the hemorrhagic gastric lesions caused by ethanol in rats, and decreased the GUI, the gastric content pH, PG1, PG2, and NO levels, enhanced mucin and PGE2. Also, WOPs repressed gastric inflammation through the reduction of TNF-α, IL-6, IL-1β and increase IL-10 levels, and revealed antioxidant properties with the enhancement of superoxide dismutase, glutathione, and catalase activity, while reduction of malondialdehyde. Moreover, WOPs treatment significantly down-regulated Bax, caspase-3 and nuclear factor-κB p65 (NF-κB p65) expression, while up-regulating the expression of Bcl-2 and inhibitor kappa Bα (IκBα) protein. These results indicated that WOPs have protective effects against ethanol-induced gastric mucosal injury in rats through anti-inflammatory, anti-oxidation, and anti-apoptosis mechanisms.
... Upon increasing casuarinin dosage, the gastric acidity is decreased due to an increase in the mucin content, as well as a marked inhibition of gastric oxidative stress and inflammation in comparison with the lower doses of casuarinin. This effect is really crucial for the protection of gastric mucosa because mucus represents the first line of defense against injurious factors [2,4,27]. These protective effects of casuarinin were attributed to its stimulant effect on PGE2 production, which protects gastric mucosa by promoting gastric mucus and bicarbonate secretion, along with improving blood flow [28,29]. ...
... The rest of the groups, Groups IV-VI, were orally administered with a single dose of 25, 50, and 100 mg/kg of casuarinin, respectively. Dose selection for casuarinin was based upon preliminary studies in our lab-oratory and in agreement with other studies reporting the gastroprotective effect of ellagitannins [27]. After 1 h, to induce gastric ulceration, absolute ethanol (5 mL/kg orally) was given to all groups except Group I. Animals were left for 1 h after ethanol administration, anesthetized using ketamine hemisulfate (100 mg/ kg, i. p.), and then sacrificed by decapitation. ...
... A digital camera was used to take photographs (10-megapixel 5 × zoom). The appearance of hemorrhagic lesion bands indicated ethanol-induced ulcer [27,30]. Image analysis software (Image J, 1.46a) was used to calculate areas of ulcerated lesions. ...
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.
... Groups III, IV, and V were given aqueous ethanol extract of R. spiciforme at doses of 125, 250, and 500 mg/kg body weight once per day for 7 days, respectively [14] . Gastric ulcer was induced by administering ethanol (5 mL/kg) to rats after 1-h pre-treatment with crude extract and omeprazole on day 7 [15] . ...
... Groups III, IV, and V were treated with butanol, aqueous, and dichloromethane fractions of plant extract at 250 mg/kg once per day for7 days. Then, gastric ulcer was induced in adherence to protocols briefly mentioned in section 2.5 [15] . ...
Helicobacter pylori infection, pepsin, ischemia, hypoxia, smoking, alcohol intake, hydrochloric acid, and nonsteroidal anti-inflammatory drugs are the causal factors of ulceration. In third-world countries, approximately one in two individuals has signs of gastric ulceration. Extensive literature suggested that plant-derived drugs hold the potential in the treatment of peptic ulcer, and Rheum spiciforme (family: Polygonaceae) has been known in the folk medicine for possessing medicinal effect on ulceration. To explore further along this line, the current study was designed to investigate the effects of aqueous ethanol extract of R. spiciforme roots and its fractions on peptic ulcer and to identify bioactive compounds responsible for mitigating this pathological condition. Animal model of ethanol-induced gastric ulcer was utilized in this study. The animals were pre-treated with crude plant extract, given at doses 125, 250, and 500 mg/kg, and then orally administered with butanol, aqueous, and dichloromethane fractions at doses of 250 mg/kg for 7 days. Following the treatments, a significant decrease in ulcerative lesions, ulcer index, ulcer severity score, volume, free acidity, and total acidity of gastric juice as well as a marked increase of gastric pH in the groups treated with plant extract at doses of 250 and 500 mg/kg were noted. Moreover, butanol fraction has been shown to produce effects equipotent to that of the reference drug omeprazole. Liquid chromatography-mass spectrometry analyses show that the plant extract contains emodin, aloe-emodin, and quercetin. In conclusion, this study demonstrated that the aqueous ethanol extract of R. spiciforme and its butanol fraction exhibited gastro-protective effect.
... Recent studies also reported that E. citriodora protects β-cells damaging by inhibiting protein glycation via free radical scavenging [47]. Another study with E. citriodora indicated antioxidant properties, and it might help to overcome oxidative stress-induced protein damage [20,48,49]. Plants containing flavonoids, such as procyanidin, epicatechin, and rhodomyrtosone E, have also been indicated to have anti-glycation properties in recent studies [8,22,23]. ...
... Postprandial hyperglycaemia is considered to be a risk factor for CVD, and thus treating postprandial may prevent secondary cardiovascular complications in type 2 diabetic patients [50]. Inhibition of α-amylase and α-glucosidase activities are an essential strategy for managing postprandial hyperglycemia and the inhibition of these enzymes might be beneficial to type 2 diabetes patients with impaired insulinotropic response [49]. In the present studies, EEEC significantly inhibited starch hydrolysis in a concentrationdependent manner. ...
Due to the numerous adverse effects of synthetic drugs, researchers are currently studying traditional medicinal plants to find alternatives for diabetes treatment. Eucalyptus citriodora is known to be used as a remedy for various illnesses, including diabetes. This study aimed to explore the effects of ethanol extract of Eucalyptus citriodora (EEEC) on in vitro and in vivo systems, including the mechanism/s of action. The methodology used involved the measurement of insulin secretion from clonal pancreatic β-cells, BRIN BD11, and mouse islets. Other in vitro systems further examined EEEC’s glucose-lowering properties. Obese rats fed a high-fat-fed diet (HFF) were selected for in vivo evaluation, and phytoconstituents were detected via RP-HPLC followed by LC-MS. EEEC induced insulin secretion in a concentration-dependent manner with modulatory effects, similar to 1 µM glucagon-like peptide 1 (GLP-1), which were partly declined in the presence of Ca2+-channel blocker (Verapamil), KATP-channel opener (Diazoxide), and Ca2+ chelation. The insulin secretory effects of EEEC were augmented by isobutyl methylxanthine (IBMX), which persisted in the context of tolbutamide or a depolarizing concentration of KCl. EEEC enhanced insulin action in 3T3-L1 cells and reduced glucose absorption, and protein glycation in vitro. In HFF rats, it improved glucose tolerance and plasma insulin, attenuated plasma DPP-IV, and induced active GLP-1 (7-36) levels in circulation. Rhodomyrtosone B, Quercetin-3-O-β-D-glucopyranoside, rhodomyrtosone E, and quercitroside were identified as possible phytoconstituents that may be responsible for EEEC effects. Thus, these findings revealed that E. citriodora could be used as an adjunct nutritional supplement to manage type 2 diabetes.
... An ellagitannin fraction attained from EO has been examined against an ethanol-induced acute gastric ulcers in rats. Its gastric protective influence could be intermediated by ameliorating ethanol-induced gastric oxidative stress (41) . Ellagitannin-pre-treatment protected against gastric ulcers, significantly augmented the exhausted GSH and SOD levels and reduced the raise in MDA in gastric tissue. ...
... Ellagitannin-pre-treatment protected against gastric ulcers, significantly augmented the exhausted GSH and SOD levels and reduced the raise in MDA in gastric tissue. The results confirmed a preceding study which stated that ellagitannin exerted a prevailing anti-inflammatory power as showed by a decline in the inflammatory cytokines; TNF-α and IL-1β (41) . ...
Background: Eucalyptus oil often used for medicinal purposes. Aims: The Eucalyptus oil gastro protective impact investigated against gamma-rays-exposure-induced gastric ulceration in rats. Methods: Thirty-two rats were divided equally into 4groups; control, Eucalyptus oil (100mg/ kg), gamma-rays (7Gy) and Eucalyptus oil plus gamma-rays treated groups. The stomach histopathology samples were examined. The levels of malondialdehyde, reduced glutathione, superoxide dismutase, tumour necrosis factor-α and the interleukin-1β were assessed. Results: The stomach histopathological examination revealed that pre-treatment with Eucalyptus oil enhanced regeneration of mucosal crypt cells. The results revealed a decreased level of stomach malondialdehyde, inflammatory markers, increased levels of stomach antioxidants markers in Eucalyptus oil plus gamma-rays treated group. Conclusion: Eucalyptus oil ameliorates gamma-rays-induced gastric ulceration that could attribute to its antioxidant, anti-apoptotic and radioprotective activities.
... vitamin E) reversed the oxidative stress effect of OME and inhibited its genotoxic and mutagenic effects (Guduru and Rohit, 2016;Braga et al., 2018Braga et al., , 2021Paz et al., 2020). Conversely, OME has been reported to increase in-vivo antioxidant levels and capacity (Koch et al., 2002;Biswas et al., 2003;Ganguly et al., 2006;Al-Sayed et al., 2015). This suggests a contradictory antioxidant effect of OME as reported in literature. ...
Despite the widespread use of omeprazole (OME), there are still concerns about its long-term safety and tolerability, especially with long-term or indiscriminate use. This study was designed to evaluate the effect of 90 days sub-chronic administration of OME on haematological, biochemical, antioxidant, reproductive and histopathological parameters in male and female rats. Forty-eight (48) Wistar rats of both sexes were divided into 4 groups of 6 male and 6 female animals each. Group I received 10 mL/kg normal saline, while Groups II – IV received 0.12 mg/kg, 0.57 mg/kg, 2.85 mg/kg of OME respectively for 90 days. At the end of 90 days, 5 mL blood sample was collected, and vital organs were harvested for relevant analyses. In this study, OME did not elicit any significant (P>0.05) change in the body weight or weight of vital organs, but elicited a significant (P<0.05) reduction in sperm count at the supratherapeutic dose (2.85 mg/kg). The supratherapeutic dose of OME produced significant increase in cholesterol (P<0.0001) and LDL (P<0.0001) in female rats. OME did not generally produce a significant change in haematological parameters. OME elicited a significant decrease in CAT (P<0.05) in female and combined animals. Additionally, histopathological presentations of vital organs were generally non-abnormal. From this study, it can be concluded that long term administration of OME is generally safe and tolerable, especially at lower doses. Findings from this study suggest that OME may potentially induce changes in sperm characteristics (in relation to male rats), hepatoxicity, hypercholesteremia, hyperlipidemia and thrombocytosis over a long duration, at higher doses and especially in female animals.
... For instance, the long-term use of PPI and H2RA can affect the body's absorption of vitamin B12 and increase the risk of developing bacterial peritonitis [8,9]. In summary, it is necessary to seek natural, nontoxic substances that can effectively enhance the gastric mucosal barrier and improve gastrointestinal function, such as polysaccharides and food-derived bioactive peptides; research has shown that wheat peptides and calcitonin-gene-related peptides have protective mechanisms against ethanol-induced gastric ulcers in rats [10][11][12][13]. ...
The objective of this research was to explore the protective impact of walnut peptides (WP) against ethanol-induced acute gastric mucosal injury in mice and to investigate the underlying defense mechanisms. Sixty male BALB-c mice were divided into five groups, and they were orally administered distilled water, walnut peptides (200 and 400 mg/kg bw), and omeprazole (20 mg/kg bw) for 24 days. Acute gastric mucosal injury was then induced with 75% ethanol in all groups of mice except the blank control group. Walnut peptides had significant protective and restorative effects on tissue indices of ethanol-induced gastric mucosal damage, with potential gastric anti-ulcer effects. Walnut peptides significantly inhibited the excessive accumulation of alanine aminotransferase (ALT), aspartate transferase (AST), and malondialdehyde (MDA), while promoting the expression of reduced glutathione (GSH), total antioxidant capacity (T-AOC), glutathione disulfide (GSSG), and mouse epidermal growth factor (EGF). Furthermore, the Western blot analysis results revealed that walnut peptides significantly upregulated the expression of HO-1 and NQO1 proteins in the Nrf2 signaling pathway. The defensive impact of walnut peptides on the gastric mucosa may be achieved by mitigating the excessive generation of lipid peroxides and by boosting cellular antioxidant activity.
... Ellagitannin-rich fraction increased the levels of Superoxide dimutase and Glutathione in rats with an ethanol-induced gastric ulceration model (Al-Sayed & El-Naga, 2015). ...
A peptic ulcer is a prevalent gastrointestinal disorder affecting a significant proportion of the global population. The use of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) to cure inflammations can lead to recurrent and serious gastrointestinal bleeding and ulceration. Disruption of mucosal resistance to an injury can be caused by two major factors: NSAIDs and Helicobacter pylori infection. Even in modern times, herbal medicine remains a widely used primary healthcare option, particularly in developing countries, due to its perceived compatibility with the human body and lower incidence of side effects. Numerous medicinal plants and dietary nutrients have been found to exhibit gastro-protective properties, including aloe, terminalia chebula, ginseng, capsicum, and others. The key objectives of peptic ulcer disease management are to alleviate pain, facilitate ulcer healing, and delay its recurrence. This chapter assesses the anti-ulcer potential of medicinal plants.
... The imbalance between the considerable formation of reactive oxygen species (ROS) and the quick depletion of endogenous antioxidant capacity has been reported to be implicated in the aetiology of gastric mucosal injury produced by ethanol (Liu et al. 2020). The infiltration of neutrophils is a major source of oxygen free radicals, and it is intimately linked to the disruption of cellular homeostasis and the excessive creation of lipid peroxides (Al-Sayed and El-Naga 2015). Ethanol impairs antioxidant defense mechanisms by increasing the production of cellular oxidants and lipid peroxidation products and depleting the number of antioxidants inside the gastric mucosa, which leads to changes in mitochondrial membrane permeability and depolarisation, eventually leading to cell death and apoptosis (Golbabapour et al. 2013). ...
Context:
Gastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.
Materials and methods:
Chemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analyzed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.
Results:
UPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signaling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.
Conclusion:
Present results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.
... Extreme ingestion of ethanol provokes inflammation with the release of inflammatory cytokines as well as macrophages and lymphocytes infiltrated to the inflammation site [37,38]. The infiltrating of immune cells, especially neutrophils results in connexin destruction and mucosal barrier damage, which ultimately leads to gastritis [39]. ...
Extreme ethanol ingestion is associated with developing gastric ulcers. Achillea millefolium (yarrow) is one of the most commonly used herbs with numerous proven pharmacological actions. The goal of the hereby investigation is to explore the gastroprotective action of yarrow essential oil against ethanol-induced gastric ulcers and to reveal the unexplored mechanisms. Rats were distributed into five groups (n = 6); the control group administered 10% Tween 20, orally, for two weeks; the ethanol group administered absolute ethanol (5 mL/kg) to prompt gastric ulcer on the last day of the experiment. Yarrow essential oil 100 or 200 mg/kg + ethanol groups pretreated with yarrow oil (100 or 200 mg/kg, respectively), orally, for two weeks prior to gastric ulcer induction by absolute ethanol. Lanso + ethanol group administered 20 mg/kg lansoprazole, orally, for two weeks prior to gastric ulcer induction by ethanol. Results of the current study showed that ethanol caused several macroscopic and microscopic alterations, amplified lipid peroxidation, pro-inflammatory cytokines, and apoptotic markers, as well as diminished PGE2, NO, and antioxidant enzyme activities. On the other hand, animals pretreated with yarrow essential oil exhibited fewer macroscopic and microscopic modifications, reduced ulcer surface, and increased Alcian blue binding capacity, pH, and pepsin activity. In addition, yarrow essential oil groups exhibited reduced pro-inflammatory cytokines, apoptotic markers, and MDA, restored the PGE2 and NO levels, and recovered the antioxidant enzyme activities. Ethanol escalated Nrf2 and HO-1 expressions, whereas pretreatment of yarrow essential oil caused further intensification in Nrf2 and HO-1. To conclude, the current study suggested yarrow essential oil as a gastroprotective agent against ethanol-induced gastric lesions. This gastroprotective effect could be related to the antioxidant, anti-inflammatory, and anti-apoptotic actions of the essential oil through the instigation of the Nrf2/HO-1 pathway.
... Symptoms of GU may include one or more of the following: bloating, abdominal pain, loss of appetite, weight loss, nausea, and vomiting. e pathogenesis of GU is complicated, and although its exact pathophysiological mechanism is not completely clear, it is well known that GU is mainly caused by the imbalance of gastric invasiveness and defensive factors [4,5]. e disease can be caused by a variety of endogenous and exogenous causes, such as Helicobacter pylori infection, gastric hyperchloremia, gastric mucosal ischemia, poor diet, stress, smoking, long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), and excessive alcohol consumption [6][7][8][9]. ...
Background:
Shaoyao-Gancao decoction (SGD) is a classic prescription in traditional Chinese medicine. SGD is effective in the treatment of gastric and duodenal ulcers. However, the biological activity and possible mechanisms of SGD in the treatment of gastric ulcers have not been fully elucidated. The purpose of this study was to scientifically evaluate the protective effect and potential mechanism of SGD against ethanol-induced gastric ulcers in rats.
Methods:
A single gavage of 10 mL/kg of 75% ethanol was used to establish a rat gastric ulcer model. A histopathological examination of the gastric tissue was performed. The levels of TNF-α, EGF, PGE2, SOD, and TBARS in gastric tissue were measured by ELISA. Cellular apoptosis in gastric tissues was assessed by TUNEL assay. The expression levels of caspase-3 and Bcl-2 were determined by immunohistochemistry. The potential mechanism of SGD in treating gastric ulcers was further studied using a network pharmacology research method.
Results:
The gastric tissue of rats with ethanol-induced gastric ulcers had obvious injury throughout the mucosal layer, which was significantly weakened in rats treated with SGD. Furthermore, treatment with SGD significantly increased the levels of EGF, PGE2, SOD, and Bcl-2 and decreased the levels of TNF-α, TBARS, and caspase-3 in the gastric tissue of rats with ethanol-induced gastric ulcers. SGD reduced ethanol-induced cell apoptosis in gastric tissue from rats with gastric ulcers. A traditional Chinese medicine-based network pharmacology study revealed that SGD exerts its anti-gastric ulcer effect by acting on multiple pathways.
Conclusions:
The above results indicate that SGD can improve gastric ulcers induced by ethanol. Moreover, this study demonstrated multicomponent, multitarget, and multipathway characteristics of SGD in the treatment of gastric ulcers and provided a foundation for further drug development research.
... [94] Ellagitannin-richfraction reduces ulceration in rats with ethanol-induced gastric ulceration model through empoweringgastric protective factors. [95] DISCUSSION Peptic ulcer is common disorder of GIT but tend to severe if kept untreated. The pharmacotherapy applied to treat ulcer can cure it but in between therapy or after the therapy the produces side effect that are harmful. ...
... Evaluation of Ethanol-Induced Gastric Ulcer. e experiment was conducted according to the methods prescribed in the studies by Morimoto et al. [19] and Al-Sayed, and El-Naga [20]. All doses were based on those described by Boeing et al. [21]. ...
Taraxacum officinale F.H. Wigg. belonging to the family Asteraceae is an edible medicinal plant distributed worldwide. This study aimed to determine the gastroprotective effects of aqueous extract of T. officinale (AETo) in rats using ultrasound, histological, and biochemical analyses. In this study, gastric ulceration was induced by ethanol or piroxicam. Rats were then treated with AETo (3, 30, or 300 mg/kg). The area and histological appearance of gastric ulcers were quantified, and histochemical analysis was performed. The activity of AETo on inflammatory and oxidative stress markers was assessed in the ulcerated tissue. In addition, we investigated the thickness of the gastric wall using the ultrasound technique. Moreover, chemical analyses of AETo were performed. In rats with ethanol- or piroxicam-induced ulcers, AETo reduced the ulceration area, elevated mucin level, and the gastroprotective effect was confirmed by histological analysis. The gastroprotective effect was accompanied by increased activities of SOD, CAT, and GST, as well as an increase in GSH level and reduction in MPO activity. Furthermore, AETo reduced the thickness of the gastric wall in rats. Phytochemical analysis of AETo indicated phenolic acids and flavonoids as the main active compounds. In conclusion, the gastroprotective effect of AETo involves reduction in oxidative stress and inflammatory injury and increase in mucin content. This study advances in the elucidation of mechanisms of gastric protection of T. officinale, contributes to the prospection of new molecules gastroprotective, and proposes the ultrasonographic analyses as a new gastroprotective assessment tool in preclinical studies.
... There are several pathogenic and aggravating factors contributing to gastric ulcers, such as Helicobacter pylori infection (Peterson 1991), long-term use of non-steroidal anti-inflammatory drugs (Matsui et al. 2011), stressful mental states (Zhao et al. 2018), excessive gastric acid secretion (Wijeratne et al. 2015) and genetic predisposition (Tahara et al. 2007). The type of gastric ulcer induced by ethanol tends to erode the gastric tissue, causing extreme damage to the gastric mucosa, including haemorrhagic damage to the gastric mucosal lesions and mucosal oedema (Park et al. 2008), inflammatory cell infiltration (Xie et al. 2017) and diffuse ulcers (Al-Sayed and El-Naga 2015). NF-jB is one of the important transcription factors regulating the development of gastric ulcer. ...
Context
Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases.
Objective
To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro.
Materials and methods
In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1β was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test.
Results
F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1β, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC50) of F-AOH on cell damage was 17 μg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1β and iNOS proteins.
Conclusions
F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.
... It should also be noted that pre-treatment with ellagitannin-rich fraction obtained from Eucalyptus citriodora, at a dose of 100 mg/kg, resulted in higher gastroprotection (99.6% in ethanol-induced acute gastric ulceration) than that of the omeprazole, a widely known proton pump inhibitor. Notably, the authors point out that ETs were found to be the major active components responsible for the marked antioxidant, anti-inflammatory and gastroprotective properties [139]. ...
Ellagitannins (ETs), characterized by their diversity and chemical complexity, belong to the class of hydrolysable tannins that, via hydrolysis under acidic or alkaline conditions, can yield ellagic acid (EA). They are mostly found as a part of extractives in angiosperms. As known antioxidants and chelators, EA and EA derivatives are drawing an increasing interest towards extensive technical and biomedical applications. The latter ones include possible antibacterial, antifungal, antiviral, anti-inflammatory, hepato- and cardioprotective, chemopreventive, neuroprotective, anti-diabetic, gastroprotective, antihyperlipidemic, and antidepressant-like activities, among others. EA’s synthesis and production challenges prompt further research on new methods and alternative sources. Conventional and prospective methods and raw materials for the production of EA and its derivatives are reviewed. Among the potential sources of EA, the residues and industrial streams of the pulp industry have been highlighted and considered as an alluring alternative in terms of commercial exploitation.
... Ethanol consumption may stimulate the innate immune system, leading to the release of pro-inflammation cytokines such as IL-6 and TNF-α. Furthermore, inhibition of inflammation mediators was beneficial for the healing of gastric ulcer [28]. Proinflammatory cytokines, especially TNF-α, is one of the aggressive factors in the development of inflammation, injury, and carcinogenesis in a variety of tissues including gastric ulcer. ...
In study, we aimed to determine the mechanisms underlying the gastroprotective effects of sodium copper chlorophyllin (SCC) against ethanol-induced gastric ulcer injury in mice. First, the gastroprotective effects of SCC against gastric ulcer induced by ethanol were assessed. Then, biochemical, histopathological, immunohistochemistry assays, and western blot analysis were conducted to determine the possible mechanisms of action underlying the effects of SCC. Compared to the effects of omeprazole (OME) in a confirmed mouse model of ethanol-induced gastric ulcer injury, treatment with various doses of SCC resulted in up-regulation of Bcl-2 and down-regulation of the pro-apoptotic protein Bax. Significant decreases in the levels of the malondialdehyde (MDA), myeloperoxidase (MPO), and NO in the gastric tissues were observed. Furthermore, inflammatory cytokine analysis revealed that SCC treatment inhibited the expressions of TNF-α and IL-6, greatly reduced the phosphorylation level of IκB, and repressed the nuclear translocation of NF-κB p65, which demonstrated that SCC inhibited the activation of the NF-κB pathway. The present findings suggest that the protective effects of SCC may be beneficial as a potential preventive and therapeutic agent for gastric ulcer through the NF-κB pathway. Taken together, SCC administration significantly decreased the levels of MPO, NO, and MDA in gastric tissue and exerted a powerful anti-inflammatory activity as demonstrated by reduction in the secretions of proinflammatory mediators such as IL-6 and TNF-α in the serum of mice exposed to ethanol.
... The Acid concentration (mEq/l) in each sample was determined by titration against 0.01 N sodium hydroxide solution, with phenolphthalein as an indicator, till reaching the endpoint [5]. Quantitative assay of the gastric mucin content was implemented according to the methodology of Al-Sayed and El-Naga (2015) [27], and was expressed as mg/ml hexoses. ...
Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole.
... [6] Excessive ethanol ingestion may also develop gastric ulcer [7] by damaging the vascular endothelium lining of the stomach and aggravates inflammatory responses causing ischemia. [8] Nonsteroidal anti-inflammatory drugs and smoking have been considered to be the main cause of peptic ulcer; hence, limited research has been focused on the lead molecules to be developed as an antiulcer agent. [9] Drugs such as antacids, anticholinergics, H 2 -receptor antagonists, and proton pump inhibitors have been developed synthetically that act specifically for preventing or treating gastric ulcers. ...
Background: Formononetin (FMN), one of the major isoflavones in red clover, has been shown to possess antioxidant, anti-inflammatory, antitumor, neuroprotective, and cytoprotective activities. However, there is no report on the gastroprotective effect of FMN against ethanol-induced gastric ulcer. Objective: Excessive alcohol consumption can lead to gastric ulcer, and the purpose of the present study was to examine the protective effect of FMN on mucosal lesions induced by ethanol. Materials and Methods: Fasted rats were orally administered with FMN at different doses, omeprazole (20 mg/kg), followed by intragastrical ingestion of ethanol (5 ml/kg) after 1 h and sacrificed after 1 h of exposure. Gross microscopic, macroscopic, and biochemical assays were scrutinized. Results: Compared with ethanol, FMN pretreatment showed a significant increase in the gastric levels of glutathione while decreased the malondialdehyde content remarkably. FMN pretreatment also bestowed the cytoprotective efficacy against ethanol-induced ulceration by reestablishing the decreased level of nitrite (NO). Furthermore, in histopathological sections, reduced pathological changes of gastric lesions were markedly observed in the FMN-pretreated groups compared with those in the ethanol group. Western blot analysis showed upregulation of BcL 2 while downregulation of Bax in FMN-pretreated gastric tissue of rats. Conclusion: These results indicate that FMN exerts gastroprotective effects through the antioxidative, anti-inflammatory, and antiapoptotic that are probably mediated by enhanced NO release, suggesting its therapeutic use to treat gastric ulceration by preserving mucosal glycoproteins and diminishing oxidative stress. © 2019 Pharmacognosy Magazine Published by Wolters Kluwer - Medknow.
... These results suggest that acute dosage of WAP is safe on the gastrointestinal tissue when compared with indomethacin. NSAIDs are highly associated with gastrointestinal distress causing peptic ulceration and bleeding (Al-Sayed and El-Naga, 2015). ...
... Experimental evidence indicates that ellagitannins confer potent radical scavenging activity and inhibitory effect on lipid peroxidation (Al-Sayed, El-Lakkany, Seif El-Din, Sabra, & Hammam, 2014;Shimoda et al., 2008). Previous reports have demonstrated that ellagitannins protect against the liver injury induced by free radicals through different mechanisms, including direct radical scavenging, metal chelation, and enhancement of antioxidant defenses such as superoxide dismutase (SOD) and glutathione (GSH; Al-Sayed & El-Naga, 2015). These attributes prompted us to determine the hepatoprotective activity of praecoxin A, an ellagitannin compound isolated from Melaleuca ericifolia Sm. (Myrtaceae). ...
The hepatoprotective activity of praecoxin A, an ellagitannin from Melaleuca ericifolia, was determined against CCl4‐induced toxicity in mice. Praecoxin A was administered (25, 50, and 100 mg/kg) for 5 days followed by CCl4. Praecoxin A markedly ameliorated the CCl4‐induced increase in AST (by 19, 52, and 56%), ALP (22, 45, and 48%), ALT (11, 47, and 54%), total bilirubin (14, 27, and 28%), and MDA (26, 44, and 51%) at the tested doses, respectively, as compared with CCl4 group. It was evident that praecoxin A significantly (p < 0.001) increased the antioxidant parameters GSH (45, 99, and 137%) and SOD (61, 129, and 159%). Histological findings revealed a marked amelioration of hepatocyte degeneration, necrosis, inflammatory cell infiltration, and hemorrhage in the groups treated with praecoxin A. COX‐2 and caspase‐3 hepatic expressions were significantly downregulated (p < 0.001) in praecoxin A‐treated groups (up to 57, 83, and 93% for COX‐2 and by 30, 82, and 99% for caspase‐3). These findings suggest that praecoxin A exerts a beneficial effect against oxidative stress by reducing lipid peroxidation, enhancing the antioxidant defense status, and protecting against the histopathological changes induced by CCl4. This study highlights a promising natural hepatoprotective candidate derived from M. ericifolia that might be an alternative to silymarin.
... steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are other factors considered as proponents of gastric ulcer [17]. In Africa and most part of the world, herbs concocted locally have been claimed to be effective in preventing or protecting against stomach ulceration [18][19][20][21]. In south west part of Nigeria, particularly among the Yoruba indigenes, a polyherbal formulation (PM) composed of Adenopus breviflorus, Pterocarpus osun and potassium ash has been widely used and acclaimed to be a viable anti-ulcerative agent. ...
... Una úlcera iende como una lesión de carácter crónico y recurrente que se caracteriza por la pérdida de integridad y presencia de un proceso inflamatorio en la mucosa gástrica o intestinal [4,5,6]. La fisiopatología de las úlceras gástricas se atribuye al desbalance corrosivos y los mecanismos de gastroprotección de la mucosa gástrica, los cuales incluyen una adecuada motilidad gastrointestinal y perfusión gástrica, una barrera de moco continua e intacta y mediadores bioquímicos como las prostaglan y el óxido nítrico [7,8]. ...
Licania platypus is a species widely distributed in tropical countries. Traditionally, it has been used in Central America for a variety of health problems, especially gastrointestinal problems.
Aim: To investigate gastric antiulcer activity and gastrointestinal motility effect of Licania platypus leaves aqueous extract.
Methods: Gastric lesions were induced by ethanol and indomethacin models; also other parameters were analyzed in pylorus-ligated model. Furthermore, was evaluated the effect on gastrointestinal motility using phenol red.
Results: Oral administration of aqueous extract (1000 mg/kg) significantly reduced the area of gastric lesions (p < 0,05) on both models. It was observed a significantly increased the gastric secretion volume and gastric mucus, whereas decreased total acidity and lipid peroxidation (p < 0,05). The aqueous extract of Licania platypus reduced the rate of gastric emptying (p < 0,05), but did not show any effect on intestinal transit.
Conclusion: Licania platypus aqueous extract has a gastroprotective effect in different acute ulcer induction models and reducing the rate of gastric emptying. The activities proved in this study contribute
ethnopharmacological knowledge attributed to Licania platyus.
... Tannins fraction of Mouriri pusa augmented cell proliferation, anti-inflammatory activity by reducing COX-2 levels, enhanced angiogenesis and increased mucus secretion [176]. Ellagitannin-rich fraction increased GSH and SOD levels in rats with ethanol-induced gastric ulceration model [175]. Hydroalcoholic extract from Persea major bark exerted antiulcer effects in rodents through empowering gastric protective factors. ...
In this narrative review, we have comprehensively reviewed the plant sources used as antiulcer agents. From traditional uses as herbal remedies, we have moved on to preclinical evidence, critically discussing the in vitro and in vivo studies focusing on plant extracts and even isolated phytochemicals with antiulcerogenic potential. A particular emphasis was also paid to Helicobacter pylori activity, with emphasis on involved mechanisms of action. Lastly, the issue of safety profile of these plant products has also been addressed.
... steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are other factors considered as proponents of gastric ulcer [17]. In Africa and most part of the world, herbs concocted locally have been claimed to be effective in preventing or protecting against stomach ulceration [18][19][20][21]. In south west part of Nigeria, particularly among the Yoruba indigenes, a polyherbal formulation (PM) composed of Adenopus breviflorus, Pterocarpus osun and potassium ash has been widely used and acclaimed to be a viable anti-ulcerative agent. ...
... steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are other factors considered as proponents of gastric ulcer [17]. In Africa and most part of the world, herbs concocted locally have been claimed to be effective in preventing or protecting against stomach ulceration [18][19][20][21]. In south west part of Nigeria, particularly among the Yoruba indigenes, a polyherbal formulation (PM) composed of Adenopus breviflorus, Pterocarpus osun and potassium ash has been widely used and acclaimed to be a viable anti-ulcerative agent. ...
Abstract
Aim: In view of folklore usage and therapeutic claims, the anti-ulcerative potential of a formulated polyherbal mixture (PM) containing Adenopus breviflorus, Pterocarpus osun and potassium ash was assessed in indomethacin-induced rat model, using Cimetidine as a reference drug.
Material and Methods: Twenty-four male adult Wistar rats were randomized into four study groups (n=6) as follows: (1) normal control, (2) indomethacin control (3) Indomethacin and Cimetidine treated (4) Indomethacin and PM treated. Indomethacin was administered via intraperitoneal (i.p) route at a dosage of 40mg/kg of body weight (BW), preceded by oral (p.o) treatments of groups 3 and 4 animals with Cimetidine and PM respectively, twice daily at 8 h interval for 7 days.
Results: PM-pre-treated animals showed significant improvement against indomethacin-induced ulceration vis-à-vis the evaluated indices (gastric volume, free acidity, total acidity and pepsin activity). This is evident by the photomicrographs of the stomach linings of the PM-treated animals when compared to those of indomethacin-control group. However, the anti-ulcerative effect of PM was significantly lower than that expressed by Cimetidine, a known anti-ulcerative drug.
Conclusions: The results obtained in this study apparently lend credence to the folklore anti-ulcerative claim on PM. Nonetheless, it is necessary to carry out both acute and repeated dose toxicity studies on the `drug mixture` to ascertain its herbal safety before any recommendations regarding its use as an anti-ulcerative agent is made.
Keywords: Polyherbal mixture; Adenopus breviflorus; Pterocarpus osun; Potassium ash; Peptic ulcer; Indomethacin
... These results suggest that acute dosage of WAP is safe on the gastrointestinal tissue when compared with indomethacin. NSAIDs are highly associated with gastrointestinal distress causing peptic ulceration and bleeding (Al-Sayed and El-Naga, 2015). ...
The aim of the present study is to evaluate the anti-nociceptive and anti-inflammatory properties of an extract of a polyherbal mixture containing the leaves and roots of Plumbago zeylinica and fruits of Capsicum frutescens. Acute toxicity effect of WAP was evaluated in mice. The antinociceptive and anti-inflammatory activities of WAP (100–400 mg/kg) were investigated in hot plate, acetic acid-induced writhing, carrageenan-induced paw oedema and air pouch models. No death was recorded when WAP was administered at a dose of 2000 mg/kg. Oral treatment with WAP elicited inhibitory activity in hot plate test. Abdominal writhing was significantly reduced by WAP at 100, 200 and 400 mg/kg (54.5 ± 1.6, 20.0 ± 7.4, 38.4 ± 4.8) as compared with the control group (71.0 ± 2.6). Carrageenan-induced oedema formation was significantly (p < 0.05) reduced at WAP (100, 200, and 400 mg/kg) by 23.5, 27.3 and 31.4%, respectively, and by reference to indomethacin (10 mg/kg, 31.2%). WAP (200 and 400 mg/kg) significantly reduced exudate volume (37.2 and 44.1%), protein (42.0 and 54.1%), total leucocytes (59.1 and 60.2) and neutrophils count (57.3 and 58.0%) in the carrageenan-induced air pouch in rats. Similarly, WAP treated animals showed reduced nitrites and malondialdehyde levels and increased glutathione levels. Furthermore, WAP (400 mg/kg) nether affected locomotory activity nor induced gastric lesion in mice. The results of this study revealed that extract of a polyherbal mixture containing the leaves and roots of Plumbago zeylinica and fruits of Capsicum frutescens possesses anti-noiceptive and anti-inflammatory activity. © 2017, Ibadan Biomedical Communications Group. All rights reserved.
... Particularly, COX-2 is a major inflammatory mediator, which is predominantly expressed during inflammation. Regulating the expression of COX-2 in gastric tissue could mitigate gastric ulcer [47]. We found, HCl/EtOH treatment markedly increased the COX-2 protein expression in the gastric mucosal tissue whereas Camellia japonica pretreatment considerably blocked the COX-2 expression related to ranitidine indicating that improve the gastric healing of ulcerative damage. ...
Gastric ulcer is an important risk factor for human health globally. Camellia japonica (CJ) is a plant of which the fruits are used as traditional phytomedicine for inflammatory and immunomodulatory diseases; however, the underlying molecular mechanism has not been clarified. The present study aimed to investigate the immunopharmacological activities of Camellia japonica and validate its pharmacological targets. To evaluate the protective roles of Camellia japonica on LPS-induced inflammation in RAW 264.7 cells and HCl/EtOH-induced gastric ulcer in mice; we applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot analyses. We also determined the total phenolic and flavonoid content of Camellia japonica which might possess antioxidant and anti-inflammatory properties. We found the production of NO and ROS in RAW 246.7 cells were both suppressed by Camellia japonica. Moreover, Camellia japonica mitigated the HCl/EtOH-induced oxidative stress in gastric mucosa via the reduction of lipid peroxidation and elevation of NO production. Gastric mucosal damages were prominently improved by Camellia japonica, as confirmed by the histopathological evaluation. The gene expression of inflammatory cytokines and enzymes TNF-α, IL-6, IL-1β, iNOS, and COX-2 was notably downregulated by Camellia japonica. In addition, Camellia japonica markedly attenuated the MAPKs (ERK1/2, JNK, and p38) phosphorylation, COX-2 expression, and activation of transcription factor NF-κB and as well as degradation and phosphorylation of IκBα in gastric mucosa. Taken together, the intimated anti-inflammatory and gastroprotective mechanism of Camellia japonica is mediated by modulation of oxidative stress, inflammatory cytokines, and enzymes via suppression of MAPK/NF-κB signaling pathways.
... Moreover, we isolated a polysaccharide molecule (EP-1) with a molecular weight of 3 KDa from the mycelium of HE and showed that EP-1 prevented anti-gastric ulcer activity in both EtOHinduced gastric ulcer animal and cell models [3,4]. Since oxidative stress and inflammation play critical roles in pathogenesis of gastric ulcers caused by various stimuli, including Helicobacter pylori [22], studies of the antioxidant properties of EP-1 should be of value. Moreover, the antioxidant potential of polysaccharides has not been as extensively studied as has been done for low molecular weight ingredients, such as polyphenols [23]. ...
Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2–3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1. © 2017 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
... exerted strong analgesic, antioedematous, and anti-inflammatory effects [Rogerio et al., 2006]. Previous studies revealed that ellagitannins are strong inhibitors of proinflammatory mediators in different animal models [Al-Sayed and El-Naga, 2015]. Pomegranate ellagitannins showed anti-edematogenic activity on carrageenan-induced paw edema in rats and reduced the PGE 2 production through the inhibition of COX-2 expression [Lee et al., 2010]. ...
Preclinical Research
The anti‐inflammatory and analgesic activities of a polyphenol‐rich fraction (TMEF) obtained from Terminalia muelleri Benth. were measured. The analgesic activity of TMEF was tested using acetic acid‐induced writhing and hot plate models in mice. The anti‐inflammatory activity was assessed using carrageenan‐induced paw edema model by measuring PGE 2 , TNF‐α, IL‐1β, and IL‐6 plasma levels as well as the paw thickness. TMEF was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard (100 mg/kg) in all experiments. The group treated with 400 mg/kg of TMEF showed a greater inhibition in the number of writhes (by 63%) than the standard‐treated group (61%). Pretreatment with TMEF increased the analgesic effect in hot plate test in a dose‐dependent manner with a maximum effect after 120 min. TMEF pretreatment alos reduced the edema thickness by 48, 53, and 62% at the tested doses, respectively. TMEF administration inhibited the carrageenan‐induced elevations in PGE 2 (by 34, 43, and 47%), TNF‐α (18, 28, and 41%), IL‐1β (14, 22, and 29%), and IL‐6 (26, 31, and 46%). Four phenolic compounds were isolated from Terminalia muelleri for the first time. Drug Dev Res 78 : 146‐154, 2017. © 2017 Wiley Periodicals, Inc.
In a wide variety of soil types, Eucalyptus (family Myrtaceae) is an Australian native that has since been introduced to North and South Africa, Asia, and Southern Europe.
In the human body, the positive effects of phenolic compounds are increasingly observed through their presence in tissues and organs in their native form or in the form of metabolites or catabolites formed during digestion, microbial metabolism, and host biotransformation. The full extent of these effects is still unclear. The aim of this paper is to review the current knowledge of beneficial effects of native phenolic compounds or their metabolites and catabolites focusing on their role in the health of the digestive system, including disorders of the gastrointestinal and urinary tracts and liver. Studies are mostly connecting beneficial effects in the gastrointestinal and urinary tract to the whole food rich in phenolics, or to the amount of phenolic compounds/antioxidants in food. Indeed, the bioactivity of parent phenolic compounds should not be ignored due to their presence in the digestive tract, and the impact on the gut microbiota. However, the influence of their metabolites and catabolites might be more important for the liver and urinary tract. Distinguishing between the effects of parent phenolics vs metabolites and catabolites at the site of action are important for novel areas of food industry, nutrition and medicine.
Ethnopharmacological relevance
Peptic ulcer disease (PUD) ranks top among the most prominent gastrointestinal problems prevalent around the world. Long-term use of non-steroidal anti-inflammatory drugs, pathogenic infection by Helicobacter pylori, imbalances between gastrointestinal regulatory factors and pathological hyperacidity are major contributors towards the development of peptic ulcers. Although synthetic drugs of multiple pharmacological classes are abundantly available, inadequacy of such agents in ensuring complete recovery in not uncommon. Therefore, pharmacological explorations of herbal products including plant extracts and their respective isolated phytoconstituents, for potential gastroprotective and antiulcer properties, are regular practice among the scientific community. Moreover, the historical preferences of a significant share of world population towards herbal-based medication over modern synthetic drugs also contribute significantly to such endeavors.
Aim of the review
This review has endeavored to present ethnomedicinal and pharmacological prospects of a significant number of authenticated plant species in terms of their capacity to exert gastroprotection and antiulcer activities both in vitro and in vivo. The information delineated along the way was further subjected to critical analysis to ascertain the possible future prospects of such findings into designing plant-derived products in future for the treatment of peptic ulcer.
Materials and methods
Electronic version of prominent bibliographic databases, including Google Scholar, PubMed, Scopus, ScienceDirect, Wiley Online Library, SpringerLink, Web of Science, and MEDLINE were explored extensively for the identification and compilation of relevant information. The plant names and respective family names were verified through the Plant List (version 1.1) and World Flora Online 2021. All relevant chemical structures were verified through PubChem and SciFinder databases and illustrated with ChemDraw Ultra 12.0.
Results
A colossal number of 97 plant species categorized under 58 diverse plant families have been discussed in the review for their gastroprotective and antiulcer properties. In vivo illustrations of the pharmacological properties were achieved for almost all the species under consideration. 29 individual phytoconstituents from these sources were also characterized with similar pharmacological potentials. Majority of the plant extracts as well as their constituents were found to exert their gastroprotective effects through antioxidative pathway featuring both enzymatic and nonenzymatic mechanism. Moreover, active inhibition of acid secretion, upregulation of gastroprotective mediators and downregulation of pro-inflammatory cytokines, were also associated with a prominent number of plants or products thereof.
Conclusions
Comparative evaluations of the plant sources for their antiulcer activities, both as individual and as combination formulations, are necessary to be conducted in human subjects under properly regulated clinical conditions. Moreover, the efficacy and safety of such products should also be evaluated against those of the currently available treatment options. This will further facilitate in ascertaining their suitability and superiority, if any, in the treatment of peptic ulcer diseases. Implementation of these endeavors may eventually lead to development of more efficient treatment options in the future.
Abstract
Ethnopharmacological relevance
Peptic ulcer disease (PUD) ranks top among the most prominent gastrointestinal problems prevalent around the world. Long-term use of non-steroidal anti-inflammatory drugs, pathogenic infection by Helicobacter pylori, imbalances between gastrointestinal regulatory factors and pathological hyperacidity are major contributors towards the development of peptic ulcers. Although synthetic drugs of multiple pharmacological classes are abundantly available, inadequacy of such agents in ensuring complete recovery in not uncommon. Therefore, pharmacological explorations of herbal products including plant extracts and their respective isolated phytoconstituents, for potential gastroprotective and antiulcer properties, are regular practice among the scientific community. Moreover, the historical preferences of a significant share of world population towards herbal-based medication over modern synthetic drugs also contribute significantly to such endeavors.
Aim of the review
This review has endeavored to present ethnomedicinal and pharmacological prospects of a significant number of authenticated plant species in terms of their capacity to exert gastroprotection and antiulcer activities both in vitro and in vivo. The information delineated along the way was further subjected to critical analysis to ascertain the possible future prospects of such findings into designing plant-derived products in future for the treatment of peptic ulcer.
Materials and methods
Electronic version of prominent bibliographic databases, including Google Scholar, PubMed, Scopus, ScienceDirect, Wiley Online Library, SpringerLink, Web of Science, and MEDLINE were explored extensively for the identification and compilation of relevant information. The plant names and respective family names were verified through the Plant List (version 1.1) and World Flora Online 2021. All relevant chemical structures were verified through PubChem and SciFinder databases and illustrated with ChemDraw Ultra 12.0.
Results
A colossal number of 97 plant species categorized under 58 diverse plant families have been discussed in the review for their gastroprotective and antiulcer properties. In vivo illustrations of the pharmacological properties were achieved for almost all the species under consideration. 29 individual phytoconstituents from these sources were also characterized with similar pharmacological potentials. Majority of the plant extracts as well as their constituents were found to exert their gastroprotective effects through antioxidative pathway featuring both enzymatic and nonenzymatic mechanism. Moreover, active inhibition of acid secretion, upregulation of gastroprotective mediators and downregulation of pro-inflammatory cytokines, were also associated with a prominent number of plants or products thereof.
Conclusions
Comparative evaluations of the plant sources for their antiulcer activities, both as individual and as combination formulations, are necessary to be conducted in human subjects under properly regulated clinical conditions. Moreover, the efficacy and safety of such products should also be evaluated against those of the currently available treatment options. This will further facilitate in ascertaining their suitability and superiority, if any, in the treatment of peptic ulcer diseases. Implementation of these endeavors may eventually lead to development of more efficient treatment options in the future.
Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1′''-6′')-(4′'- O -acetyl)-β -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3′-O-β-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1′''-6′')-(4′'- O -acetyl)- β –Dgalactoside (4), quercetin-3- O—β -D-galactoside (5), 7-hydroxy maltol-3-O-β-D-glucoside (6), maltol-3- O-β -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.
Graphic abstract
Ellagitannins have a marked antioxidant effect and can prevent liver injury induced by free radicals. An undescribed ellagitannin named styphelioidin was isolated from Melaleuca styphelioides Sm. The structure of styphelioidin was elucidated by using various spectroscopic methods. The hepatoprotective activity of styphelioidin (25, 50, and 100 μM) was tested using the CCl4-challenged HepG2 cell model by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HepG2 cells treated with styphelioidin for 1 h followed by 40 mM CCl4. Glutathione (GSH), superoxide dismutase activity (SOD) and lipid peroxidation (MDA) were evaluated to determine the mechanisms of the hepatoprotective activity. Styphelioidin significantly reduced the levels of ALT, AST, and MDA at all tested concentrations. Moreover, it conferred a marked increase in the GSH levels and the SOD activity compared to the CCl4-treated groups. Styphelioidin also exerted DPPH· radical-scavenging effects with an IC50 value of 3.67 μM. Results indicated the hepatoprotective therapeutic potential of styphelioidin comparable to silymarin. Moreover, anti-inflammatory activity was assessed and styphelioidin inhibited fMLF/CB-induced elastase release in human neutrophils with IC50 2.51 μM. Cell-free experiments with human neutrophil elastase indicated a direct enzymatic inhibitory effect of styphelioidin on the enzyme activity (IC50 2.58 μM). The potential of styphelioidin to interact with human neutrophil elastase binding sites was further confirmed by molecular docking of styphelioidin into human neutrophil elastase crystal structure using AutoDock 4.2. Styphelioidin represents a potent hepatoprotective and antioxidant agent with effects on ALT, AST, MDA, GSH, and SOD comparable to silymarin. The beneficial anti-elastase properties hold the potential for drug development against elastase-related inflammatory diseases. This study highlights a promising natural hepatoprotective and anti-inflammatory candidate derived from M. styphelioides.
Pachira glabra is a medium sized tree that is famous for its delicious edible seeds and leaves. Phytochemical investigation of Pachira glabra leaf alcohol extract led to the isolation of a new γ-pyrone glycoside; 7-hydroxy maltol-3-O-β-D-glucoside (HMGlu). In vivo assessment of gastro-protective activity of HMGlu demonstrated superior gastro-protection at dose of 100 mg/kg approaching that triggered by standard reference omeprazole drug (evidenced by morphological and histopathological examination. This was further confirmed by immunohistochemical staining where pretreatment with HMGlu (100 mg/kg) markedly reduced NFкB, COX-2 and BAX positively-stained. Thus, it can be concluded that 7-hydroxy maltol-3-O-β-D-glucoside can offer a new pharmaceutically active agent with promising gastro-protective activity of natural origin.
Ethnopharmacological relevance:
Members of the genus Erythrina have been traditionally used in the treatment of various ailments such as inflammation and gastrointestinal disorders. Erythrina speciosa (Fabaceae) is a spiny, deciduous shrub or small tree native to Southern America in Brazil. It is cultivated in Africa and Asia. The traditional usage of E. speciosa indicated its antibacterial, analgesic, and anti-inflammatory activities.
Aim of the study:
Evaluation of the phytochemical constituents, gastroprotective effects and possible mechanism of action of the ethyl acetate fraction obtained from the methanol extract of E. speciosa leaves (ESLE).
Materials and methods:
Chemical characterization of ESLE was done using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The gastroprotective activity of ESLE was evaluated using ethanol-induced gastric-ulcer model in rats. Rats were pre-treated with ESLE 25, 50 and 100 mg/kg 1 h before the administration of absolute ethanol. Histological analysis, mucin content, and total acidity were evaluated. The possible mechanism of action of ESLE was studied through the examination of oxidative stress and inflammatory markers, PGE2, and NF-κB, iNOS, COX-2, and HSP-70 immunoexpression. In vitro, anti-Helicobacter pylori activity of ESLE was also studied using micro-well dilution method.
Results:
Fourteen compounds were tentatively identified including alkaloids, flavonoids, and saponins. ESLE exerted a powerful gastroprotective effect. The pre-treatment with ESLE at different doses resulted in a significant reduction in gastric lesions and significant elevation in the mucin production. These effects could be partially mediated by the potent anti-inflammatory activity of ESLE as evidenced by the significant reduction in the immunoexpression of NF-κB, COX-2, iNOS and the reduction in the pro-inflammatory marker, TNF-α. ESLE counteracted the ethanol-induced oxidative stress by increasing the levels of depleted GSH and catalase as well as significantly attenuating the ethanol-induced lipid peroxidation tissue levels. In addition, ESLE exhibited in vitro antibacterial activity against H. pylori.
Conclusions:
The chemical constituents of ESLE strongly support its potent gastroprotective effect suggesting its future potential application in the management of gastric ulcer by eliminating its symptoms and causes including H. pylori.
Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3–9) as the extract’s major components. The in vivo antiulcer study at three different doses (50, 100, and 200 mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20 mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regard to reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.
Graphic abstract
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Pain is among the major concerns of healthcare authorities across the world. It is complicated to diagnose, manage and treat. Current western treatments are successful to some extent in relieving pain; they provide minimum improvements in terms of physical and emotional functioning and are often accompanied by side effects. Finding new solutions in pain management has thus become a priority. Natural products have always been a huge source of new active principles; traditional medicine is thus a key to innovation. In Mali, traditional remedies are more popular than pharmaceutical drugs but this knowledge, verbally transferred from generation to generation is at risk as younger generations are not taking over. Thus, this study was designed to identify plants that are used traditionally in the South of Mali for the treatment of painful conditions. Data was collected by means of semi-structured face-to-face interviews with traditional healers (N = 108) in the regions of Bamako, Sikasso and Dioïla. Two quantitative ethnopharmacological indexes were calculated: Relative Frequency of Citation (RFC) and Fidelity Level (FL) when RFC > 0.10. A total of 66 plant species distributed across 29 families were recorded during this two-month survey. Stomach aches and external pains were the most cited pain conditions followed by body pains and pain due to diseases such as diabetes and sickle cell disease. Cassia sieberiana DC. (RFC = 0,22), Zanthoxylum zanthoxyloides (Lam.) Zepren. & Timler (0,13), Pericopsis laxiflora (Benth.) Meeuwen (0,11), Flueggea virosa (Roxb. ex Willd) Royle (0,08) and Sarcocephalus latifolius (Sm.) E.A.Bruce (0,08) were the most cited plants. This ethnopharmacological survey provides preliminary data for the discovery of new analgesic molecules.
The effect of omeprazole, a commonly used drug belongs to proton–‐pump inhibitor class, on human sperm function is still undetermined. Here, we hypothesised that addition of omeprazole to the ejaculated human semen may affect sperm parameters, and hence sperm function. Therefore, we assessed the in vitro effect of omeprazole on human sperm motility, viability and DNA integrity. Sixty‐six normozoospermic semen samples were collected randomly from men who attended the andrology laboratory at King Abdullah University Hospital. Sperm motility, viability and DNA breaks were assessed in the presence (1‐hr incubation at 37°C) of omeprazole at 5, 10, 20 and 50 µM compared to control (0 µM). None of the examined sperm parameters, at any tested omeprazole concentration, showed significant difference (p > 0.05) compared with the control. In conclusion, omeprazole at 5, 10, 20 and 50 µM does not alter human sperm motility, viability or DNA integrity in vitro.
The gastroprotective effect of Ocimum basilicum L. (Basil) hexane extract (OBHE) in aspirin-induced gastric ulcer in mice and its ameliorative effect on behavioral alterations was determined. Pretreatment with OBHE (100 or 200 mg/kg) or misoprostol (50 µg/kg) alleviated the aspirin-induced oxidative stress by significantly decreasing (p ˂ 0.001) gastric MDA (by 49, 51 and 52%), NO (21, 28 and 29%) and H2O2 (24, 42 and 45%), as well as by markedly increasing gastric GSH (41, 61 and 70%), GSH-Px (21, 32 and 34 %), GST (33, 63 and 70%), GR (90, 99 and 112 %) and CAT (167, 211 and 267%), respectively, as compared to the aspirin-ulcerated group. A significant decrease (p ˂ 0.001) in proinflammatory mediator TNF-α (21, 53 and 53%) and IL-6 (29, 30 and 31%), along with a marked increase in PGE-2 levels (22, 135 and 200%) and IL-4 (64, 81 and 104%) were evident in the groups treated with OBHE or misoprostol, respectively. Meanwhile, OBHE and misoprostol induced a significant decrease (p ˂ 0.001) in the freezing time (53, 56 and 64%), and the grooming time (by 25, 43 and 44%), respectively, as compared to aspirin group. The higher dose of OBHE and misoprostol produced 76% and 79% gastroprotective effect against aspirin. This study provides evidence that OBHE confers anxiolytic, antioxidant and anti-inflammatory prophylactic effects in aspirin-induced gastric ulcer. GC/MS was used for characterization of OBHE components. Based on the findings of this study, basil may be used as a nutritional supplement or therapeutic drug to protect against aspirin-induced gastric ulcers, a common problem resulting from the use of aspirin.
It is believed that many degenerative diseases are due to oxidative stress. In view of the limited drugs available for treating degenerative diseases, natural products represent a promising therapeutic strategy in the search for new and effective candidates for treating degenerative diseases. This review focuses on the genus Spondias which is widely used in traditional medicine for the treatment of many diseases. Spondias is a genus of flowering plants belonging to the cashew family (Anacardiaceae). This genus comprises 18 species distributed across tropical regions in the world. A variety of bioactive phytochemical constituents were isolated from different plants belonging to the genus Spondias . Diverse pharmacological activities were reported for the genus Spondias including cytotoxic, antioxidant, ulcer protective, hepatoprotective, anti-inflammatory, antiarthritic, and antidementia effects. These attributes indicate their potential to treat various degenerative diseases. The aim of this review is to draw attention to the unexplored potential of phytochemicals obtained from Spondias species, thereby contributing to the development of new therapeutic alternatives that may improve the health of people suffering from degenerative diseases and other health problems.
Pharmacological relevance:
Artemisia argyi, a kind of ethnic drug, has a long-term use on gastric diseases and syndromes.
Aim of the study:
The aim of the study is to validate the traditional uses of A. argyi scientifically and to discover more efficient nature derived gastro-protective ethnomedicine and further elucidate the possible mechanisms.
Materials and methods:
Sixty rats were randomly divided into control, model (ethanol-induced), reference (omeprazole-treated) and A. argyi extract (AT) (0.3, 0.1, 0.033g/mL) treated groups, respectively. The levels of biochemical indexes in tissues and serum and the activities of pepsin in gastric contents were measured after the sacrifice of rats. Moreover, the anti-inflammatory effects in LPS-induced RAW 264.7 cells of the isolated compounds were determined.
Results:
The studies indicated that A. argyi extract could exert strong protective effects on gastric mucosa in ethanol-induced rat model by regulating the levels of inflammatory factors, superoxide dismutase, and malonaldehyde, which were superior to those of positive control at 0.3g/mL. The isolated flavonoids could down-regulate the levels of pro-inflammatory cytokines on LPS-induced RAW 264.7 macrophage cells and eliminate free radicals in the anti-oxidative tests. The effects of eupatilin and jaceosidin, which were substituted by additional methoxy groups, were predominant, indicting the importance of methoxy to the activities.
Conclusion:
The results confirmed that A. argyi can protect ethanol-induced rats from gastric mucosal injury through inhibiting inflammatory responses and ameliorating oxidative stress. A. argyi is suitable for people with gastric mucosal injuries or unhealthy dietary habits as a necessary dietary supplement, which will promote the planting and application of A. argyi in both agriculture and food industry.
Many studies quantify total phenolics or total tannins, but understanding the ecological role of poly-phenolic secondary metabolites requires at least an understanding of the diversity of phenolic groups present. We used UPLC-MS/MS to measure concentrations of different polyphenol groups-including the four most common tannin groups, the three most common flavonoid groups, and quinic acid derivatives-in foliage from 628 eucalypts from the genera Eucalyptus, Angophora and Corymbia. We also tested for phylogenetic signal in each of the phenolic groups. Many eucalypts contained high concentrations of polyphenols, particularly ellagitannins, which have been relatively poorly studied, but may possess strong oxidative activity. Because the biosynthetic pathways of many phenolic compounds share either precursors or enzymes, we found negative correlations between the concentrations of several of the constituents that we measured, including proanthocyanidins (PAs) and hydrolysable tannins (HTs), HTs and flavonol derivatives, and HTs and quinic acid derivatives. We observed moderate phylogenetic signal in all polyphenol constituents, apart from the concentration of the prodelphinidin subunit of PAs and the mean degree of polymerisation of PAs. These two traits, which have previously been shown to be important in determining plants' protein precipitation capacity, may have evolved under selection, perhaps in response to climate or herbivore pressure. Hence, the signature of evolutionary history appears to have been erased for these traits. This study is an important step in moving away from analysing " totals " to a better understanding of how phylogenetic effects influence phenolic composition, and how this in turn influences ecological processes.
Licania platypus, locally known as " Traditionally, it has been used different anatomical parts in Central America for a variety of health problems, especially gastrointestinal problems. Aim: To investigate the possible gastric antiulcer act Methods: Gastric lesions were induced by ethanol and indomethacin models. Also the extract was evaluated in modified Shay rat model. Licania platypus were measured. Besides, other parameters were analyzed in pylorus Results: Oral administration of a unique dose of ethanol extract (500 mg/kg) significantly reduced the area of gastric lesions (p < 0.05) on ethanol and indomethacin significant increase of the gastric mucus secretion in modified Shay model (p < 0.05). Conclusion: Licania platypus ethanol extract exerted a gastroprotective induction models. This work provides the first evidence that species of activity and permits further studies to elucidate a specific mechanism
In addition to its advantages (technological progress, high-performance medical treatment, multiple information sources, new communication systems), the 21st century brings many disadvantages, such as: professional stress due to the uncertainty of the future and to the increasingly higher professional performance indicators, the quality of interpersonal relationships, an imbalance between professional and personal life, a lack of interest in self-knowledge. Besides all these stress factors, certain drugs, inadequate nutrition both in terms of quantity and quality, a small number of meals eaten per day, a late last meal, as well as late bedtime cause an increase of gastric secretion. Depending on the psychosomatic profile of patients, these can be divided into two main categories: patients who accept drug therapy and patients who prefer alternative therapies. This review aims to present all types of alternative therapies, for which preclinical studies are available. © 2017, Romanian Society for Pharmaceutical Sciences. All Rights reserved.
Ethnopharmacological relevance:
Taraxacum coreanum Nakai has been traditionally used for treating inflammatory diseases including gastrointestinal diseases.
Aim of the study:
We studied whether water extracts of Taraxacum coreanum Nakai (TCN) had a protective effect on acute and chronic gastritis induced by ethanol/HCl in an animal model of gastritis and its mechanism was also explored.
Materials and methods:
In the acute study, rats were orally administered 0.15g/mL dextrin (normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN (TCN-H), or 0.01g/ml omeprazole (orally; positive-control), followed by oral administration of 1ml of 60% ethanol plus 150mM HCl (inducer). In the chronic study, rats were administered 10% diluted inducer in drinking water, and 0.6% dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4 weeks. Acid content, gastric structure, oxidative stress, and markers of inflammation in the stomach tissue were measured at the end of experiment.
Results:
Acute and chronic ethanol/HCl administration caused the inner layer of the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced these symptoms more effectively than did the omeprazole positive-control. Acid production and total acidity in the stomach increased in the control group, which was markedly suppressed by omeprazole. TCN also reduced the acid production and acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed that in the inner layer of the stomach, cellular structure was disrupted, with an increased nuclear size and thickness, disarrangement, and decreased mucin in the control group. TCN prevented the cellular disruption in the inner layer, and TCN-H was more effective than the positive-control. This was associated with oxidative stress and inflammation. TCN dose-dependently reduced the infiltration of mast cells and TNF-α expression in the inner layer of the stomach, and decreased lipid peroxides by increasing superoxide dismutase and glutathione peroxidase expression.
Conclusions:
TCN-H acutely and chronically protected against gastritis and gastric ulcer by reducing oxidative stress and inflammation, not by completely suppressing gastric acid production.
Context:
Schistosomiasis is a parasitic disease that results in severe organ damage. Snail control is the best measure to control schistosomiasis. Plant-derived molluscicides have gained increasing attention for the control of schistosomiasis because they have low toxicity towards non-target organisms. Tannins are particularly suitable for snail control because they are less toxic than saponins to non-target organisms.
Objective:
To identify the most toxic components of two plants belonging to the family Myrtaceae, namely Eucalyptus globulus Labill. and Melaleuca styphelioides Sm against the different developmental stages of Schistosoma mansoni and its snail host.
Materials and methods:
The 80% MeOH leaf extracts of the tested plants and their isolated compounds were screened for their molluscicidal activity (expressed as LC50 and LC90 after 24 h exposure) against the snail Biomphalaria alexandrina. The anti-schistosomal activity of the tested samples was determined at 20 ppm (after 1 or 2 h exposure) against the different developmental stages of S. mansoni, including the miracidia, cercariae and worms. Biochemical parameters were measured to determine the toxicity mechanisms of the treated snails. The structures of the isolated compounds were elucidated based on NMR, UV and HRESI-MS/MS data.
Results:
Potent molluscicidal activity was observed for the ellagitannin dimer eucalbanin B (12), with an LC50 value of 55 ppm. Treatment of the snails with the LC25 of eucalbanin B (30.8 ppm) resulted in a significant decrease in the protein level by 22.7% and 25.8% in the snail tissues and hemolymph, respectively. The decreased protein content was attributed to destruction of the snail tissue and impairment in protein synthesis under stress conditions of intoxication with eucalbanin B. Alterations in the activities of the transaminases and phosphatases in the treated snails indicated destruction and intoxication of the snail tissues. A significant increase in the levels of the transaminases alanine aminotransferase (ALT) (57.8%) and aspartate aminotransferase (AST) (113.2%) in the snail hemolymph and a significant decrease in their tissue levels to 7.4 and 48.6%, respectively, were attributed to their release from the damaged tissue into the hemolymph. Alkaline phosphatase (ALP) was significantly increased by 38.5 and 181.4% in the hemolymph and tissues, respectively. Acid phosphatase (ACP) was also significantly increased by 48.4 and 21.2% in the hemolymph and tissues, respectively. The 80% MeOH extract of E. globulus together with mallophenol B (3), 2,2,8-trimethyl-6-formyl-chrom-3-ene-7-O-β-d-glucopyranoside (5) and benzyl alcohol 7-O-(3',4',6'-tri-O-galloyl)-β-d-glucopyranoside (10) exhibited miracidicidal activity with almost 100% toxicity at 20 ppm for the three compounds and 80% toxicity for the extract. Moreover, E. globulus extract showed cercaricidal and schistosomicidal activity with 100 and 40% mortality, respectively.
Conclusion:
E. globulus is a potential source for biocidal compounds against S. mansoni and its snail host. This is the first study to test the biocidal activity of the isolated compounds.
Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.
Ellagitannins have shown anti-inflammatory and anti-Helicobacter pylori properties; however, their anti-inflammatory activity at gastric level was not previously investigated. The aim of this research was to evaluate the effects of ellagitannins from Rubus berries on gastric inflammation. Ellagitannin enriched extracts (ETs) were prepared from Rubus fruticosus L. (blackberry) and Rubus idaeus L. (raspberry). The anti-inflammatory activity was tested on gastric cell line AGS stimulated by TNF-α and IL-1β for evaluating the effect on NF-kB driven transcription, nuclear translocation and IL-8 secretion. In vivo the protective effect of ellagitannins was evaluated in a rat model of ethanol-induced gastric lesions. Rats were treated orally for ten days with 20 mg/kg/day of ETs, and ethanol was given one hour before the sacrifice. Gastric mucosa was isolated and used for the determination of IL-8 release, NF-kB nuclear translocation, Trolox equivalents, superoxide dismutase and catalase activities. In vitro, ETs inhibited TNF-α induced NF-kB driven transcription (IC50: 0.67-1.73 µg/mL) and reduced TNF-α-induced NF-kB nuclear translocation (57%-67% at 2 µg/mL). ETs inhibited IL-8 secretion induced by TNF-α and IL-1β at low concentrations (IC50 range of 0.7-4 µg/mL). Sanguiin H-6 and lambertianin C, the major ETs present in the extracts, were found to be responsible, at least in part, for the effect of the mixtures. ETs of blackberry and raspberry decreased Ulcer Index by 88% and 75% respectively and protected from the ethanol induced oxidative stress in rats. CINC-1 (the rat homologue of IL-8) secretion in the gastric mucosa was reduced in the animals receiving blackberry and raspberry ETs. The effect of ETs on CINC-1 was associated to a decrease of NF-κB nuclear translocation in ETs treated animals. The results of the present study report for the first time the preventing effect of ETs in gastric inflammation and support for their use in dietary regimens against peptic ulcer.
To investigate the effect of moxibustion-acupoint treatment with acupoints of Zusanli (ST 36) and Zhongwan (RN 12) on cell apoptosis and the expressions of heat shock protein (HSP) 60, HSP70 and second mitochondrial activator of caspase (Smac) in rat models of acute gastric mucosal lesion (AGML), and explore the mechanisms underlying protection of gastric mucosal lesion.
Twenty-four Sprague Dawley rats were divided into 3 groups, blank controlled group (group A), controlled-point group (group B) and acupoint group (group C), 8 for each. After 8-day moxibustion treatment in group B and C, gastric lavage of anhydrous ethanol was used to created AGML in all three groups. The Guth method was employed to measure the ulcer index (UI) of gastric mucosal lesion and immunohistochemistry used to measure apoptosis with apoptosis index (AI) and examine the expressions of HSP60, HSP70 and Smac.
Compared with group A, the expressions of UI, AI, Smac and HSP60 were markedly elevated in group B (P < 0.05 or P < 0.01). However the expression of HSP70 showed no obvious change (P > 0.05); the expressions of UI, HSP60 and HSP70 were markedly elevated in group C (P < 0.01) while those of AI and Smac became obviously suppressed (P < 0.01). Compared with group B, the expressions of UI, AI and Smac decreased significantly in group C (P < 0.01) while those of HSP60 and HSP70 increased markedly (P < 0.01), and the expressions of HSP60 and HSP70 were considerably up-regulated (P < 0.01).
The moxibustion treatment could alleviate the gastric mucosal lesion caused by anhydrous ethanol, induce the over-expressions of HSP60 and HSP70, and down-regulate the expression of Smac, which could suppress cell apoptosis.
Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of Ehrlich ascites carcinoma and Sarcoma 180. The results showed that ethyl acetate and aqueous extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%, respectively). The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which has shown significant in vitro and in vivo anticancer potential.
Cymbopogon citratus and Eucalyptus citriodora are widely used herbs/plants as a source of ethnomedicines in tropical regions of the world. In this work, we studied the anti-inflammatory and gastroprotective effects of C. citratus and E. citriodora essential oils on formol-induced edema, and acetic acid induced abdominal cramps in Wistar rats. To fully understand the chemically induced anti-inflammatory properties of these plants, we first analyzed the chemical composition of the essential oils. A total of 16 chemical constituents accounting for 93.69 % of the oil, were identified in C. citratus among which, Geranial (27.04 %), neral (19.93 %) and myrcene (27.04 %) were the major constituents. For E. citriodora, 19 compounds representing 97.2 % of the extracted oil were identified. The dominant compound of E. citriodora essential oil was citronellal (83.50 %). In vivo analysis and histological assay showed that the two essential oils displayed significant dose dependent edema inhibition effect over time. They displayed strong analgesic and antipyretic properties similar to that induced by 50 mg/kg of acetylsalicylate of lysine. However, the E. citriodora essential oil was more effective than that of C. citratus. We identified significant numbers of aldehyde molecules in both essential oils mediating antioxidant activity that may contribute to the anti-inflammatory effects observed on the rats. Altogether, this work demonstrates the anti-inflammatory property of C. citratus and E. citriodora suggesting their potential role as adjuvant therapeutic alternatives in dealing with inflammatory-related diseases.
This review of the current literature aims to study correlations between the chemical structure and gastric anti-ulcer activity of tannins. Tannins are used in medicine primarily because of their astringent properties. These properties are due to the fact that tannins react with the tissue proteins with which they come into contact. In gastric ulcers, this tannin-protein complex layer protects the stomach by promoting greater resistance to chemical and mechanical injury or irritation. Moreover, in several experimental models of gastric ulcer, tannins have been shown to present antioxidant activity, promote tissue repair, exhibit anti Helicobacter pylori effects, and they are involved in gastrointestinal tract anti-inflammatory processes. The presence of tannins explains the anti-ulcer effects of many natural products.
The antioxidant activities and total phenolics of 28 plant products, including sunflower seeds, flaxseeds, wheat germ, buckwheat, and several fruits, vegetables, and medicinal plants were determined. The total phenolic content, determined according to the Folin−Ciocalteu method, varied from 169 to 10548 mg/100 g of dry product. Antioxidant activity of methanolic extract evaluated according to the β-carotene bleaching method expressed as AOX (Δ log A470/min), AA (percent inhibition relative to control), ORR (oxidation rate ratio), and AAC (antioxidant activity coefficient) ranged from 0.05, 53.7, 0.009, and 51.7 to 0.26, 99.1, 0.46, and 969.3, respectively. The correlation coefficient between total phenolics and antioxidative activities was statistically significant. Keywords: Antioxidant activity; phenolics; medicinal plants; oilseeds; buckwheat; vegetables; fruits; wheat products
Background and aim:
Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa.
Methods/principal findings:
Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found.
Conclusions:
Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.
Peptic ulcer is the most common gastrointestinal tract (GIT) disorder in clinical practice, which affects approximately 5-10% of the people during their life. The use of herbal drugs for the prevention and treatment of various diseases is constantly developing throughout the world. This is particularly true with regard to phenolic compounds that probably constitute the largest group of plants secondary metabolites. Phenolic compounds have attracted special attention due to their health-promoting characteristics. In the past ten years a large number of the studies have been carried out on the effects of phenolic compounds on human health. Many studies have been carried out that strongly support the contribution of polyphenols to the prevention of cardiovascular diseases, cancer, osteoporosis, neurodegenerative diseases, and diabetes mellitus, and suggest a role in the prevention of peptic ulcer. Polyphenols display a number of pharmacological properties in the GIT area, acting as antisecretory, cytoprotective, and antioxidant agents. The antioxidant properties of phenolic compounds have been widely studied, but it has become clear that their mechanisms of action go beyond the modulation of oxidative stress. Various polyphenolic compounds have been reported for their anti-ulcerogenic activity with a good level of gastric protection. Besides their action as gastroprotective, these phenolic compounds can be an alternative for the treatment of gastric ulcers. Therefore, considering the important role of polyphenolic compounds in the prevention or reduction of gastric lesions induced by different ulcerogenic agents, in this review, we have summarized the literature on some potent antiulcer plants, such as, Oroxylum indicum, Zingiber officinale, Olea europaea L., Foeniculum vulgare, Alchornea glandulosa, Tephrosia purpurea, and so on, containing phenolic compounds, namely, baicalein, cinnamic acid, oleuropein, rutin, quercetin, and tephrosin, respectively, as active constituents.
Fumaria species (Fumariaceae) have been recorded to be used traditionally against liver-related disorders in many countries including Turkey. Oxidative stress is also known to be strongly associated with hepatic problems. Consequently, in the current study, the ethanol extracts of four Fumaria species; F. cilicica Hausskn., F. densiflora DC., F. kralikii Jordan and F. parviflora Lam. growing in Turkey were initially screened for their in vitro antioxidant activities by three methods; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test, Fe(+2)-ferrozine test system for metal chelating test and ferric-ion reducing antioxidant power (FRAP) at 250, 500 and 1000 μg/ml concentrations. Then, each of the ethanol extracts was fractionated into petroleum ether, chloroform, ethyl acetate and methanol fractions and their antioxidant activities were estimated by DPPH radical scavenging and xanthine oxidase inhibition tests at 1000 μg/ml. In both tests, the chloroform and ethyl acetate fractions of F. cilicica were found to be the most active and were further investigated in in vivo hepatoprotective activity experiment against toxicity induced by CCl(4). Total phenol and flavonoid quantities of the ethanol extracts were determined spectrophotometrically using Folin-Ciocalteau's and AlCl(3) reagents, respectively. Our data revealed that the chloroform and ethyl acetate fractions of F. cilicica did not have hepatoprotective effect and the ethanol extracts exerted low antioxidant activity. Although protective effect of some Fumaria species in hepatic diseases was shown in several previous studies, this record seems to be not pertinent for F. cilicica.
Calcitonin gene-related peptide (CGRP) is a polypeptide produced by alternative processing of calcitonin gene transcripts and is endowed with important systemic physiological effects. The recent characterization of its receptor and the discovery of stable antagonists has addressed them in the indication migraine. Beside this, several studies have been focused on role of CGRP at gastric level. CGRP is considered a marker of afferent fibers in the upper gastrointestinal tract being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor potential vanilloid of type-1. The exogenous administration of the peptide was able to afford protection against experimental ulcers induced by an increase in gastric secretion. The use of CGRP knockout mice has let to characterize the endogenous role of CGRP showing that the local release of this neuropeptide protects from ethanol injury and favours ulcer healing. Decreased levels of gastric CGRP-like immunoreactivity (li) were observed during acetic acid-, cysteamine-, concentrated ethanol- or water immersion stress-ulcers. Restoration of CGRP-li was found in animals bearing ulcers in healing status and delayed healing in mice knockout to CGRP. CGRP was able to release somatostatin from gastric D cells but its main effects on the stomach homeostasis rely on local vasodilator action during increased acid-back diffusion.
Except in rare cases, the stomach can withstand exposure to highly concentrated hydrochloric acid, refluxed bile salts, alcohol, and foodstuffs with a wide range of temperatures and osmolarity. This is attributed to a number of physiological responses by the mucosal lining to potentially harmful luminal agents, and to an ability to rapidly repair damage when it does occur. Since the discovery in 1971 that prostaglandin synthesis could be blocked by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), there has been great interest in the contribution of prostaglandins to gastric mucosal defense. Prostaglandins modulate virtually every aspect of mucosal defense, and the importance of this contribution is evident by the increased susceptibility of the stomach to injury following ingestion of an NSAID. With chronic ingestion of these drugs, the development of ulcers in the stomach is a significant clinical concern. Research over the past two decades has helped to identify some of the key events triggered by NSAIDs that contribute to ulcer formation and/or impair ulcer healing. Recent research has also highlighted the fact that the protective functions of prostaglandins in the stomach can be carried out by other mediators, in particular the gaseous mediators nitric oxide and hydrogen sulfide. Better understanding of the mechanisms through which the stomach is able to resist injury in the presence of luminal irritants is helping to drive the development of safer anti-inflammatory drugs, and therapies to accelerate and improve the quality of ulcer healing.
The structures of three hydrolyzable tannins, i.e., grandinin (3) (isolated from various species of Myrtaceae, Fagaceae and Lythraceae), pterocarinin A (4) (from Pterocarya steroptera C.DC. and Eucalyptus viminalis LABILL.) and pterocarinin B (6) (from P. stenoptera), have been established on the basis of chemical and spectroscopic evidence as novel C-glycosidic ellagitannins in which a C5-polyalcohol unit with lyxose-type configuration is linked through a carbon-carbon bond to the C-1 position of the C-glycosyl moiety. Successful biomimetic synthesis of 3 and 4 suggests that the C5-polyalcohol unit is biosynthetically derived from L-ascorbic acid.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
Six new complex tannins, guajavins A (5) and B (1), psidinins A (9), B (11) and C (13), and psiguavin (15), together with a variety of condensed, hydrolyzable and complex tannins, have been isolated from the bark of Psidium guajava L. (Myrtaceae). On the basis of chemical and spectroscopic evidence, the structures of guajavins and psidinins were established to consist of a (+)-gallocatechin unit and a hydrolyzable tannin moiety linked C-glycosidically, while psiguavin was found to be a novel metabolite probably derived from eugenigrandin A (7) through successive oxidation, benzylic acid-type rearrangement, decarboxylation and oxidative coupling of the gallocatechin B-ring and one of the aromatic rings in the hydrolyzable tannin moiety.
Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats. Gastric ulcers were induced by intragastric administration of 75% ethanol. Ghrelin alone or in combination with cyclooxygenase inhibitors was administered twice, 1 and 13 hours after ethanol application. Cyclooxygenase-1 (COX-1) inhibitor (SC-560, 10 mg/kg/dose) or COX-2 inhibitor (celecoxib, 10 mg/kg/dose) were given 30 min prior to ghrelin. Twelve or 24 hours after administration of ethanol, rats were anesthetized and experiments were terminated. The study revealed that administration of ethanol induced gastric ulcers in all animals and this effect was accompanied by the reduction in gastric blood flow and mucosal DNA synthesis. Moreover induction of gastric ulcer by ethanol significantly increased mucosal expression of mRNA for COX-2, IL-1β and TNF-α. Treatment with ghrelin significantly accelerated gastric ulcer healing. Therapeutic effect of ghrelin was associated with significant reversion of the ulcer-evoked decrease in mucosal blood flow and DNA synthesis. Ghrelin administration also caused the reduction in mucosal expression of mRNA for IL-1β and TNF-α. Addition of SC-560 slightly reduced the therapeutic effect of ghrelin in the healing of ethanol-induced ulcer and the ulcer area in rats treated SC-560 plus ghrelin was significantly smaller than that observed in rats treated with saline or SC-560 alone. Pretreatment with celecoxib, a COX-2 inhibitor, abolished therapeutic effect of ghrelin. We concluded that treatment with ghrelin increases healing rate of gastric ulcers evoked by ethanol and this effect is related to improvement in mucosal blood flow, an increase in mucosal cell proliferation, and reduction in mucosal expression of proinflammatory cytokines. Ghrelin is able to reverse a deleterious effect of COX-1 inhibitor on healing of ethanol-induced gastric ulcers. Activity of COX-2 is necessary for the therapeutic effect of ghrelin in healing of ethanol-induced gastric ulcers.
The prevalence of gastric ulcers is high in cholestatic patients, but the exact mechanism of this increased frequency remains uncertain. It has been shown that pioglitazone accelerates the healing of pre-existing gastric ulcers. The present study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation of common bile duct and sham-operated rats served as control. Different groups of sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg) for 7 days. On the day eight rats were killed after oral ethanol administration and the area of gastric lesions was measured. The serums of rats were also collected to determine serum levels of tumour necrosis factor alpha (TNF-α), IL-1β and bilirubin. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than sham-operated ones. Pretreatment with pioglitazone dose-dependently attenuated gastric lesions induced by ethanol in both sham and cholestatic rats, but this effect was more prominent in cholestatic ones. The effect of pioglitazone was associated with a significant fall in serum levels of TNF-α in cholestatic rats. L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone-induced gastroprotective effect in cholestatic rats, while aminoguanidine, a selective inducible NOS inhibitor, potentiated pioglitazone-induced gastroprotective effect in the cholestatic rats. Chronic treatment with pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of cholestatic rats compared to sham rats probably due to constitutive NOS induction and/or inducible NOS inhibition and attenuating release of TNF-α.
Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae-Caesalpinioideae), popularly known in Brazil as "caneleiro", is widely used in folk medicine against gastrointestinal diseases. In previous studies, the ethanol extract of leaves from C. macrophyllum Tul. var. acuminata Teles Freire had shown antinociceptive, anti-inflammatory, antibacterial, antioxidant and antiulcerogenic activities.
The aim of this study was to assess the gastroprotective effect of the hydroalcoholic fraction of leaves of C. macrophyllum Tul. var. acuminata Teles Freire (Cm-FHA), as well as to elucidate the possible underlying mechanisms of action.
Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity.The potential gastroprotective of Cm-FHA was assessed on different gastric ulcer models in rodents, such as absolute ethanol, HCl/ethanol, ischemia-reperfusion, cold restraint stress and indomethacin. The participation of prostaglandins, NO-synthase pathway and ATP-sensitive potassium channels (KATP) in gastroprotective activity of Cm-FHA were evaluated after treatment with a cyclooxygenase inhibitor (indomethacin), a NO-synthase inhibitor (L-NAME) and a KATP channel blocker (glibenclamide 5mg/kg), respectively. Likewise, the catalase activity was determinated in order to assess the possible participation of antioxidant mechanisms.
No sign of acute toxicity was observed after oral acute administration of Cm-FHA, considering the analyzed parameters. Likewise, Cm-FHA promoted a protective effect against gastric ulcers induced by absolute ethanol (lesion inhibition by 40% at both 100 and 200mg/kg), HCl/ethanol (lesion inhibition by 50 or 48% at 100 or 200mg/kg, respectively), ischemia-reperfusion (lesion reduction by 49 or 90% at 100 or 200mg/kg, respectively) and cold restraint stress (lesion inhibition by 63 or 76% at 100 or 200mg/kg, respectively), as well as a increase of catalase activity was observed. Otherwise, Cm-FHA was not able to protect gastric mucosa against indomethacin-induced lesions. Nitric oxide release, the of KATP channels opening and antioxidant activity are the possibly involved in the Cm-FHA-induced gastroprotective activity.
This study corroborates the folk medicine use of C. macrophyllum for treatment of gastric ulcers, as well as reinforces this species as a valuable source of promising natural drugs with gastroprotective activity.
MicroRNAs (miRNAs) have been shown to be closely associated with cellular apoptosis, but their involvement in response to ethanol-induced gastric mucosal epithelial cell apoptosis remains largely unknown. The purpose of this study was to investigate the expression profile of apoptosis-associated miRNAs in ethanol-induced acute gastric mucosal injury and the mechanisms underlying injury. Gastric mucosal injury was induced in rats by oral administration of ethanol, and gastric tissues were collected for analysis of gastric ulcer index, apoptosis ratio, caspase-3 activity, and miRNAs expression. Cell cultures of human gastric mucosal epithelial cells (GES-1) were incubated with ethanol to induce apoptosis. Mimics or inhibitors of miRNAs or c-Jun N-terminal kinase (JNK) inhibitor were added to the cell culture medium. GES-1 cells were collected for analysis of apoptosis ratio, caspase-3 activity, miRNAs expression, and protein phosphorylation levels of JNK, p38 mitogen-activated protein kinase (p38MAPK), or extracellular signal-regulated kinase (ERK). In the animal experiments, gastric ulcer index, cellular apoptosis, and caspase-3 activity were significantly increased, accompanied by up-regulation of miR-145 and down-regulation of the microRNAs miR-17, miR-19a, miR-21, miR-181a, and miR-200c. In the human cell culture experiments, the anti-apoptotic effects of miR-19a and miR-21 or pro-apoptotic effect of miR-145 were confirmed by their corresponding mimics or inhibitor; the ethanol-induced GES-1 apoptosis as well as the changes in miRNAs expression were significantly attenuated in the presence of JNK inhibitor. These results demonstrated that miR-145, miR-19a, and miR-21 were the apoptosis-associated miRNAs in gastric mucosal epithelial cells. The regulation of expression of these 3 miRNAs in ethanol-induced GES-1 apoptosis involved the JNK pathway.
Ethnopharmacological relevance:
Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer.
Aim of the study:
The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration.
Materials and methods:
Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods.
Results:
Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity.
Conclusion:
It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway.
Several human and experimental data suggest the particular importance of gastric protective processes in maintaining mucosal integrity. Both peripheral and central mechanisms are involved in this process. In the periphery, pre-epithelial mucus-bicarbonate layer, mucus, phospholipids, trefoil peptides, prostaglandins, heat shock proteins, sensory neuropeptides, nitric oxide, hydrogen sulfide may mediate mucosal protection. In the central nervous system hypothalamus and dorsal vagal complex (DVC) have particular important role in regulation of centrally-induced gastroprotection. Stimulation of paraventricular nuclei either aggravates or inhibits the mucosal injury depending on the ulcer model. Vagal nerve has also dual role, its activation can induce mucosal injury (by high dose of thyrotropin-releasing hormone (TRH), electrical stimulation), however, integrity of vagal nerve is necessary for gastroprotection induced either peripherally (by PGE2, prostacyclin, adaptive cytoprotection), or centrally (e.g. by neuropeptides). The centrally induced gastroprotection is likely to be vagally dependent, though vagal independent pathways have also been shown. Endomorphin-1 and endomorphin-2, selective μ-opioid receptor ligands, proved to be highly potent and effective gastroprotective agent in ethanol ulcer model (0.03-3 pmol intracerebroventricularly). Inhibition of the degradation of endomorphins by diprotin A resulted in gastroprotective effect, indicating the potential role of these endogenous opioids in the regulation of gastric mucosal integrity. Endomorphin-2 injected intracerebroventricularly restored the reduced levels of CGRP and somatostatin in gastric mucosa induced by ethanol. In conclusion, neuropeptides expressed in dorsal vagal complex and hypothalamus may have a regulatory role in maintaining gastric mucosal integrity by stimulating the formation of mucosal protective compounds.
An HPLC–PDA–ESI/MS/MS method was developed to identify the phytoconstituents of the EtOAc fraction of Eucalyptus gomphocephala DC. The antioxidant effect of the EtOAc fraction together with its sub-fractions was determined in vitro. The cytotoxicity was evaluated on different cell lines. The EtOAc fraction exhibited strong antioxidant activity, reduced the viability of all cell lines and was more active on MCF-7 and HepG-2 cell lines. Subsequently, the cytotoxicity of the sub-fractions and the isolated compounds were tested on MCF-7, HepG-2. The EtOAc fraction possessed potential antitumour promoting properties. It inhibited the stimulated NO (20%), 5-LOX (48.0%) and COX-2 (49.7%) respectively (at concentration of 20 lg/ml). This study suggests that this fraction is a source of different antioxidant and cytotoxic compounds with potential chemopreventive properties that might prevent different stages of the carcinogenesis process.
In vitro antifungal activity and phytochemical constituents of essential oil, aqueous, methanol and chloroform extract of Eucalyptus citriodora Hook leaves were investigated. A qualitative phytochemical analysis was performed for the detection of alkaloids, cardiac glycosides, flavonoids, saponins, sterols, tannins and phenols. Methanolic extract holds all identified biochemical constituents except for the tannin. While these biochemical constituents were found to be absent in essential oil, aqueous and chloroform extracts with the exception of sterols, cardiac glycosides and phenols in essential oil and sterols and phenols in aqueous and chloroform extracts. Antimycotic activity of four fractions of E. citriodora was investigated through agar-well diffusion method against four post-harvest fungi, namely, Aspergillus flavus Link ex Gray, Aspergillus fumigatus Fres., Aspergillus nidulans Eidam ex Win and Aspergillus terreus Thom. The results revealed maximum fungal growth inhibition by methanolic extract (14.5%) followed by essential oil (12.9%), chloroform extract (10.15%) and aqueous extract (10%).
Capsiate is a non-pungent analogue of capsaicin from CH-19 Sweet peppers. Capsaicin is reported to trigger calcitonin gene-related peptide (CGRP) release through activation of transient receptor potential vanilloid subfamily member 1 (TRPV1) and produces beneficial effects on gastric mucosa. This study aimed to investigate whether capsiate is able to produce beneficial effects on gastric mucosa and whether the protective effects of capsipate occur through a mechanism involving the activation of TRPV1 and CGRP release. A rat model of gastric mucosal injury was established by the oral administration of acidified ethanol. Gastric tissues were collected for analysis of the gastric ulcer index, cellular apoptosis, activities of caspase-3, catalase and superoxide dismutase (SOD), and levels of CGRP, TNF-α, and malondialdehyde (MDA). Our results show that the acute administration of ethanol significantly increased the gastric ulcer index concomitantly with an increase in cellular apoptosis, caspase-3 activity, and TNF-α and MDA levels, as well as a decrease in the activities of catalase and SOD. Pretreatment with 1 mg/kg capsiate attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by an increase in CGRP level, catalase, and SOD activities, and a decrease in caspase-3 activity, and TNF-α and MDA levels. The effects of capsiate were inhibited by capsazepine, an antagonist of TRPV1. These results suggest that capsiate is able to produce beneficial effects on ethanol-induced gastric mucosal injury. These effects are related to the stimulation of CGRP release through the activation of TRPV1.
The longstanding, successful use of herbal drug combinations in traditional medicine makes it necessary to find a rationale for the pharmacological and therapeutic superiority of many of them in comparison to isolated single constituents. This review describes many examples of how modern molecular-biological methods (including new genomic technologies) can enable us to understand the various synergistic mechanisms underlying these effects. Synergistic effects can be produced if the constituents of an extract affect different targets or interact with one another in order to improve the solubility and thereby enhance the bioavailability of one or several substances of an extract. A special synergy effect can occur when antibiotics are combined with an agent that antagonizes bacterial resistance mechanisms. The verification of real synergy effects can be achieved through detailed pharmacological investigations and by means of controlled clinical studies performed in comparison with synthetic reference drugs. All the new ongoing projects aim at the development of a new generation of phytopharmaceuticals which can be used alone or in combination with synthetic drugs or antibiotics. This new generation of phytopharmaceuticals could lend phytotherapy a new legitimacy and enable their use to treat diseases which have hitherto been treated using synthetic drugs alone.
A thiobarbituric acid (TBA) test procedure with reasonable reproducibility applicable to the assay of lipoperoxides in various animal tissue homogenates is described. It was concluded that the deproteinization of homogenate prior to coloration is not needed, but double wavelength measurement is necessary to avoid interference and the reaction should be performed with phosphoric acid at a definite pH near 2.0. The most reproducible procedure is as follows: To 0.5 ml of 10% homogenate of the tissue sample, add 3 ml of 1% H3PO4 and 1 ml of 0.6% TBA aqueous solution; stir and heat the mixture on a boiling water bath for 45 min. After cooling, add 4 ml of n-butanol, shake, and separate the butanol layer by centrifugation; determine the optical density of the butanol layer at 535 and 520 nm; and calculate the difference of optical density between the two determinations to be taken as the TBA value.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
Alternative processing of the RNA transcribed from the calcitonin gene appears to result in the production of a messenger RNA in neural tissue distinct from that in thyroidal 'C' cells. The thyroid mRNA encodes a precursor to the hormone calcitonin whereas that in neural tissues generates a novel neuropeptide, referred to as calcitonin gene-related peptide (CGRP). The distribution of CGRP-producing cells and pathways in the brain and other tissues suggests functions for the peptide in nociception, ingestive behaviour and modulation of the autonomic and endocrine systems. The approach described here permits the application of recombinant DNA technology to analyses of complex neurobiological systems in the absence of prior structural or biological information.
The gastroprotective effects of 70% acetone extracts of Quercus suber and Quercus coccifera leaves and of tannins (pedunculagin, castalagin, phillyraeoidin A, and acutissimin B) purified from these extracts were examined in the mouse using the ethanol-induced gastric ulcer model. Both extracts (25, 50, and 100 mg/kg), given orally, prevented the formation of ethanol-induced lesions in the stomach. The percent protection varied between 68 and 91%. Purified tannins (50 mg/kg) were also effective in protecting the stomach against ethanol, and the percent protection varied from 66 to 83%. Castalagin was the most potent. Both extracts and all of the tannins tested (10, 25, and 50 microg/mL) strongly inhibited (55-65%) the lipid peroxidation of rabbit brain homogenate. These results suggest that the gastroprotective effects of extracts of Q. suber and Q. coccifera leaves and the purified tannins in this experimental model are related to their anti-lipoperoxidant properties.
A water-soluble (at pH 8) aromatic disulfide [5,5′-dithiobis(2-nitrobenzoic acid)] has been synthesized and shown to be useful for determination of sulfhydryl groups.Several applications have been made to show its usefulness for biological materials.A study of the reaction of this disulfide with blood has produced some evidence for the splitting of disulfide bonds by reduced heme.
An extraction procedure and an analytical method have been developed to detect and quantify for the first time a series of ellagitannin derivatives formed in wine during aging in oak barrels. The method involves a preliminary purification step on XAD7 HP resin followed by a second purification step on TSK 40 HW gel. The resulting extract is analyzed for compound identification and quantitative determination by high-performance liquid chromatography-electrospray ionization-mass spectrometry in single ion recording mode. Reference compounds, which are accessible through hemisynthesis from the oak C-glycosidic ellagitannin vescalagin, were used to build calibration curves, and chlorogenic acid was selected as an internal standard. This method enabled us to estimate the content of four flavano-ellagitannins and that of another newly identified wine polyphenol, beta-1-O-ethylvescalagin, in a Bordeaux red wine aged for 18 months in oak barrels. All five ellagitannin derivatives are derived from the nucleophilic substitution reaction of vescalagin with the grape flavan-3-ols catechin and epicatechin or ethanol.
C-glucosidic ellagitannin dimers were classified as types A-C according to a putative biogenetic oligomerization mode. They were characterized by different positions of the C-C bond between the phenolic acyl unit in one monomer and the benzylic C-1 of the open-chain glucose core in the other monomer. In recent years, four C-glucosidic tannins, melasquanins A-D (18-21), have been found in the leaves of Melaleuca squarrosa Donn ex Sm. (Myrtaceae). These are characterized as a dimer (melasquanin A) of a dimerization mode (type D), and trimers (melasquanins B-D) based on spectroscopic analysis including various two-dimensional nuclear magnetic resonance (2D NMR) experiments. Melasquanins B (19) and D (21) are C-glucosidic tannin trimers with a structure containing, non-repeating condensation modes, which was hitherto unknown.
A direct HPTLC assay was developed for the determination of total curcuminoids and three individual curcuminoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin. In addition, a new procedure was developed to separate and quantitative the free radical-scavenging activity of individual compounds from the rhizome of Curcuma longa L. (Zingiberaceae) based on the combination of HPTLC with a diode array detector (DAD) and post chromatographic DPPH(*) radical derivatisation. It was established that both individual curcuminoids and the extract of C. longa were capable of scavenging DPPH(*) radicals. From the estimated ID(50) values, it can be seen that the order of activity was curcumin > demethoxycurcumin > bisdemethoxycurcumin > ascorbic acid. However, the ID(50) values of curcuminoids were not significantly different. The data indicates the presence of a synergistic mechanism of antiradical activity of curcuminoids.
Blackberries ( Rubus sp.) were evaluated by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) to identify the ellagitannins present in flesh, torus (receptacle tissue), and seeds. Most ellagitannins were present (or detectable) only in seed tissues. Ellagitannins identified by HPLC-ESI-MS in the seeds included pedunculagin, casuarictin/potentillin, castalagin/vescalagin, lambertianin A/sanguiin H-6, lambertianin C, and lambertianin D. For several of the ellagitannins, isomeric separation was also obtained. The MALDI-TOF-MS analysis was primarily utilized to evaluate and identify high molecular mass (>1000 Da) ellagitannins. The MALDI analysis verified the presence of the ellagitannins identified by HPLC-ESI-MS including lambertianin A/sanguiin H-6, lambertianin C, and lambertianin D, but the analysis also indicated the presence of several other compounds that were most likely ellagitannins based on the patterns observed in the masses (i.e., loss or addition of a gallic acid moiety to a known ellagitannin). This study determined the presence of several possible isomeric forms of ellagitannins previously unidentified in fruit and presents a possible analytical HPLC method for the analysis of the major ellagitannins present in the fruit.
Dodonaea viscosa Linn. (Sapindaceae) is used as a medicinal herb by the tribes of Shola forest regions of Western Ghats. It is used for headaches, backaches, stomach pain, piles and simple ulcers. The present study was performed to evaluate the gastroprotective effect and acute toxicity of this plant in various experimental models.
Studies were performed in two different models (ethanol and indomethacin induced gastric ulcer) in wistar rats. Gastric protection was evaluated by measuring the ulcer index, gastric glutathione assay, alkaline phosphate assay and histopathological studies. Gastric secretion studies were done by pyloric ligation experiment.
Water and ethanol extract (500 mg/kg body weight) showed moderate activity compared to hexane extract. Hexane extract of Dodonaea viscosa dose dependently inhibited ethanol induced gastric lesions, causing 90% protection at 500 mg/kg, 81% protection at 250 mg/kg, and 70% protection at 125 mg/kg and it also dose dependently inhibited indomethacin induced gastric lesions, causing 92% protection at 500 mg/kg, 77% protection at 250 mg/kg, and 52% protection at 125 mg/kg. The various degrees of inhibition were statistically significant (p<or=0.05). Further in our gastric secretion studies, we found that hexane extract of Dodonaea viscosa (500 mg/kg) decreased the amount of total acid in gastric juice. Dodonaea viscosa hexane extract thus inhibits acid secretion to prevent ulcer aggravation. Acute toxicity study with a higher dose of 1250 mg/kg did not manifest any toxicological signs in rats. We also performed preliminary phytochemical screening of the crude extract which gave positive results for the presence of flavanoids, saponins, bitter principles and phenols.
Both IL-1 and TNF-␣ levels were assessed using
- Tnf-␣ Raybio
- Elisa
and 5-LO in the stomach homogenate of the different groups. Both IL-1 and TNF-␣ levels were assessed using RayBio ® Rat IL-1 and RayBio ® Rat TNF-␣ ELISA Kits (RayBiotech, Inc., Norcross, GA, USA), respectively. COX-2 and 5-LO tissue levels were estimated using Rat COX-2 Assay Kit (Immuno-Biological Laboratories Co., Ltd, Minneapolis, USA) and Rat 5-LO ELISA kits (EIAab, Science Co., Ltd., Wuhan, China), respectively. The steps were carried out according to the manufacturer's instructions. Assessment of caspase-3
Theory and Practice of Histological Techniques
- J D Banchroft
- A Stevens
- D R Turner
Banchroft, J.D., Stevens, A., Turner, D.R., 1996. Theory and Practice of Histological Techniques, Fourth ed. Churchil Livingstone, New York/London/San
Francisco/Tokyo.
a , b , c , d 8.68 ± 0.20 a , b , c , d ECF (50 mg/kg) 25.17 ± 0.29 a , b , c 27 a , b , d Data are expressed as means ± SEM (n = 6) IL-1, interleukin-1 beta; TNF-, tumor necrosis factor-alpha; 5-LO, 5-lipoxygenase Gastroprotective mechanism of Bauhinia thonningii Schum
- J J Jayapalan
- O H Hashim
Negative control
17.30 ± 0.80 b, c
20.83 ± 0.82 b, c
5.35 ± 0.28 b, c
2.72 ± 0.16 b, c
Ulcer control
73.32 ± 4.84 a, c
80.92 ± 4.74 a, c
28.48 ± 1.10 a, c
20.73 ± 0.75 a, c
ECF (25 mg/kg)
28.83 ± 0.79 a, b, c
38.27 ± 0.94 a, b, c, d
13.70 ± 0.44 a, b, c, d
8.68 ± 0.20 a, b, c, d
ECF (50 mg/kg)
25.17 ± 0.29 a, b, c
27.80 ± 0.54 a, b, c
8.38 ± 0.29 a, b, c
5.05 ± 0.12 a, b, c
ECF (100 mg/kg)
16.60 ± 0.76 b, c, d
20.80 ± 0.82 b, c, d
4.90 ± 0.20 b, c, d
2.30 ± 0.17 b, c, d
Omeprazole (20 mg/kg)
43.00 ± 1.93 a, b, d
50.32 ± 1.74 a, b, d
19.70 ± 0.41 a, b, d
13.25 ± 0.32 a, b, d
Data are expressed as means ± SEM (n = 6). IL-1, interleukin-1 beta; TNF-, tumor necrosis factor-alpha; 5-LO, 5-lipoxygenase; COX-2, cyclooxygenase 2.
a Significantly different from the negative control group at p < 0.05.
b Significantly different from the ulcer control group at p < 0.05.
c Significantly different from the omeprazole group at p < 0.05.
d Significantly different from the corresponding group treated with ECF 50 mg/kg at p < 0.05.
References
Abdelwahab, S.I., Taha, M.M.E., Abdulla, M.A., Nordin, N., Hadi, A.H.A., Mohan, S.,
Jayapalan, J.J., Hashim, O.H., 2013. Gastroprotective mechanism of Bauhinia thonningii Schum. J. Ethnopharmacol. 148, 277–286.
Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa
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- F Bonamin
- Dos Santos
- R C Périco
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- F P De Sousa
- D P Filho
- J M Da Rocha
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de Carvalho, K.I., Bonamin, F., Dos Santos, R.C., Périco, L.L., Beserra, F.P., de Sousa, D.P.,
Filho, J.M., da Rocha, L.R., Hiruma-Lima, C.A., 2014. Geraniol-a flavoring agent
with multifunctional effects in protecting the gastric and duodenal mucosa.
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