Comparative Inhibitory Efficacy on the iNOS/NO System of Curcumin- and Tetrahydrocurcumin-Self-Microemulsifying Liquid Formulation in Chronic Gastric Ulcer Model

2020 ◽  
Vol 21 ◽  
Author(s):  
Sirima Mahattanadul ◽  
Sonsawan Kongpuckdee ◽  
Ruedeekorn Wiwattanapatapee ◽  
Pimpimon Tansakul ◽  
Anupong Nitiruangjaras ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Oral Administration ◽  
Mrna Expression ◽  
Ulcer Healing ◽  
Inhibitory Effect ◽  
Inos Mrna ◽  
Antiulcer Activity ◽  
No Production ◽  
Liquid Form ◽  
Ulcer Model

Background: Curcumin was found to accelerate gastric ulcer healing by a main mechanism through suppression of iNOS mediated inflammation. Although tetrahydrocurcumin (THC) is claimed as an active antioxidant principle of curcumin, its antiulcer activity has not been systematically examined. The utility of self- microemulsifying drug delivery systems (SMEDDS) for curcumin and THC formulations in liquid form was also found to increase the rate and extent of release of curcumin- and THC-SMEDDS. Nevertheless, the beneficial antiulcer efficacy of these nanoproducts has not yet been evaluated. Objective: This study aimed to evaluate and compare antiulcer efficacy of curcumin- and THC-SMEDDS through inhibition of the iNOS/NO system in rat model. Methods: Antiulcer efficacy was compared in terms of an ability to accelerate the healing of gastric ulcerincluding the inhibitory efficacy on inflammatory NO production in activated macrophages and iNOS mRNA expression at the ulcerated area. Results: THC was found to have less ulcer healing capacity than curcumin with a lack of significant inhibitory effect on the iNOS/NO system. SMEDDS used in the study significantly increased the inhibitory efficacy of THC on iNOS/NO production and iNOS mRNA expression into a comparable inhibitory potency to that of curcumin. An oral administration of curcumin- or THC-SMEDDS once a day was capable of exerting a comparable curative efficacy to a twice-daily oral administration of curcumin or THC. Conclusion: The SMEDDS used in the study could bring an enhancement of inhibitory efficacy on the iNOS/NO system of antiulcer drug, leading to a reduction of daily dosing and dosing frequency.

Role of nuclear factor-κB in gastric ulcer healing in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1296-G1304 ◽  
Author(s):  
Satoru Takahashi ◽  
Takuya Fujita ◽  
Akira Yamamoto
Keyword(s):  
Gastric Ulcer ◽  
Mrna Expression ◽  
Ulcer Healing ◽  
Nuclear Factor Κb ◽  
Normal Mucosa ◽  
Cyclooxygenase 2 ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Gastric Ulcer Healing

We investigated the role of nuclear factor-κB (NF-κB) in gastric ulcer healing in rats. NF-κB was activated in ulcerated tissue but not in normal mucosa, and the level of the activation was decreased with ulcer healing. NF-κB activation was observed in fibroblasts, monocytes/macrophages, and neutrophils. Treatment of gastric fibroblasts, isolated from the ulcer base, with interleukin-1β activated NF-κB and the subsequently induced cyclooxygenase-2 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA expression. Inhibition of activated NF-κB action resulted in suppression of both their mRNA expression and increases in PGE2 and CINC-1 levels induced by interleukin-1β. Persistent prevention of NF-κB activation caused an impairment of ulcer healing in rats. Gene expression of interleukin-1β, CINC-1, cyclooxygenase-2, and inducible nitric oxide synthase in ulcerated tissue had been inhibited before the delay in ulcer healing became manifest. The increased levels of cyclooxygenase-2 protein and PGE2 production were also reduced. These results demonstrate that NF-κB, activated in ulcerated tissue, might upregulate the expression of healing-promoting factors responsible for gastric ulcer healing in rats.

scholarly journals ANTIOXIDANT AND GASTRIC ULCER HEALING EFFECT OF ORTHOSIPHONSTAMINEUS (BENTH.) LEAVES EXTRACT IN ASPIRIN-INDUCED RATS

2017 ◽  
Vol 10 (2) ◽  
pp. 397 ◽  
Author(s):  
Ari - Yuniarto
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
Control Group ◽  
Histopathological Analysis ◽  
Antiulcer Activity ◽  
Gastric Ulcer Healing ◽  
Orthosiphon Stamineus ◽  
Mucosal Integrity ◽  
Healing Effect ◽  
Dpph Method

Objective: In the gastrointestinal system, gastric ulcer is one of the common serious problems in human life and gives contribution against morbidity and mortality incidence. The pathophysiology of gastric ulcer is an imbalance between aggressive factor and mucosal integrity factor. Increase of aggressive factors and decrease of mucosal integrity factors have potential against developed of gastric ulcer disease. The objective of the research was to evaluate antioxidant and gastric ulcer healing effect of Orthosiphon stamineus (Benth.) leaves extract in aspirin-induced rats.Methods: In vivo antiulcer activity of Orthosiphon leaves extract was evaluated through several parameters involves gastric acidity, number of ulcers, diameters of ulcers, ulcer index (UI), and healing ratio. Dose level of Orthosiphon leaves extract which used in this study such as 250 and500 mg/kg, respectively. Antioxidant activity of Orthosiphon leaves extract was evaluated by 1,1-diphenyl-2-picrylhydrazyl hydrate (DPPH) method. Histopathological of the stomach was performed using hematoxylin-eosin stained.Results: The results of the study showed that groups which given Orthosiphon leaves extract have significantly different for gastric ulcer healing compared to the control group and were supported by histopathological analysis. The Orthosiphon leaves extract also showed maximum scavengingactivity at a concentration of 100 µg/ml (58.86% inhibition) and minimum at 50 μg/ml (29.60% inhibition) with inhibitory concentration 50% (IC  )50 84.54 µg/ml when compared to ascorbic acid as the standard with IC5.08 µg/ml by DPPH method.Conclusion: It can be concluded that from the experimental study of O. stamineus (Benth.) leaves extract has potential antiulcer activity in aspirin- induced rats model and antioxidant effect using DPPH method. Stomach tissues regeneration in gastric ulcer model might be affected by the improvement of antioxidant status.Keywords: Orthosiphon stamineus (Benth.), Extract, Ulcer, Aspirin, 1,1-diphenyl-2-picrylhydrazyl hydrate.

Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity: implications for glomerulonephritis

1997 ◽  
Vol 272 (6) ◽  
pp. F721-F728 ◽  
Author(s):  
E. A. Jaimes ◽  
K. A. Nath ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Inos Mrna ◽  
No Production ◽  
Glomerular Injury ◽  
Inos Activity ◽  
Oxide Synthase

In glomerulonephritides, autacoids such as nitric oxide (NO), reactive oxygen species, and prostanoids are produced in increased amounts in response to cytokines such as interleukin-1 (IL-1). These autacoids influence the expression of glomerular injury by their direct as well as interactive actions. We studied the effect of hydrogen peroxide (H2O2) on NO production in rat mesangial cells. We demonstrate that transient exposure of mesangial cells to H2O2 prior to sustained exposure to IL-1 decreased extracellular accumulation of NO2/NO3 and cellular guanosine 3,'5'-cyclic monophosphate (cGMP) content. H2O2 markedly impaired inducible nitric oxide synthase (iNOS) activity induced by IL-1 directly measured by the conversion of L-[14C]arginine to L-[14C]citrulline. Such impairment in iNOS activity was accompanied by a parallel reduction in iNOS protein abundance but not by a reduced expression of iNOS mRNA. The inhibitory effect of H2O2 on NOS activity was further supported by peroxide-induced impairment in IL-1-driven, NO-dependent synthesis of prostaglandin E2. Our studies thus provide the first direct evidence of a posttranscriptional inhibitory effect of H2O2 on iNOS activity. Additionally, our studies uncover the existence of a previously unrecognized effect of H2O2 on the production of NO that may exert influence on the severity of glomerular injury during glomerular inflammation.

Enhanced Expression of Inducible Nitric Oxide Synthase by Juzen-Taiho-To in LPS-Activated RAW264.7 Cells, a Murine Macrophage Cell Line

2000 ◽  
Vol 28 (02) ◽  
pp. 217-226 ◽  
Author(s):  
Hiroshi Kawamata ◽  
Hiroshi Ochiai ◽  
Naoki Mantani ◽  
Katsutoshi Terasawa
Keyword(s):  
Nitric Oxide ◽  
Mrna Expression ◽  
Cell Line ◽  
Raw264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Murine Macrophage ◽  
Macrophage Cell Line ◽  
Macrophage Cell ◽  
Murine Macrophage Cell Line

We have investigated the effect of Juzen-taiho-to (TJ-48) on inducible NO synthase (iNOS) expression and nitric oxide (NO) production in RAW264.7 cells, a murine macrophage cell line. TJ-48-lipopolysaccharide (LPS) combination induced iNOS mRNA expression earlier, stronger and remained longer that paralleled but with a higher NO production compared to LPS stimulation. TJ-48 itself showed no inducible effect either no NO production or iNOS mRNA expression. This phenomenon could be considered to contribute, at least in part, to the beneficial effects of TJ-48 through the iNOS-mediated activation of biodefense mechanism.

Heregulin-α and heregulin-β expression is linked to a COX-2-PGE2 pathway in human gastric fibroblasts

2006 ◽  
Vol 290 (6) ◽  
pp. G1243-G1251 ◽  
Author(s):  
Kazuhiro Nagata ◽  
Ken Wada ◽  
Atsushi Tatsuguchi ◽  
Seiji Futagami ◽  
Katya Gudis ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Growth Factor ◽  
Mrna Expression ◽  
Repair Process ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Real Time Quantitative Pcr ◽  
Growth Factor Production ◽  
Cox 2 ◽  
Stimulation Of

We have previously shown heregulin (HRG)-α expression in human gastric fibroblasts and its stimulation of gastric epithelial cell growth. Although cyclooxygenase (COX)-2 has also been shown to stimulate growth factor production in these cells, the interaction between COX-2 and HRG remains unknown. Conditioned media (CM) from gastric fibroblasts incubated with PGE2 or interleukin (IL)-1β, a well known COX-2 inducer, were analyzed for their effect on erbB3 tyrosine phosphorylation in MKN28 gastric epithelial cells. HRG protein expression in fibroblast lysates and CM was also examined by western blot. HRG-α and HRG-β mRNA expression in gastric fibroblasts and human gastric tissue was examined by real-time quantitative PCR. HRG and COX-2 expressions in surgical resections of human gastric ulcer tissue were examined immunohistochemically. CM from fibroblasts incubated with PGE2, or IL-1β, stimulated erbB3 phosphorylation in MKN28 cells. Preincubation of the fibroblasts with celecoxib, a selective COX-2 inhibitor, suppressed CM-induced erbB3 phosphorylation. This inhibition was reversed by exogenous PGE2. As with erbB3 phophorylation, IL-1β stimulated both HRG-α and HRG-β mRNA expression, as well as HRG release into gastric fibroblast CM. IL-1β-stimulated HRG expression and release were also inhibited by celecoxib, and exogenous PGE2 restored this inhibitory effect, suggesting the activation of an IL-1β-COX-2-PGE2 pathway that culminates in the release of HRG from fibroblasts. HRG-α and HRG-β mRNA levels were significantly higher in gastric ulcer tissue than in normal gastric mucosa. HRG immunoreactivity was found in interstitial cells of the gastric ulcer bed and coexpressed with COX-2. These results suggest that HRG might be a new member of the growth factor family involved in the COX-2-dependent ulcer repair process.

Chagasic antibodies induce cardiac COX-2/iNOS mRNA expression with PGE2/NO production

2009 ◽  
Vol 134 (2) ◽  
pp. 212-223 ◽  
Author(s):  
Sabrina Ganzinelli ◽  
Enri Borda ◽  
Lilian Joensen ◽  
Leonor Sterin-Borda
Keyword(s):  
Mrna Expression ◽  
Inos Mrna ◽  
No Production ◽  
Cox 2

Antineoplastic 31-Norcycloartanones from Solanum cernuum Vell

2008 ◽  
Vol 63 (7-8) ◽  
pp. 507-514 ◽  
Author(s):  
Rogério Grando ◽  
Marcia A. Antônio ◽  
Carlos E. P. Araújo ◽  
Catarina Soares ◽  
Maria A. Medeiros ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Growth Inhibition ◽  
Tumour Cell ◽  
Ethanol Extract ◽  
Ethanol Administration ◽  
Lung Tumour ◽  
Tumour Cell Line ◽  
Antiulcer Activity ◽  
Total Growth ◽  
Ulcer Model

Triterpenoids with 31-norcycloartanone structure were isolated for the first time from the Solanum genus. Cycloeucalenone and 24-oxo-31-norcycloartanone were the main constituents of the dichloromethane extract of Solanum cernuum Vell. leaves [7% (w/w) and 1.47% (w/w)]. Both triterpenoids were tested against human tumour cell lines, and 24-oxo-31-norcycloartanone was significantly active and selective against the lung tumour cell line NCI-H460 with total growth inhibition at 1.10 μg/mL, growth inhibition 50 at 0.19 μg/mL and lethal concentration 50 at 8.43 μg/mL, while cycloeucalenone showed poor activity. A homologous series of alkanes (C25-C34), β-sitosterol, and the xanthophyll lutein were also identified. The antiulcer activity was assayed for the dichloromethane extract. In the gastric ulcer model induced by 95% ethanol, administration of 500, 1000 and 2000 mg/kg/po dichloromethane extract gave ulcer lesion indices of, respectively, 38.2, 61.0 and 81.9%, while carbenoxolone inhibited 88.9% at 200 mg/kg. In the gastric ulcer model induced by indomethacin the dichloromethane extract showed a small percentage of lesion inhibition. The ethanol extract was also analyzed and was mainly composed of glycoalkaloids, peptides and disaccharides.

scholarly journals Suppressive Effect of Quercetin on Nitric Oxide Production from Nasal Epithelial Cells In Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nachi Ebihara ◽  
Kana Takahashi ◽  
Haruka Takemura ◽  
Yuko Akanuma ◽  
Kazuhito Asano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Suppressive Effect ◽  
Inos Mrna ◽  
No Production ◽  
Minimum Concentration ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells

Nitric oxide (NO) is known to play pivotal roles as one of the final effector molecules in the development of allergic diseases, including allergic rhinitis (AR). Although quercetin has been reported to attenuate the clinical conditions of AR, its influence on NO production is not well defined. The present study aimed to examine the influence of quercetin on in vitro NO production from nasal epithelial cells after interleukin- (IL-) 4 stimulation. Human nasal epithelial cells (HNEpCs) at a concentration of 1 x 105 cells/ml were stimulated with 10.0 ng/ml of IL-4 in the presence and absence of quercetin. After 48 hours, the culture supernatants were collected and assayed for NO (NO2 and NO3) using the Griess method. The influences of quercetin on the transcription factor, STAT6, activation, and iNOS mRNA expression were also examined using ELISA and real-time quantitative RT-PCR, respectively. Addition of quercetin to cell cultures caused suppression of NO production from HNEpCs after IL-4 stimulation. The minimum concentration of quercetin that caused significant suppression was 1.0 nM. Treatment of cells with quercetin at more than 1.0 nM suppressed STAT6 activation and iNOS mRNA expression induced by IL-4 stimulation. The present results strongly suggested that quercetin favorably modified the clinical condition of AR through the suppression of NO production from nasal epithelial cells after IL-4 stimulation.

A vascular endothelial growth factor mimetic accelerates gastric ulcer healing in an iNOS-dependent manner

2008 ◽  
Vol 295 (2) ◽  
pp. G374-G381 ◽  
Author(s):  
Genevieve K. Dudar ◽  
Luca D. D'Andrea ◽  
Rossella Di Stasi ◽  
Carlo Pedone ◽  
John L. Wallace
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Gastric Ulcer ◽  
Growth Factor ◽  
Ulcer Healing ◽  
No Production ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Gastric Ulcer Healing ◽  
Cox 2 ◽  
Endothelial Growth Factor

Angiogenesis is crucial to all types of wound healing, including gastric ulcer healing. The most potent promoter of angiogenesis is vascular endothelial growth factor (VEGF). We hypothesized that a 15-amino acid peptide designed to mimic the angiogenic action of VEGF would accelerate gastric ulcer healing. Gastric ulcers were induced in mice by serosal application of acetic acid. Treatment with the VEGF mimetic accelerated gastric ulcer healing when administered orally or intraperitoneally, at a dose of 50 ng/kg or greater. Such healing was not observed when the reverse sequence pentadecapeptide or the full-length VEGF protein was administered. Contrary to our hypothesis, the VEGF mimetic did not significantly increase angiogenesis in the ulcerated stomach. The enhancement of ulcer healing by the VEGF mimetic occurred independently of cyclooxygenase-2 (COX-2) activity but was blocked by inhibitors of inducible nitric oxide synthase (iNOS). These results demonstrate that a VEGF mimetic is a potent stimulus for gastric ulcer healing, even when given orally. The effects of the mimetic were independent of stimulatory effects on angiogenesis and COX-2 activity but were dependent on iNOS-derived NO production.

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