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Fulltext Betulinic acid‑induced expression of nicotinamide adenine dinucleotide phosphate‑diaphorase in the immune organs of mice: A possible role of nitric oxide in immunomodulation

Pang KL, Vijayaraghavan K, Al Sayed B, Seyed MA

Mol Med Rep, 2018 Feb;17(2):3035-3041.
PMID: 29257292 DOI: 10.3892/mmr.2017.8262

The aim of the present study was to investigate the effects of betulinic acid (BetA) on the expression and distribution pattern of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‑d), an indirect indicator of nitric oxide (NO) synthase in the thymus and spleen of mice. Mice were randomly assigned to four main groups (n=48 per group): Experimental group (BetA), positive control group (goniothalamin), vehicle control group (dimethyl sulfoxide) and control group (without vehicle). Each group was further divided into three equal subgroups according to the treatment length (4, 8 and 12 days). BetA treatment induced the expression of NADPH‑d activity in the thymus and spleen without any significant changes in the morphology of the organs. Furthermore, the expression pattern of NADPH‑d in BetA‑treated animals was significantly increased compared with that in the control animals. NADPH‑d expression in the thymus and spleen suggests that NO signaling may be a potential mechanism underlying the BetA‑induced immunomodulation in these organs. These findings are of direct clinical relevance and may contribute to the further development of BetA as a therapeutic drug.

Matched MeSH terms: Nitric Oxide/immunology*
Effects of macrophage colony-stimulating factor on microglial responses to lipopolysaccharide and beta amyloid

Vidyadaran S, Ooi YY, Subramaiam H, Badiei A, Abdullah M, Ramasamy R, et al.

Cell Immunol, 2009;259(1):105-10.
PMID: 19577228 DOI: 10.1016/j.cellimm.2009.06.005

A challenge for studies involving microglia cultures is obtaining sufficient cells for downstream experiments. Macrophage colony-stimulating factor (M-CSF) has been used to improve yield of microglia in culture. However, the effects of M-CSF on activation profiles of microglia cultures are still unclear. Microglia activation is characterised by upregulation of co-stimulatory molecules and an inflammatory phenotype. The aim of this study is to demonstrate whether M-CSF supplementation alters microglial responses in resting and activated conditions. Microglia derived from mixed glia cultures and the BV-2 microglia cell line were cultivated with/without M-CSF and activated with lipopolysaccharide (LPS) and beta amyloid (Abeta). We show M-CSF expands primary microglia without affecting microglial responses to LPS and Abeta, as shown by the comparable expression of MHC class II and CD40 to microglia grown without this growth factor. M-CSF supplementation in BV-2 cells had no effect on nitric oxide (NO) production. Therefore, M-CSF can be considered for improving microglia yield in culture without introducing activation artefacts.

Matched MeSH terms: Nitric Oxide/biosynthesis
Expression of beta-catenin, COX-2 and iNOS in colorectal cancer: relevance of COX-2 adn iNOS inhibitors for treatment in Malaysia

Hong SK, Gul YA, Ithnin H, Talib A, Seow HF

Asian J Surg, 2004 Jan;27(1):10-7.
PMID: 14719508

BACKGROUND: Promising new pharmacological agents and gene therapy targeting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) could modulate treatment of colorectal cancer in the future. The aim of this study was to elucidate the expression fo beta-catenin and teh presence of COX-2 and iNOS in colorectal cancer specimens in Malaysia. This is a useful prelude to future studies investigating interventions directed towards COX-2 adn iNOS.
METHODS: A cross-section study using retrospective data over a 2-year period (1999-2000) involved 101 archival, formalin-fixed, paraffin-embedded tissue samples of colorectal cancers that were surgically resected in a tertiary referral.
RESULTS: COX-2 production was detected in adjacent normal tissue in 34 sample (33.7%) and in tumour tissue in 60 samples (59.4%). More tumours expressed iNOS (82/101, 81.2%) than COX-2. No iNOS expression was detected in adjacent normal tissue. Intense beta-catenin immunoreactivity at the cell-to-cell border. Poorly differentiated tumours had significantly lower total beta-catenin (p = 0.009) and COX-2 scores (p = 0.031). No significant relationships were established between pathological stage and beta-catenin, COX-2 and iNOS scores.
CONCLUSIONS: the accumulation of beta-catenin does not seem to be sufficient to activate pathways that lead to increased COX-2 and iNOS expression. A high proportion of colorectal cancers were found to express COX-2 and a significant number produced iNOS, suggesting that their inhibitors may be potentially useful as chemotherapeutic agents in the management of colorectal cancer.

Matched MeSH terms: Nitric Oxide Synthase/antagonists & inhibitors; Nitric Oxide Synthase/metabolism*; Nitric Oxide Synthase Type II
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line)

Fonseka M, Ramasamy R, Tan BC, Seow HF

Cell Biol Int, 2012 Sep;36(9):793-801.
PMID: 22335239 DOI: 10.1042/CBI20110595

hUCB-MSC (human umbilical cord blood-derived mesenchymal stem cells) offer an attractive alternative to bone marrow-derived MSC for cell-based therapy by being less invasive a source of biological material. We have evaluated the effect of hUCB-MSC on the proliferation of K562 (an erythromyeloblastoid cell line) and the cytokine secretion pattern of hUCB-MSC. Co-culturing of hUCB-MSC and K562 resulted in inhibition of proliferation of K562 in a dose-dependent manner. However, the anti-proliferative effect was reduced in transwells, suggesting the importance of direct cell-to-cell contact. hUCB-MSC inhibited proliferation of K562, arresting them in the G0 /G1 phase. NO (nitric oxide) was not involved in the hUCB-MSC-mediated tumour suppression. The presence of IL-6 (interleukin 6) and IL-8 were obvious in the hUCB-MSC conditioned media, but no significant increase was found in 29 other cytokines. Th1 cytokines, IFNα (interferon α), Th2 cytokine IL-4 and Th17 cytokine, IL-17 were not secreted by hUCB-MSC. There was an increase in the number of hUCB-MSC expressing the latent membrane-bound form of TGFβ1 co-cultured with K562. The anti-proliferative effect of hUCB-MSC was due to arrest of the growth of K562 in the G0 /G1 phase. The mechanisms underlying increased IL-6 and IL-8 secretion and LAP (latency-associated peptide; TGFβ1) by hUCB-MSC remains unknown.

Matched MeSH terms: Nitric Oxide
Fulltext Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase in Normal and Preeclamptic Placentae

Khaing A, Swe AT, Aung CL, Thwin MM, Sein MT

Rev Bras Ginecol Obstet, 2022 Feb;44(2):125-132.
PMID: 35213910 DOI: 10.1055/s-0042-1742317

OBJECTIVE: To investigate the expression of endothelin-1 (ET-1) and endothelial nitric oxide (NO) synthase (eNOS) in normal and preeclamptic (PE) placentae.
METHODS: The present cross-sectional analytical study was performed in normal and PE primigravidae (n = 10 in each group) who were admitted to the North Okkalapa General and Teaching Hospital from February 2019 to February 2020. Serum samples were collected immediately before delivery, and placental tissues were collected immediately after emergency or elective cesarean section. The expression of placental eNOS was measured by western blot, and the levels of ET-1 in placental tissue homogenates and in the serum were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS: The PE group had significantly higher serum levels of ET-1 (median: 116.56 pg/mL; IQR: 89.14-159.62 pg/mL) than the normal group (median: 60.02 pg/mL; IQR: 50.89-94.37 pg/mL) (p

Matched MeSH terms: Nitric Oxide Synthase Type III
In vitro antioxidant activity potential of lantadene A, a pentacyclic triterpenoid of Lantana plants

Grace-Lynn C, Darah I, Chen Y, Latha LY, Jothy SL, Sasidharan S

Molecules, 2012 Sep 19;17(9):11185-98.
PMID: 22992785

Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), hydroxyl radical (OH•), nitric oxide radical (NO•), superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.

Matched MeSH terms: Nitric Oxide/metabolism
Fulltext Antioxidant Activity and Hepatoprotective Potential of Polyalthia longifolia and Cassia spectabilis Leaves against Paracetamol-Induced Liver Injury

Jothy SL, Aziz A, Chen Y, Sasidharan S

Evid Based Complement Alternat Med, 2012;2012:561284.
PMID: 23243455 DOI: 10.1155/2012/561284

In the present study, in vitro antioxidant, free radical scavenging capacity, and hepatoprotective activity of methanol extracts from Polyalthia longifolia and Cassia spectabilis were evaluated using established in vitro models such as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH(•)), hydroxyl radical (OH(•)), nitric oxide radical (NO(•)) scavenging, metal chelating, and antilipidperoxidation activities. Interestingly, all the extracts showed considerable in vitro antioxidant and free radical scavenging activities in a dose-dependent manner when compared to the standard antioxidant which verified the presence of strong antioxidant compound in leaf extracts tested. Phenolic and flavonoid content of these extracts is significantly correlated with antioxidant capacity. Since P. longifolia extract was exhibited better in vitro antioxidant activities, it was subjected for in vivo hepatoprotective activity in paracetamol-intoxicated mice. Therapy of P. longifolia showed the liver protective effect on biochemical and histopathological alterations. Moreover, histological studies also supported the biochemical finding, that is, the maximum improvement in the histoarchitecture of the liver. Results revealed that P. longifolia leaf extract could protect the liver against paracetamol-induced oxidative damage by possibly increasing the antioxidant protection mechanism in mice. Our findings indicated that P. longifolia and C. spectabilis have potential as good sources of natural antioxidant/antiaging compounds.

Matched MeSH terms: Nitric Oxide
Fulltext Neurodevelopmental outcome of newborns with persistent pulmonary hypertension

Rohana J, Boo NY, Chandran V, Sarvananthan R

Malays J Med Sci, 2011 Oct;18(4):58-62.
PMID: 22589673 MyJurnal

Developmental disabilities have been reported in infants with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (INO) or intravenous magnesium sulphate (MgSO(4)) and/or extracorporeal membrane oxygenation. This paper reports the rate of developmental disabilities at 2 years of age in a cohort of survivors of PPHN treated with INO, MgSO(4), or both during the neonatal period.

Matched MeSH terms: Nitric Oxide
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
Fulltext Mechanism(s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura

Zakaria ZA, Balan T, Azemi AK, Omar MH, Mohtarrudin N, Ahmad Z, et al.

BMC Complement Altern Med, 2016 Feb 24;16:78.
PMID: 26912079 DOI: 10.1186/s12906-016-1041-0

BACKGROUND: Muntingia calabura L. (family Muntingiaceae), commonly known as Jamaican cherry or kerukup siam in Malaysia, is used traditionally to treat various ailments. The aim of this study is to elucidate the possible underlying gastroprotective mechanisms of ethyl acetate fraction (EAF) of Muntingia calabura methanolic leaves extract (MEMC).
METHODS: MEMC and its fractions were subjected to HPLC analysis to identify and quantify the presence of its phyto-constituents. The mechanism of gastroptotection of EAF was further investigated using pylorus ligation-induced gastric lesion rat model (100, 250, and 500 mg/kg). Macroscopic analysis of the stomach, evaluation of gastric content parameters such as volume, pH, free and total acidity, protein estimation, and quantification of mucus were carried out. The participation of nitric oxide (NO) and sulfhydryl (SH) compounds was evaluated and the superoxide dismutase (SOD), gluthathione (GSH), catalase (CAT), malondialdehyde (MDA), prostaglandin E2 (PGE2) and NO level in the ethanol induced stomach tissue homogenate was determined.
RESULTS: HPLC analysis confirmed the presence of quercetin and gallic acid in EAF. In pylorus-ligation model, EAF significantly (p <0.001) prevent gastric lesion formation. Volume of gastric content and total protein content reduced significantly (p

Matched MeSH terms: Nitric Oxide/metabolism
Fulltext Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

Sani MH, Zakaria ZA, Balan T, Teh LK, Salleh MZ

Evid Based Complement Alternat Med, 2012;2012:890361.
PMID: 22611437 DOI: 10.1155/2012/890361

Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

Matched MeSH terms: Nitric Oxide
Fulltext The Efficacy of Processing Strategies on the Gastroprotective Potentiality of Chenopodium quinoa Seeds

Mariod AA, Salama SM

ScientificWorldJournal, 2020;2020:6326452.
PMID: 32549800 DOI: 10.1155/2020/6326452

The current study has been conducted to evaluate the effect of different processing techniques on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and the gastroprotective potential of Chenopodium quinoa red seeds in acute gastric injury induced by absolute ethanol in rats. Seven groups of female Sprague Dawley rats were assigned to normal and absolute ethanol (absolute EtOH) groups, given distilled water, reference control omeprazole (OMP, 20 mg/kg), pressure-cooked quinoa seeds (QP, 200 mg/kg), first stage-germinated quinoa seeds (QG, 200 mg/kg), Lactobacillus plantarum bacteria-fermented quinoa seeds (QB, 200 mg/kg), and Rhizopus oligosporus fungus-fermented quinoa seeds (QF, 200 mg/kg). One hour after treatment, all groups were given absolute ethanol, except for the normal control rats. All animals were sacrificed after an additional hour, and the stomach tissues were examined for histopathology of hematoxylin and eosin staining, immunohistochemistry of cyclooxygenase 2 (COX-2), and nitric oxide synthase (iNOS). Stomach homogenates were evaluated for oxidative stress parameters and prostaglandin E2 (PGE2). Gene expression was performed for gastric tumor necrosis factor alpha (TNF-α) and nuclear factor kappa of B cells (NF-kB). QB and QG recorded the highest DPPH scavengers compared to QF and QP. The gastroprotective potential of QB was comparable to that of OMP, followed by QF, then QG, and QP as confirmed by the histopathology, immunohistochemistry, and gene expression assessments. In conclusion, differently processed red quinoa seeds revealed variable antioxidant capacity and gastroprotective potential, while the bacterial fermented seeds (QB) showed the highest potential compared to the other processing techniques. These results might offer promising new therapy in the treatment of acute gastric injury.

Matched MeSH terms: Nitric Oxide Synthase Type II/metabolism
Removal of NOx and CO from a burner system

Jaafar MN, Ishak MS, Saharin S

Environ Sci Technol, 2010 Apr 15;44(8):3111-5.
PMID: 20345095 DOI: 10.1021/es903606y

This paper presents the development of an emissions-controlling technique for oil burners aimed especially to reduce oxides of nitrogen (NOx). Another emission of interest is carbon monoxide (CO). In this research, a liquid fuel burner is used. In the first part, five different radial air swirler blade angles, 30 degrees , 40 degrees , 45 degrees , 50 degrees , and 60 degrees , respectively, have been investigated using a combustor with 163 mm inside diameter and 280 mm length. Tests were conducted using kerosene as fuel. Fuel was injected at the back plate of the swirler outlet. The swirler blade angles and equivalence ratios were varied. A NOx reduction of more than 28% and CO emissions reduction of more than 40% were achieved for blade angle of 60 degrees compared to the 30 degrees blade angle. The second part of this paper presents the insertion of an orifice plate at the exit plane of the air swirler outlet. Three different orifice plate diameters of 35, 40, and 45 mm were used with a 45 degrees radial air swirler vane angle. The fuel flow rates and orifice plate's sizes were varied. NOx reduction of more than 30% and CO emissions reduction of more than 25% were obtained using the 25 mm diameter orifice plate compared to the test configuration without the orifice plate. The last part of this paper presents tests conducted using the air-staging method. An industrial oil burner system was investigated using the air staging method in order to reduce emission, especially NOx. Emissions reduction of 30% and 16.7% were obtained for NOx and CO emissions, respectively, when using air staging compared to the non-air-staging tests.

Matched MeSH terms: Nitric Oxide/isolation & purification*
Nitric oxide increases Pb tolerance by lowering Pb uptake and translocation as well as phytohormonal changes in Cowpea (Vigna Unguiculata (L.) Walp.)

Sadeghipour O

Sains Malaysiana, 2017;46:189-195.

Lead (Pb) is one of the most abundant toxic heavy metals which adversely affected growth and yield of crop plants. Nitric oxide (NO), an endogenous signaling molecule, has been suggested to be involved in defense responses to biotic and abiotic stresses in plants. The present study was done to induce Pb tolerance in cowpea plants by exogenous NO application using two levels of Pb, 0 and 200 mg Pb (NO3)2 kg-1 soil and three NO levels, 0, 0.5 and 1 mM sodium nitroprusside (SNP), as NO donor. The results showed that Pb treatment caused a significant increase in Pb concentration in all plant parts. Roots had higher levels of Pb than the stems, leaves and seeds. Furthermore, lead toxicity reduced auxin (IAA), cytokinin and gibberellic acid (GA3) content but increased abscisic acid (ABA) level. Moreover Pb stress decreased stomatal conductance, leaf area and consequently seed yield of cowpea. Exogenous application of NO at 0.5 mM noticeably alleviated the lead toxicity by improving the leaf area, stomatal conductance and seed yield. NO increased Pb tolerance by lowering Pb uptake and translocation, enhancing the promoting phytohormone (IAA, cytokinin and GA3) level and reducing ABA content.

Matched MeSH terms: Nitric Oxide; Nitric Oxide Donors
Synthesized 2-Trifluoromethylquinazolines and Quinazolinones Protect BV2 and N2a Cells against LPS- and H2O2-induced Cytotoxicity

Nallathamby N, Phan CW, Sova M, Saso L, Sabaratnam V

Med Chem, 2021;17(6):623-629.
PMID: 31849289 DOI: 10.2174/1573406416666191218095635

BACKGROUND: Microglia are associated with neuroinflammation, which play a key role in the pathogenesis of neurodegenerative diseases. It has been reported that some quinazolines and quinazolinones possess anti-inflammatory properties. However, the pharmacological properties of certain quinazoline derivatives are still unknown.
OBJECTIVE: The antioxidant, cytotoxic, and protective effects of a series of synthesized 2- trifluoromethylquinazolines (2, 4, and 5) and quinazolinones (6-8) in lipopolysaccharide (LPS)- murine microglia (BV2) and hydrogen peroxide (H2O2)-mouse neuroblastoma-2a (N2a) cells were investigated.
METHOD: The antioxidant activity of synthesized compounds was evaluated with ABTS and DPPH assays. The cytotoxic activities were determined by MTS assay in BV2 and N2a cells. The production of nitric oxide (NO) in LPS-induced BV2 microglia cells was quantified.
RESULTS: The highest ABTS and DPPH scavenging activities were observed for compound 8 with 87.7% of ABTS scavenge percentage and 54.2% DPPH inhibition. All compounds were noncytotoxic in BV2 and N2a cells at 5 and 50 μg/mL. The compounds which showed the highest protective effects in LPS-induced BV2 and H2O2-induced N2a cells were 5 and 7. All tested compounds, except 4, also reduced NO production at concentrations of 50 μg/mL. The quinazolinone series 6-8 exhibited the highest percentage of NO reduction, ranging from 38 to 60%. Compounds 5 and 8 possess balanced antioxidant and protective properties against LPS- and H2O2-induced cell death, thus showing great potential to be developed into anti-inflammatory and neuroprotective agents.
CONCLUSION: Compounds 5 and 7 were able to protect the BV2 and N2a cells against LPS and H2O2 toxicity, respectively, at a low concentration (5 μg/mL). Compounds 6-8 showed potent reduction of NO production in BV2 cells.

Matched MeSH terms: Nitric Oxide/biosynthesis
Lipids in an Ethyl Acetate Fraction of Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Reduce Nitric Oxide Production in BV2 Cells via NRF2 and NF-κB Pathways

Nallathamby N, Malek SNA, Vidyadaran S, Phan CW, Sabaratnam V

Int J Med Mushrooms, 2020;22(12):1215-1223.
PMID: 33463938 DOI: 10.1615/IntJMedMushrooms.2020037001

Cordyceps militaris is known for its curative properties. The present study was undertaken to evaluate the reduction of nitric oxide production by BV2 cells by the bioactive fraction of stroma powder of C. militaris, and to deduce the potential chemical components and pathways that may be responsible. The CE2 fraction from ethyl acetate extract did not exert any cytotoxic effects toward the BV2 cells at concentrations 0.1 to 100 μg/mL. The CE2 fraction also showed a significant (p < 0.05) reduction in nitric oxide production at 1-100 μg/mL. At 10 μg/mL, the CE2 fraction attenuated 85% of the NO production in BV2 cells. Further, the CE2 fraction (10 μg/mL) downregulated inflammatory genes, iNOS and COX-2, and upregulated anti-inflammatory genes, HO-1 and NQO-1. The CE2 fraction reduced NO production via activation of NRF2 and NF-κB transcriptions. The chemical constituents of the bioactive CE2 fraction were identified via GCMS. Eleven lipid components were identified including fatty acids, fatty acid esters, and sterols.

Matched MeSH terms: Nitric Oxide/metabolism*
Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: Possible mechanisms

Pandurangan AK, Mohebali N, Mohd Esa N, Looi CY, Ismail S, Saadatdoust Z

Int Immunopharmacol, 2015 Oct;28(2):1034-43.
PMID: 26319951 DOI: 10.1016/j.intimp.2015.08.019

Inflammatory bowel diseases (IBD) encompass at least two forms of intestinal inflammation: Crohn's disease and ulcerative colitis (UC). Both conditions are chronic and inflammatory disorders in the gastrointestinal tract, with an increasing prevalence being associated with the industrialization of nations and in developing countries. Patients with these disorders are 10 to 20 times more likely to develop cancer of the colon. The aim of this study was to characterize the effects of a naturally occurring polyphenol, gallic acid (GA), in an experimental murine model of UC. A significant blunting of weight loss and clinical symptoms was observed in dextran sodium sulfate (DSS)-exposed, GA-treated mice compared with control mice. This effect was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the expression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and pro-inflammatory cytokines. In addition, GA reduced the activation and nuclear accumulation of p-STAT3(Y705), preventing the degradation of the inhibitory protein IκB and inhibiting of the nuclear translocation of p65-NF-κB in colonic mucosa. These findings suggest that GA exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of p65-NF-κB and IL-6/p-STAT3(Y705) activation.

Matched MeSH terms: Nitric Oxide Synthase Type II
Fulltext Supplementation of 100% Flesh Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] Juice Improves Swimming Performance in Rats

Ridwan R, Razak HRA, Adenan MI, Saad WMM

Prev Nutr Food Sci, 2019 Mar;24(1):41-48.
PMID: 31008095 DOI: 10.3746/pnf.2019.24.1.41

Nutritional intervention of fruit juice supplementation is able to maximize exercise performance. Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] contains high L-citrulline content and consumption of watermelon juice may promote ergogenic effects. The aim of the present study was to investigate the role of 100% flesh watermelon juice and 100% rind watermelon juice supplementation for 14 days on swimming performance in rats. Twenty four male Sprague-Dawley rats were randomly divided into four groups: Cx group of rats supplemented with filtered tap water (negative control), L-cit group of rats supplemented with L-citrulline (positive control), FR group of rats supplemented with 100% flesh watermelon juice, and RR group of rats supplemented with 100% rind watermelon juice. Each group was supplemented for 14 days ad libitum prior to swimming exercise protocol. The rats were performed swimming exercise for 3 days and swimming time until exhaustion was measured. Plasma samples were collected to measure lactate concentration, ammonia concentration, and nitric oxide production. Rats supplemented with 100% flesh watermelon juice demonstrated significantly prolonged of swimming time until exhaustion, reduction of lactate and ammonia concentrations, and increased of nitric oxide production compared to Cx and L-cit groups (P<0.05). These findings postulate that supplementation with 100% flesh watermelon juice improves endurance in swimming performance.

Matched MeSH terms: Nitric Oxide
Vasorelaxant Action of the Chloroform Fraction of Orthosiphon stamineus via NO/cGMP Pathway, Potassium and Calcium Channels

Yam MF, Tan CS, Ahmad M, Ruan S

Am J Chin Med, 2016;44(7):1413-1439.
PMID: 27785939

Orthosiphon stamineus Benth. (Lamiaceae) is an important plant in traditional folk medicine that is used to treat hypertension and kidney stones. In humans, this plant has been tested as an addition regiment for antihypertensive treatment. Among the treatments for hypertension, O. stamineus had been to have diuretic and vasorelaxant effects in animal models. There is still very little information regarding the vasorelaxant effect of O. stamineus. Therefore, the present study was designed to investigate the vasorelaxant activity and mechanism of action of the fractions of O. stamineus. The vasorelaxant activity and the underlying mechanisms of the chloroform fraction of the 50% methanolic extract of O. stamineus (CF) was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. CF caused relaxation of the aortic ring pre-contracted with phenylephrine in the presence and absence of endothelium, and pre-contracted with potassium chloride in endothelium-intact aortic ring. In the presence of endothelium, both indomethacin (a nonselective cyclooxygenase inhibitor) and [Formula: see text]-[1,2,4]Oxadiazolo[4,3-[Formula: see text]]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor) had a small effect on the vasorelaxation response. On the other hand, in the presence of Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), tetraethylammonium ([Formula: see text], nonselective calcium activator [Formula: see text] channel blocker), 4-aminopyridine (4-AP, voltage-dependent [Formula: see text] channel blocker), barium chloride ([Formula: see text], inwardly rectifying [Formula: see text] channel blocker), glibenclamide (nonspecific ATP-sensitive [Formula: see text] channel blocker), atropine (muscarinic receptor blocker) and propranolol (β-adrenergic receptor blocker), the vasorelaxant effect significantly reduced the relaxation stimulated by CF. CF was also found to be active in reducing [Formula: see text] release from the sarcoplasmic reticulum and blocking calcium channels.

Matched MeSH terms: Nitric Oxide/metabolism*
Fulltext Preparation, antioxidant potential and angiotensin converting enzyme (ACE) inhibitory activity of gum arabic-stabilised magnesium orotate nanoparticles

Abdelkader Hassani, Siti Aslina Hussain?, Abdullah, N., Suryani Kamarudin, Rozita Rosli

International Food Research Journal, 2020;27(1):150-159.
MyJurnal

The present work investigated the antioxidant properties and antihypertensive activity of
magnesium orotate (MgOr) using various established in vitro assays, such as β-carotene
bleaching activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide scavenging activity as well as angiotensin converting enzyme (ACE) inhibitory activity. Magnesium orotate
nanoparticles (MgOrGANPs) were prepared using the gum arabic (GA) as stabiliser coatings
for nanoparticles through freeze-drying method. The in vitro cytoxicity of MgOrGANPs
against human breast cancer MCF7, liver cancer HepG2, and colon cancer HT29 was investigated. The nitric oxide (NO) and DPPH scavenging assays of MgOrGANPs showed a
dose-dependent trend, while 500 and 200 µL/mL were significantly more effective than the
other concentrations with an IC50 of 89.56 µg/mL and 63.22% DPPH scavenging capacity
respectively. The exposure of human cancer cells to MgOrGANPs at 1.56 – 1,000 µg/mL
using 3-)4,5-dimethylthiazol-2-yl(2,5-diphenyl tetrazolium bromide (MTT) inhibited the
growth of cell lines examined in a dose-dependent manner. Hence, MgOrGANPs may have
great potential to be applied for cancer treatments.

Matched MeSH terms: Nitric Oxide

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