Gastroprotective activity of epitaondiol and sargaol

The effects of epitaondiol (1) and sargaol (2), isolated from the brown alga Stypopodium flabelliforme on HCl/ethanol-induced gastric lesions in mice were evaluated and compared with that of lansoprazole. Epitaondiol and sargaol (6.25 - 50 mg/kg) dose-dependently inhibited the appearance of gastric lesions in mice, displaying similar values to lansoprazole at 20 mg/kg. Both epitaondiol and sargaol showed gastroprotective activity with ED50 values of 40 mg/kg and 35 mg/kg, respectively. The results suggest that epitaondiol and sargaol protect the gastric mucosa in the HCl/EtOH model in mice.     

Effects of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal injuries in Sprague-Dawley rats

Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control) rats were orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer control) rats were also orally administered with vehicle. Group 3 (positive control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-induced gastric mucosal injury was studied grossly and histology. The level of lipid peroxidation (malondialdehyde-MDA), superoxide dismutase (SOD) and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-induced gastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may possibly be due to its preservation of gastric wall mucus along with increased SOD activity and reduction of oxidative stress (MDA). The extract is non-toxic, even at relatively high concentrations.     

Gastroprotective Activities of Ethanol Extract of Black Rice Bran (Oryza sativa L.) in Rats

Black rice is a type of rice in the Oryza sativa L. species. There are numerous reports regarding the pharmacological actions of black rice bran, but scientific evidence on its gastroprotection is limited. This study aimed to evaluate the gastroprotective activities of black rice bran ethanol extract (BRB) from the Thai black rice variety Hom Nil (O. sativa L. indica) as well as its mechanisms of action, acute oral toxicity in rats, and phytochemical screening. Rat models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress were used. After pretreatment with 200, 400, and 800 mg/kg of BRB in test groups, BRB at 800 mg/kg significantly inhibited the formation of gastric ulcers in all gastric ulcer models, and this inhibition seemed to be dose dependent in an indomethacin-induced gastric ulcer model. BRB could not normalize the amount of gastric wall mucus, reduce gastric volume and total acidity, or increase gastric pH. Although BRB could not increase NO levels in gastric tissue, the tissue MDA levels could be normalized with DPPH radical scavenging activity. These results confirm the gastroprotective activities of BRB with a possible mechanism of action via antioxidant activity. The major phytochemical components of BRB comprise carotenoid derivatives with the presence of phenolic compounds. These components may be responsible for the gastroprotective activities of BRB. The 2000 mg/kg dose of oral BRB showed no acute toxicity in rats and confirmed, in part, the safe uses of BRB.     

Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.     

Gastroprotection of Suaveolol, Isolated from <em>Hyptis suaveolens</em>, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg), and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg) was attenuated by pretreatment with either N^G-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.     

Anti-ulcer effect in rats of bitter cardamon constituents

The effects of bitter cardamon (the fruit of Alpinia oxphylla), used as a medicine and a condiment, on HCl/ethanol-induced gastric lesions in rats were examined. The acetone extract at 50 mg/kg, p.o. significantly inhibited gastric lesions by 57.0%. An analysis of the active constituents in the acetone extract was performed using column chromatography. Nootkatone at 20 mg/kg, p.o. significantly inhibited gastric lesion. These results suggest that nootkatone, the sesquiterpenoid is an important constituent in stomach medications containing bitter cardamon.     

Copper nanoparticles supported on polyethylene glycol-modified magnetic Fe3O4 nanoparticles: Its anti-human gastric cancer investigation

In that work, we have described the synthesis of novel Cu NPs decorated polyethylene glycol (PEG₂₀₀₀) coated magnetic nanoparticles (Fe₃O₄/PEG2000/Cu NPs) in an eco-friendly pathway applying Green Tea extract as reducing/stabilizing agent. The morphological and physicochemical features of the prepared nanocomposite were determined using several advanced techniques like ICP-OES, FE-SEM, EDX, atomic mapping, TEM, VSM, and XRD studies. In the antioxidant test, the IC50 of Fe₃O₄/PEG₂₀₀₀/Cu nanocomposite and BHT against DPPH free radicals were 198 and 85 µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with Fe₃O₄/PEG₂₀₀₀/Cu nanocomposite were assessed by MTT assay for 48 h about the cytotoxicity and anti-human gastric cancer properties on normal (HUVEC) and gastric cancer cell lines i.e. NCI-N87 and MKN45. The IC50 of Fe₃O₄/PEG₂₀₀₀/Cu nanocomposite were 316 and 131 µg/mL against NCI-N87 and MKN45 cell lines, respectively. The viability of malignant gastric cell line reduced dose-dependently in the presence of Fe₃O₄/PEG₂₀₀₀/Cu nanocomposite. It seems that the anti-human gastric cancer effect of recent nanoparticles is due to their antioxidant effects.     

Gastroprotective potentials of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats

This study investigated the protective effects of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats. Gastric ulceration was induced by single intraperitoneal injection of indomethacin (30 mg/kg b.wt.). M. maderaspatana extract produced significant reduction in gastric mucosal lesions, malondialdehyde and serum tumour necrosis factor-α associated with a significant increase in gastric juice mucin content and gastric mucosal catalase, nitric oxide and prostaglandin E2 levels. The volume and acidity of the gastric juice decreased in pretreated rats. The plant extract was evaluated in the gastric juice of rats, untreated has showed near normal levels in pretreated rats. The M. maderaspatana was able to decrease acidity and increase the mucosal defence in the gastric area, therefore justifying its use as an antiulcerogenic agent. Ranitidine significantly increased pH value and decreased pepsin activity and gastric juice free and total acidity. The anti-ulcer effect was further confirmed histologically.     

6-Gingesulfonic acid, a new anti-ulcer principle, and gingerglycolipids A, B, and C, three new monoacyldigalactosylglycerols, from zingiberis rhizoma originating in Taiwan.

By monitoring the effects on HCl/ethanol-induced gastric lesions in rats, a new antiulcer principle named 6-gingesulfonic acid was isolated from Zingiberis Rhizoma, the dried rhizome of Zingiber officinale Roscoe (cultivated and processed in Taiwan) together with three new monoacyldigalactosylglycerols named gingerglycolipids A, B and C. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. 6-Gingesulfonic acid showed more potent anti-ulcer activity than 6-gingerol and 6-shogaol.     

Synthesis of Halogenated 1,5-Diarylimidazoles and Their Inhibitory Effects on LPS-Induced PGE2 Production in RAW 264.7 Cells

A series of halogenated 1,5-diarylimidazole compounds were synthesized and their inhibitory effects on LPS-induced PGE₂ production in RAW 264.7 cells were evaluated. A wide variety of 2,4-, 4-, and 2-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles were synthesized for SAR study via two different pathways. Overall, 4-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles, regardless of the species of halogen, exhibited very strong inhibitory activities of PGE₂ production. Among them, 4-chloro-5-(4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole (3, IC₅₀ 3.3 nM ± 2.93), and 4-chloro-5-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)imidazole (13, IC₅₀ 5.3 nM ± 0.23) showed the best results.     

The Vital Role of Buffer Anions in the Antioxidant Activity of CeO2 Nanoparticles

Cerium oxide (CeO₂) nanoparticles display excellent antioxidant properties by scavenging free radicals. However, some studies have indicated that they can cause an adverse response by generating reactive oxygen species (ROS). Hence, it is important to clarify the factors that affect the oxidant/antioxidant activities of CeO₂ nanoparticles. In this work, we report the effects of different buffer anions on the antioxidant activity of CeO₂ nanoparticles. Considering the main anions present in the body, Tris‐HCl, sulfate, and phosphate buffer solutions have been used to evaluate the antioxidant activity of CeO₂ nanoparticles by studying their DNA protective effect. The results show that CeO₂ nanoparticles can protect DNA from damage in Tris‐HCl and sulfate systems, but not in phosphate buffer solution (PBS) systems. The mechanism of action has been explored: cerium phosphate is formed on the surface of the nanoparticles, which interferes with the redox cycling between Ce³⁺ and Ce⁴⁺. As a result, the antioxidant activity of CeO₂ nanoparticles is greatly affected by the external environment, especially the anions. These results may provide guidance for the further practical application of CeO₂ nanoparticles.     

Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages,HCl/EtOH-induced Gastritis,and LPS-induced Lung Injury via Attenuation of Src and TAK1

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE₂, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.     

Synthesis, gastroprotective effect and cytotoxicity of new amino acid diterpene monoamides and diamides

Following our studies on the gastroprotective effect and cytotoxicity of terpene derivatives, new amides were prepared from the diterpene 8(17)-labden-15,19-dioic acid (junicedric acid) and its 8(9)-en isomer with C-protected amino acids (amino acid esters). The new compounds were evaluated for their gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice, as well as for cytotoxicity using the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma cells (AGS) and liver hepatocellular carcinoma (Hep G2). A dose-response experiment showed that at 25 mg/kg the C-15 leucyl and C-15,19-dileucylester amides of junicedric acid reduced gastric lesions by about 65.6 and 49.6%, respectively, with an effect comparable to lansoprazole at 20 mg/kg (79.3% lesion reduction). The comparison of the gastroprotective effect of 18 new amino acid ester amides was carried out at a single oral dose of 25 mg/kg. Several compounds presented a strong gastroprotective effect, reducing gastric lesions in the 70.9-87.8% range. The diprolyl derivative of junicedric acid, the most active product of this study (87.8% lesion reduction at 25 mg/kg) presented a cytotoxicity value comparable with that of the reference compound lansoprazole. The structure-activity relationships are discussed.     

The gastroprotective effect of oxycellulose pellets on gastric ulcers

Oxycellulose belongs to the wide range of pharmaceutically and medically used cellulose derivatives unique in its properties of biodegradability, non-toxicity, antioxidative activity, haemostasis supporting, tissue healing improvement, etc. Glycyrrhizin (Gly) represents the most prominent licorice triterpenoid glycoside, which is responsible for its pharmacological activity, and is closely linked to increasing levels of gastroprotective prostaglandins. In order to study the anti-ulcer activity of oxycellulose sodium and Gly, pellets containing only oxycellulose, or in combination with glycyrrhizin, were prepared using an extrusion/spheronization method. The physical properties and in vitro release rate of the prepared pellets were tested. Based on the obtained results, one sample prepared from oxycellulose only, and one containing glycyrrhizin were chosen for in vivo testing. The healing effect of the prepared pellet formulations was evaluated in the acetic acid induced gastric ulcers in rats. The improvement in gastric ulcer healing was documented for myeloperoxidase activity, alkaline phosphatase activity and gastric wall mucin levels using the Alcian blue binding capacity. The tested pellets significantly reduced myeloperoxidase and alkaline phosphatase activity, and increased gastric wall mucus levels compared to the non-treated group. The in vivo tests showed that oral administration of the prepared pellets accelerated the healing of gastric ulcers in rats.     

TEA CO2 laser-induced reaction of CH3NO2 with CF2HCl: A mechanistic study

Dissociation of nitromethane has been observed when a mixture of CF₂HCl and CH₃NO₂ is irradiated using pulsed TEA CO₂ laser at 9R (24) line (1081 cm^-1), which is strongly absorbed by CF₂HCl but not by CH₃NO₂. Under low laser fluence conditions, only nitromethane dissociates, whereas at high fluence CF₂HCl also undergoes dissociation, showing that dissociation occurs via the vibrational energy transfer processes from the TEA CO₂ laser-excited CF₂HCl to CH₃NO₂. Time-resolved infrared fluorescence from vibrationally excited CF₂HCl and CH₃NO₂ molecules as well as UV absorption of CF₂ radicals are carried out to elucidate the dynamics of excitation/dissociation and the chemical reactions of the dissociation products.     

Bioassay-guided isolation of an anti-ulcer compound, tagitinin C, from Tithonia diversifolia: role of nitric oxide, prostaglandins and sulfhydryls

Tithonia diversifolia is a medicinal plant from the Municipality of Suchiapa, Chiapas, Mexico, that according to local folk medicine is considered useful in the treatment of gastric ulcers. The aim of the present study was to investigate the gastroprotective activity of T. diversifolia by using an ethanol-induced gastric ulcer experimental model in male Wistar rats. The results showed that T. diversifolia had gastroprotective activity, and that the dichloromethane extract had the highest protective activity (close to 90% when using doses between 10 to 100 mg/kg), and that further the compound tagitinin C isolated from this extract was the main active gastroprotective agent. Rats treated with tagitinin C suspended in Tween 80 at 1, 3, 10 and 30 mg/kg showed 37.7, 70.1, 100, and 100% gastroprotection, respectively. The effect elicited by tagitinin C (30 mg/kg) was not attenuated by pretreatment with either N(G)-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups, or indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, which suggests that the gastroprotective mechanism of action of this sesquiterpene lactone does not involve NO, sulfhydryl groups or prostaglandins.     

Gold-vanadium-niobium catalysts in environmental protection—adsorption and interaction of NO, C3H6 and O2—FT-IR study

FT-IR study of NO and C₃H₆ adsorption, co-adsorption and interaction in the presence of oxygen were performed in order to estimate the catalytic behaviour of Au and V-containing MCM-41 materials in NO-SCR with propene. MCM-41 were modified with gold, vanadium and niobium by their introduction during the synthesis (co-precipitation) carried out with the use of HCl or H₂SO₄ as pH adjustment agent. The texture/structure properties of the prepared samples were investigated by N₂ adsorption, XRD, XPS and TEM techniques. It has been found that the nature of acid used for the pH adjustment during the synthesis determines the gold particles size and dispersion and influences the interaction of NO+O₂+C₃H₆ with the catalyst surfaces. In both types of AuVMCM-41 catalysts, the SCR reaction route occurs via NO₂ formation. In the case of AuVMCM-41(HCl) and AuVNbMCM-41(HCl) nitrites are formed and stored, and upon heating NO₂ is released. These kinds of nitrites are not formed on AuVMCM-41(H₂SO₄) and AuVNbMCM-41(H₂SO₄). Instead of that NO₂ is chemisorbed on metallic gold, niobium and vanadium species and reacts with propene and/or oxygenates.     

Synthesis and protective effect of 1,3,5-triazine derivatives, leukotriene C4 antagonist, on HCl.ethanol-induced gastric lesions in rats.

2,4-Diamino-[E]-6-[2-(3-pyridyl)ethenyl]-1,3,5-triazine (3a), leukotriene C4 (LTC4) antagonist, was found to possess a protective effect on HCl.ethanol-induced gastric lesions. Analogues of 3a were synthesized and evaluated for the effect as well as antagonistic activity against LTC4-induced contraction. Seven compounds (3a-d, f-h) exhibited a potent protective effect on gastric lesions which was considered to be based on the antagonistic activity against LTC4. The structure-activity relationships of the derivatives (3a-k) are discussed.     

Anti-ulcer effects of Trichosanthes fruits

Anti-ulcer activities of fruits of Trichosanthes kirilowii Maximowicz var. japonica Kitamura (50% ethanolic extract, TKE) were investigated in rats. TKE, at doses of 100-1000 mg/kg, showed potent protection against experimental gastric lesions, namely, those induced by water-immersion, histamine, serotonin, HCl.ethanol, 0.6 N HCl, 0.2 N NaOH, 35% NaCl, and Shay' ulcer and acetic acid-induced gastric ulcer. At doses of 500-1000 mg/kg, TKE decreased the gastric secretion and acid output in pylorus-ligation (for 7 h), but 100 mg/kg of TKE had no influence on the gastric secretion. On the other hand, TKE exerted inhibition on the contractile responses of the isolated ileum of mouse to acetylcholine. These results suggested that TKE has an anti-ulcer effect.     

Separation of Prostaglandins E1, and E2 and other Major Eicosanoids by Unidimensional Argentation Thin Layer Chromatography

Abstract

Prostaglandins (PG) E₁ and E₂ are important regulators of biologic functions, and can express different biological effects. In thin layer chromatography (TLC) systems which separate these compounds, comigration of other major eicosanoids is a problem. This paper describes a TLC system using a mobile phase of chloroform/methanol/acetic acid/H₂O (90:7.5:5:0.8) that separates PGE₁ and PGE₂, as well as other major eicosanoids, including dihomogammalinolenic acid (DHLA), the immediate fatty acid precursor of PGE₁.