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Spasmolytic effect of citral and extracts of Cymbopogon citratus on isolated rabbit ileum

Devi RC, Sim SM, Ismail R

J Smooth Muscle Res, 2011;47(5):143-56.
PMID: 22104376

Cymbopogon citratus, commonly known as lemongrass, has been shown to have antioxidant, antimicrobial and chemo-protective properties. Citral, a monoterpenoid, is the major constituent of C. citratus that gives off a lemony scent and is postulated to be responsible for most of its actions. In addition, C. citratus has been traditionally used to treat gastrointestinal discomforts, however, the scientific evidence for this is still lacking. Thus, the aim of the present study was to investigate the effect of the extracts of various parts of C. citratus (leaves, stems and roots) and citral on the visceral smooth muscle activity of rabbit ileum. The effect of the test substances were tested on the spontaneous contraction, acetylcholine (ACh)- and KCl-induced contractions. Citral at doses between 0.061 mM to 15.6 mM and the extract of leaves at doses between 0.001 mg/mL to 1 mg/mL significantly reduced the spontaneous, ACh- and KCl-induced ileal contractions. When the ileum was incubated in K(+)-rich-Ca(2+)-free Tyrode's solution, it showed only minute contractions. However, the strength of contraction was increased with the addition of increasing concentrations of CaCl(2). The presence of citral almost abolished the effect of adding CaCl(2), while the leaf extract shifted the calcium concentration-response curve to the right, suggesting a calcium antagonistic effect. These results were similar to that elicited by verapamil, a known calcium channel blocker. In addition, the spasmolytic effect of citral was observed to be reduced by the nitric oxide synthase inhibitor, L-NAME. In conclusion, citral and the leaf extract of C. citratus exhibited spasmolytic activity and it appeared that they may act as calcium antagonists. Furthermore, the relaxant effect of citral, but not that of the leaf extract may be mediated by nitric oxide suggesting the presence of other chemical components in the leaf extract other than citral.

Matched MeSH terms: Nitric Oxide/physiology
Cloning of nitric oxide associated 1 (NOA1) transcript from oil palm (Elaeis guineensis) and its expression during Ganoderma infection

Kwan YM, Meon S, Ho CL, Wong MY

J Plant Physiol, 2015 Feb 01;174:131-6.
PMID: 25462975 DOI: 10.1016/j.jplph.2014.10.003

Nitric oxide associated 1 (NOA1) protein is implicated in plant disease resistance and nitric oxide (NO) biosynthesis. A full-length cDNA encoding of NOA1 protein from oil palm (Elaeis guineensis) was isolated and designated as EgNOA1. Sequence analysis suggested that EgNOA1 was a circular permutated GTPase with high similarity to the bacterial YqeH protein of the YawG/YlqF family. The gene expression of EgNOA1 and NO production in oil palm root tissues treated with Ganoderma boninense, the causal agent of basal stem rot (BSR) disease were profiled to investigate the involvement of EgNOA1 during fungal infection and association with NO biosynthesis. Real-time PCR (qPCR) analysis revealed that the transcript abundance of EgNOA1 in root tissues was increased by G. boninense treatment. NO burst in Ganoderma-treated root tissue was detected using Griess reagent, in advance of the up-regulation of the EgNOA1 transcript. This indicates that NO production was independent of EgNOA1. However, the induced expression of EgNOA1 in Ganoderma-treated root tissues implies that it might be involved in plant defense responses against pathogen infection.

Matched MeSH terms: Nitric Oxide/metabolism*
Decreased glutamine synthetase, increased citrulline-nitric oxide cycle activities, and oxidative stress in different regions of brain in epilepsy rat model

Swamy M, Yusof WR, Sirajudeen KN, Mustapha Z, Govindasamy C

J Physiol Biochem, 2011 Mar;67(1):105-13.
PMID: 20960085 DOI: 10.1007/s13105-010-0054-2

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.

Matched MeSH terms: Nitric Oxide/biosynthesis; Nitric Oxide/metabolism*; Nitric Oxide Synthase/metabolism
The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice

Zakaria ZA, Sulaiman MR, Somchit MN, Jais AM, Ali DI

J Pharm Pharm Sci, 2005;8(2):199-206.
PMID: 16124931

To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test.

Matched MeSH terms: Nitric Oxide/antagonists & inhibitors; Nitric Oxide/physiology
α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents

Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, et al.

J Pharm Sci, 2019 11;108(11):3592-3598.
PMID: 31288036 DOI: 10.1016/j.xphs.2019.07.002

Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.

Matched MeSH terms: Nitric Oxide/administration & dosage
Fulltext Pharmacokinetic evaluation, molecular docking and in vitro biological evaluation of 1, 3, 4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

Khanam R, Hejazi II, Shahabuddin S, Bhat AR, Athar F

J Pharm Anal, 2019 Apr;9(2):133-141.
PMID: 31011470 DOI: 10.1016/j.jpha.2018.12.002

1, 3, 4-Oxadiazole derivatives (4a-5f) were previously synthesized to investigate their anticancer properties. However, studies relating to their antioxidant potential and signal transducer and activator of transcription (STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives (4a-5f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical (DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5e (-9.91kcal/mol). Through virtual screening, compound 5e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5e decreased the activation of STAT3 as observed with Western blot. In brief, compound 5e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

Matched MeSH terms: Nitric Oxide
Effect of exogenous nitric oxide on murine immune response induced by Aggregatibacter actinomycetemcomitans lipopolysaccharide

Sosroseno W, Bird PS, Seymour GJ

J Periodontal Res, 2009 Aug;44(4):529-36.
PMID: 18973550 DOI: 10.1111/j.1600-0765.2008.01157.x

Elevated nitric oxide (NO) has been associated with destructive periodontal disease. The aim of the present study was to test the hypothesis that exogenous NO may inhibit a protective immune response to Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) in a murine model.

Matched MeSH terms: Nitric Oxide/pharmacology*; Nitric Oxide Donors/pharmacology; Nitric Oxide Synthase Type II/analysis; Nitric Oxide Synthase Type II/antagonists & inhibitors
Effect of L-N6-(1-iminoethyl)-lysine, an inducible nitric oxide synthase inhibitor, on murine immune response induced by Actinobacillus actinomycetemcomitans lipopolysaccharide

Sosroseno W, Musa M, Ravichandran M, Fikri Ibrahim M, Bird PS, Seymour GJ

J Periodontal Res, 2007 Apr;42(2):124-30.
PMID: 17305870

Inducible nitric oxide synthase (iNOS) activity is known to regulate the immune response. The present study was carried out to determine the effect of L-N6-(1-iminoethyl)-lysine (L-NIL), an iNOS inhibitor, on the induction of immune response to Actinobacillus actinomycetemcomitans lipopolysaccharide in mice.

Matched MeSH terms: Nitric Oxide/blood; Nitric Oxide Synthase Type II/antagonists & inhibitors*; Nitric Oxide Synthase Type II/blood; Nitric Oxide Synthase Type II/metabolism
Fulltext Survival and associated risk factors for mortality among infants with persistent pulmonary hypertension of the newborn in Malaysia

Mat Bah MN, Tan RYH, Razak H, Sapian MH, Abdullah N, Alias EY

J Perinatol, 2021 04;41(4):786-793.
PMID: 33589728 DOI: 10.1038/s41372-021-00962-6

OBJECTIVE: This study aims to determine the immediate outcome of persistent pulmonary hypertension of the newborn (PPHN) and risk factors for mortality in the era of inhaled nitric oxide (iNO).
STUDY DESIGN: This observational cross-sectional study includes 195 confirmed PPHN with a gestational age of ≥34 weeks without congenital heart disease. Multivariable logistic regression was used to identify risk factors for mortality.
RESULTS: The mortality rate was 16.4%, with the highest mortality with pulmonary hypoplasia. Of 195, 65% received iNO; 18% were iNO non-responders with the majority having pulmonary hypoplasia. Independent risk factors for mortality were the presence of reversal of flow at the descending aorta, pulmonary hypoplasia, APGAR scores ≤ 5 at 5 min, and idiopathic PPHN with an adjusted odds ratio of 15.9, 7.5, 6.7, and 6.4, respectively.
CONCLUSIONS: Despite the usage of iNO, mortality due to PPHN remains high and is related to etiology and cardiac function.

Matched MeSH terms: Nitric Oxide/therapeutic use
Effect of acute exercise on the levels of salivary cortisol, tumor necrosis factor-alpha and nitric oxide

Rahman ZA, Abdullah N, Singh R, Sosroseno W

J Oral Sci, 2010 Mar;52(1):133-6.
PMID: 20339244

The aim of the present study was to assess the levels of salivary cortisol, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) before, during and after acute exercise. Acute exercise was induced using a standard treadmill test with Bruce protocol in ten physically active male participants. Unstimulated saliva was collected before, during and after exercise. The levels of salivary cortisol and TNF-alpha were assessed by enzyme immunoassays. Salivary NO was determined by the Griess reagent. The results showed that both salivary cortisol and TNF-alpha increased and peaked at 14 min during exercise and then decreased. The levels of NO were increased up to 1 h after exercise and subsequently lowered after 24 h. The results of the present study suggest that acute exercise may induce high levels of salivary cortisol, TNF-alpha and NO.

Matched MeSH terms: Nitric Oxide/analysis; Nitric Oxide/biosynthesis*
Cytotoxicity and inhibition of nitric oxide in lipopolysaccharide induced mammalian cell lines by aqueous extracts of brown seaweed

Jaswir I, Monsur HA, Simsek S, Amid A, Alam Z, bin Salleh MN, et al.

J Oleo Sci, 2014;63(8):787-94.
PMID: 25007746

Aqueous extracts obtained from five Malaysian brown seaweeds, Sargassum duplicatum, Sargassum binderi, Sargassum fulvellum, Padina australis, and Turbinaria turbinata, were investigated for their abilities to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cell lines as well as to determine their chemical composition. The percentage yield of extracts varied among species, with P. australis having the lowest yield and T. turbinata having the highest yield. The chemical compositions of the extracts showed that the percentage of sulfate ions as well as uronic acid and total sugar content varied significantly. All extracts contained high fucose and inhibited NO secretion in a dose-dependent manner. Extracts of P. australis and T. turbinata dosed at 200 μg/mL were able to inhibit NO secretion by > 75%. Furthermore, cytotoxicity assays revealed that some extracts were moderately toxic, while others were not. Based on these results, brown seaweed of Malaysian origin should be investigated for the production of additional anti-inflammatory compounds.

Matched MeSH terms: Nitric Oxide/secretion*
Fulltext CNDP1, NOS3, and MnSOD Polymorphisms as Risk Factors for Diabetic Nephropathy among Type 2 Diabetic Patients in Malaysia

Yahya MJ, Ismail PB, Nordin NB, Akim ABM, Binti Md Yusuf WS, Adam NLB, et al.

J Nutr Metab, 2019;2019:8736215.
PMID: 30719346 DOI: 10.1155/2019/8736215

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880 and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for the D18S880 of CNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the least p value. The rs2346061 of CNDP1 was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76-3.20) and fitted best the multiplicative model, while D18S880 was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48-4.10), Chinese with OR = 2.26 and 95% CI = (1.34-3.83), and Indians with OR = 1.77 and 95% CI = (1.18-2.65) in the genotypic multiplicative model. The best mode of inheritance for both MnSOD and NOS3 was the additive model. For MnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53-14.94), Indians had OR = 2.4 and 95% CI = (0.69-2.84), and Malays had OR = 2.16 and 95% CI = (0.54-8.65), while for NOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52-17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36-35.03) and the Malays with OR = 2.89 and 95% CI = (0.29-28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.

Matched MeSH terms: Nitric Oxide Synthase Type III
Fulltext Mesenchymal stem cells exert anti-proliferative effect on lipopolysaccharide-stimulated BV2 microglia by reducing tumour necrosis factor-α levels

Jose S, Tan SW, Ooi YY, Ramasamy R, Vidyadaran S

J Neuroinflammation, 2014;11:149.
PMID: 25182840 DOI: 10.1186/s12974-014-0149-8

Progression of neurodegenerative diseases occurs when microglia, upon persistent activation, perpetuate a cycle of damage in the central nervous system. Use of mesenchymal stem cells (MSC) has been suggested as an approach to manage microglia activation based on their immunomodulatory functions. In the present study, we describe the mechanism through which bone marrow-derived MSC modulate the proliferative responses of lipopolysaccharide-stimulated BV2 microglia.

Matched MeSH terms: Nitric Oxide/metabolism
Chisomicines A-C, limonoids from Chisocheton ceramicus

Najmuldeen IA, Hadi AH, Awang K, Mohamad K, Ketuly KA, Mukhtar MR, et al.

J Nat Prod, 2011 May 27;74(5):1313-7.
PMID: 21428417 DOI: 10.1021/np200013g

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.

Matched MeSH terms: Nitric Oxide/antagonists & inhibitors
Eucophylline, a Tetracyclic Vinylquinoline Alkaloid from Leuconotis eugenifolius

Deguchi J, Shoji T, Nugroho AE, Hirasawa Y, Hosoya T, Shirota O, et al.

J Nat Prod, 2010 Oct 22;73(10):1727-9.
PMID: 20836516 DOI: 10.1021/np100458b

Eucophylline (1), a new tetracyclic vinylquinoline alkaloid, was isolated from the bark of Leuconotis eugenifolius together with leucophyllidine (2). The structure and absolute configuration of 1 were elucidated on the basis of 2D NMR correlations and simulated CD analysis. Leucophyllidine (2) showed iNOS inhibitory activity and decreased the iNOS protein expression dose-dependently.

Matched MeSH terms: Nitric Oxide Synthase Type II/drug effects; Nitric Oxide Synthase Type II/metabolism
Modulation of the Nitrergic Pathway via Activation of PPAR-γ Contributes to the Neuroprotective Effect of Pioglitazone Against Streptozotocin-Induced Memory Dysfunction

Prakash A, Kumar A, Ming LC, Mani V, Majeed AB

J Mol Neurosci, 2015 Jul;56(3):739-50.
PMID: 25854775 DOI: 10.1007/s12031-015-0508-7

Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired memory function and oxidative damage. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through modulating nitric oxide synthase. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. The present study was designed to investigate the possible nitric oxide mechanism in the protective effect of pioglitazone against streptozotocin (STZ)-induced memory dysfunction. Wistar rats were intracerebroventricularly (ICV) injected with STZ. Then rats were treated with pioglitazone, NO modulators [L-arginine and nitro-L-arginine methyl ester (L-NAME)] for 21 days. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and mito-oxidative parameters, TNF-α, IL-6, and caspase-3 activity were measured. STZ-treated rats showed a memory deficit and significantly increased in mito-oxidative damage and inflammatory mediators and apoptosis in the hippocampus. Chronic treatment of pioglitazone significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers, and apoptosis in STZ-treated rats. However, L-arginine pretreatment with lower dose of pioglitazone has not produced any protective effect as compared to per se. Furthermore, pretreatment of L-NAME significantly potentiated its protective effect, which indicates the involvement of nitric oxide for activation of PPAR-γ action. These results demonstrate that pioglitazone offers protection against STZ-induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, and anti-apoptotic action mediating nitric oxide pathways and, therefore, could have a therapeutic potential in AD.

Matched MeSH terms: Nitric Oxide/metabolism*
Antihypertensive and cardiovascular effects of catechin-rich oil palm (Elaeis guineensis) leaf extract in nitric oxide-deficient rats

Jaffri JM, Mohamed S, Rohimi N, Ahmad IN, Noordin MM, Manap YA

J Med Food, 2011 Jul-Aug;14(7-8):775-83.
PMID: 21631357 DOI: 10.1089/jmf.2010.1170

Oil palm (Elaeis guineensis) leaf extract (OPLE) possesses good ex vivo vasodilation and antioxidant properties. This study evaluated the catechin-rich OPLE antioxidant, antihypertensive, and cardiovascular effects in normal and nitric oxide (NO)-deficient hypertensive rats. OPLE was administered orally (500 mg/kg of body weight/day) to normotensive Wistar rats and N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced NO-deficient hypertensive rats. OPLE significantly (P

Matched MeSH terms: Nitric Oxide/deficiency*
Assessment of Polygonum odoratum Lour. Leaf Extract on Rat's Ileum Contraction and the Mechanisms Involved

Duangjai A, Parseatsook K, Sajjapong W, Saokaew S

J Med Food, 2020 Nov;23(11):1169-1175.
PMID: 32976072 DOI: 10.1089/jmf.2020.4769

Vietnamese coriander (Polygonum odoratum Lour.) is a plant native to northern Thailand. The biological activities of P. odoratum Lour. extract (POE) include antibacterial, antiviral, and expectorant. However, the effect of POE on intestinal smooth muscle motility is unclear. The aim of this study was to evaluate the relaxant effects of POE on isolated rat ileum. Propranolol (1 μM), calcium chloride (1-20 mM), and Nω-nitro-l-arginine methylester (l-NAME, 100 μM) were used to investigate the mechanisms of action. The results showed that POE (0.01-5 mg/mL) reduced KCl-induced contraction. In addition, POE (1 mg/mL) reduced the contraction by propranolol and l-NAME and attenuated CaCl2-induced contractions. Our results indicate that the relaxation effect of POE on ileum contractions seems to involve nitric oxide and β-adrenergic pathways, and blockade of calcium influx. These findings provide a pharmacological basis for the traditional use of POE to treat gastrointestinal disorders such as irritable bowel syndrome or diarrhea.

Matched MeSH terms: Nitric Oxide/metabolism
Mechanisms of Action of Uncaria rhynchophylla Ethanolic Extract for Its Vasodilatory Effects

Loh YC, Ch'ng YS, Tan CS, Ahmad M, Asmawi MZ, Yam MF

J Med Food, 2017 Sep;20(9):895-911.
PMID: 28771084 DOI: 10.1089/jmf.2016.3804

Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.

Matched MeSH terms: Nitric Oxide/metabolism
Fulltext The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Abbas MA, Suppian R

J Infect Dev Ctries, 2019 11 30;13(11):1057-1061.
PMID: 32087079 DOI: 10.3855/jidc.11331

INTRODUCTION: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4).
METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.
RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.
CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide Synthase Type II/metabolism

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