Displaying publications 21 - 40 of 127 in total

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  1. Zakaria ZA, Sulaiman MR, Jais AM, Somchit MN, Jayaraman KV, Balakhrisnan G, et al.
    Fundam Clin Pharmacol, 2006 Aug;20(4):365-72.
    PMID: 16867020
    The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.
    Matched MeSH terms: Nitric Oxide/metabolism*
  2. Yong YK, Zakaria ZA, Kadir AA, Somchit MN, Ee Cheng Lian G, Ahmad Z
    PMID: 23410184 DOI: 10.1186/1472-6882-13-32
    Bixa orellana L. has been traditionally used in Central and South America to treat a number of ailments, including internal inflammation, and in other tropical countries like Malaysia as treatment for gastric ulcers and stomach discomfort. The current study aimed to determine the major chemical constituents of the aqueous extract of B. orellana (AEBO) and to evaluate the antihistamine activity of AEBO during acute inflammation induced in rats.
    Matched MeSH terms: Nitric Oxide/metabolism
  3. Mohd Ali N, Mohd Yusof H, Long K, Yeap SK, Ho WY, Beh BK, et al.
    Biomed Res Int, 2013;2013:693613.
    PMID: 23484140 DOI: 10.1155/2013/693613
    Mung bean is a hepatoprotective agent in dietary supplements. Fermentation and germination processes are well recognized to enhance the nutritional values especially the concentration of active compounds such as amino acids and GABA of various foods. In this study, antioxidant and hepatoprotective effects of freeze-dried mung bean and amino-acid- and GABA-enriched germinated and fermented mung bean aqueous extracts were compared. Liver superoxide dismutase (SOD), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), nitric oxide (NO) levels, and serum biochemical profile such as aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TG), and cholesterol and histopathological changes were examined for the antioxidant and hepatoprotective effects of these treatments. Germinated and fermented mung bean have recorded an increase of 27.9 and 7.3 times of GABA and 8.7 and 13.2 times of amino acid improvement, respectively, as compared to normal mung bean. Besides, improvement of antioxidant levels, serum markers, and NO level associated with better histopathological evaluation indicated that these extracts could promote effective recovery from hepatocyte damage. These results suggested that freeze-dried, germinated, and fermented mung bean aqueous extracts enriched with amino acids and GABA possessed better hepatoprotective effect as compared to normal mung bean.
    Matched MeSH terms: Nitric Oxide/metabolism
  4. Bello I, Usman NS, Mahmud R, Asmawi MZ
    J Ethnopharmacol, 2015 Dec 4;175:422-31.
    PMID: 26429073 DOI: 10.1016/j.jep.2015.09.031
    Alstonia scholaris has a long history of use in the Ayurveda traditional treatment of various ailments including hypertension. We have reported the blood pressure lowering activity of the extract of A. scholaris. The following research aim to delineate the pharmacological mechanism involve in the antihypertensive action.
    Matched MeSH terms: Nitric Oxide/metabolism
  5. Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR
    PLoS One, 2015;10(10):e0139593.
    PMID: 26427053 DOI: 10.1371/journal.pone.0139593
    Amauroderma rugosum, commonly known as "Jiǎzī" in China, is a wild mushroom traditionally used by the Chinese to reduce inflammation, to treat diuretic and upset stomach, and to prevent cancer. It is also used by the indigenous communities in Malaysia to prevent epileptic episodes and incessant crying by babies. The aim of this study was to compare the wild and domesticated basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were collected from the Belum Forest, Perak, Malaysia and the domesticated basidiocarps of A. rugosum were cultivated in the mushroom house located in the University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated basidiocarps were subjected to ethanolic extraction and the extracts were tested for antioxidant and anti-inflammatory activities. In this study, the crude ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum had comparable total phenolic content and DPPH scavenging activity. However, WB (EC50 = 222.90 μg/mL) displayed a better ABTS cation radical scavenging activity than DB (EC50 = 469.60 μg/mL). Both WB and DB were able to scavenge nitric oxide (NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and this effect was mediated through the down-regulation of inducible nitric oxide synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the inflammatory gene TNF-α and the up-regulation of the anti-inflammatory gene IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF-κB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum possessed antioxidant and in vitro anti-inflammatory properties. WB and DB inhibited downstream inflammatory mediators (TNF-α and NO) and induced anti-inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream nuclear translocation of NF-κB p65. WB and DB exhibited antioxidant activity and attenuation of proinflammatory mediators and therefore, A. rugosum may serve as a potential therapeutic agent in the management of inflammation.
    Matched MeSH terms: Nitric Oxide/metabolism*
  6. 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
  7. Mokhtar SS, Vanhoutte PM, Leung SW, Suppian R, Yusof MI, Rasool AH
    Eur J Pharmacol, 2016 Feb 15;773:78-84.
    PMID: 26825543 DOI: 10.1016/j.ejphar.2016.01.013
    Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 ± 2.48% versus 85.05 ± 3.15%). Incubation with the combination of non-selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 ± 5.84% versus 68.39 ± 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 ± 6.74% versus 34.16 ± 4.59%) (prostacyclin; 15.85 ± 3.27% versus 17.23 ± 3.75%)]. Endothelium-independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction.
    Matched MeSH terms: Nitric Oxide/metabolism*
  8. Harun A, Vidyadaran S, Lim SM, Cole AL, Ramasamy K
    PMID: 26047814 DOI: 10.1186/s12906-015-0685-5
    Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines like tumour necrosis factor-alpha (TNF-α) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. This study investigated the protective role of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) against LPS-induced inflammatory events in vitro. These endophytic extracts were previously found to exhibit potent neuroprotective effect against LPS-challenged microglial cells.
    Matched MeSH terms: Nitric Oxide/metabolism
  9. Lau YS, Ling WC, Murugan D, Kwan CY, Mustafa MR
    Nutrients, 2015 Jul;7(7):5239-53.
    PMID: 26133970 DOI: 10.3390/nu7075220
    Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE), also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma "antihypertensive tea" is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs). Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase), wortmannin (30 nM) and LY294002 (20 µM; PI3 (phosphatidylinositol3)-Kinase inhibitor), N(G)-nitro-L-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS)) and ODQ (1 µM; soluble guanylyl cyclase inhibitor). Total nitrite and nitrate (NOx) level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity.
    Matched MeSH terms: Nitric Oxide/metabolism
  10. Kanwar JR, Samarasinghe RM, Kumar K, Arya R, Sharma S, Zhou SF, et al.
    Drug Des Devel Ther, 2015;9:2927-40.
    PMID: 26089642 DOI: 10.2147/DDDT.S77369
    INTRODUCTION: Inflammatory mediators are key players in the pathogenesis of osteoarthritis (OA) and bone destruction. Conventional drugs suppress symptomatic activity and have no therapeutic influence on disease. Cissus quadrangularis and Withania somnifera are widely used for the treatment of bone fractures and wounds; however, the cellular and molecular mechanisms regulated by these herbals are still unclear.

    METHODS: We established an in vitro OA culture model by exposing human chondrocytes to proinflammatory cytokine and interleukin (IL)-1β for 36 hours prior to treatment with the herbals: C. quadrangularis, W. somnifera, and the combination of the two herbals. Cell viability, toxicity, and gene expression of OA modifying agents were examined. In addition, expression of survivin, which is crucial for cell growth, was analyzed. In vivo work on osteotomized rats studied the bone and cartilage regenerative effects of C. quadrangularis, W. somnifera, and the combination therapy.

    RESULTS: Exposure of chondrocytes to IL-1β induced significant toxicity and cell death. However, herbal treatment alleviated IL-1β induced cell toxicity and upregulated cell growth and proliferation. C. quadrangularis inhibited gene expression of cytokines and matrix metalloproteinases, known to aggravate cartilage and bone destruction, and augmented expression of survivin by inhibiting p38 MAPK. Interestingly, osteotomized rats treated with C. quadrangularis drastically enhanced alkaline phosphatase and cartilage tissue formation as compared to untreated, W. somnifera only, or the combination of both herbals.

    CONCLUSION: Our findings demonstrate for the first time the signaling mechanisms regulated by C. quadrangularis and W. somnifera in OA and osteogenesis. We suggest that the chondroprotective effects and regenerative ability of these herbals are via the upregulation of survivin that exerts inhibitory effects on the p38 MAPK signaling pathway. These findings thus validate C. quadrangularis as a potential therapeutic for rheumatic disorders.

    Matched MeSH terms: Nitric Oxide/metabolism
  11. Abu N, Mohamed NE, Yeap SK, Lim KL, Akhtar MN, Zulfadli AJ, et al.
    Anticancer Agents Med Chem, 2015;15(7):905-15.
    PMID: 26179368
    Flavokawain A is a chalcone that can be found in the kava-kava plant (Piper methsyticum) extract. The kava-kava plant has been reported to possess anti-cancer, anti-inflammatory and antinociceptive activities. The state of the immune system, and the inflammatory process play vital roles in the progression of cancer. The immunomodulatary effects and the anti-inflammatory effects of flavokawain A in a breast cancer murine model have not been studied yet. Thus, this study aimed to elucidate the basic mechanism as to how flavokawain A regulates and enhance the immune system as well as impeding the inflammatory process in breast cancer-challenged mice. Based on our study, it is interesting to note that flavokawain A increased the T cell population; both Th1 cells and CTLs, aside from the natural killer cells. The levels of IFN-γ and IL-2 were also elevated in the serum of flavokawain A-treated mice. Apart from that, flavokawain A also decreased the weight and volume of the tumor, and managed to induce apoptosis in them. In terms of inflammation, flavokawain A-treated mice had reduced level of major pro-inflammatory mediators; NO, iNOS, NF-KB, ICAM and COX-2. Overall, flavokawain A has the potential to not only enhance antitumor immunity, but also prevents the inflammatory process in a cancer-prone microenvironment.
    Matched MeSH terms: Nitric Oxide/metabolism
  12. 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*
  13. 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/metabolism*
  14. Azhar NA, Ghozali SZ, Abu Bakar SA, Lim V, Ahmad NH
    Toxicol In Vitro, 2020 Sep;67:104910.
    PMID: 32526345 DOI: 10.1016/j.tiv.2020.104910
    Application of silver nanoparticles serves as a new approach in cancer treatment due to its unique features. Biosynthesis of silver nanoparticles using plant is advantageous since they are easily accessible, nontoxic and produce quicker reaction compared to other methods. To evaluate the cytotoxicity, mechanism of cell death and DNA damage of biosynthesized Catharanthus roseus-silver nanoparticles on human liver cancer (HepG2) cells. The antiproliferative activity of Catharanthus roseus‑silver nanoparticles was measured using MTT assay. The cytotoxic effects were further evaluated by measuring nitric oxide and reactive oxygen species (ROS). The mechanism of cell death was determined by annexin-FITC/propidium iodide, mitochondrial membrane potential (MMP) and cell cycle assays. The assessment of DNA damage was evaluated using Comet assay method. The uptake of the nanoparticles were evaluated by Transmission Electron Microscopy (TEM). Catharanthus roseus‑silver nanoparticles has inhibited the proliferation of HepG2 cells in a time-dependent manner with a median IC50 value of 3.871 ± 0.18 μg/mL. The concentration of nitrite and ROS were significantly higher than control. The cell death was due to apoptosis associated with MMP loss, cell cycle arrest, and extensive DNA damage. TEM analysis indicated the presence of free nanoparticles and endosomes containing the nanoparticles. The findings show that Catharanthus roseus‑silver nanoparticles have produced cytotoxic effects on HepG2 cells and thus may have a potential to be used as an anticancer treatment, particularly for hepatocellular carcinoma.
    Matched MeSH terms: Nitric Oxide/metabolism
  15. Nna VU, Abu Bakar AB, Ahmad A, Mohamed M
    Arch Physiol Biochem, 2021 Feb;127(1):51-60.
    PMID: 31072137 DOI: 10.1080/13813455.2019.1610778
    CONTEXT: Lactate is the preferred energy substrate for developing testicular germ cells. Diabetes is associated with impaired testicular lactate transport/utilisation, and poor sexual behaviour.

    OBJECTIVE: To examine the effects of metformin on parameters involved in testicular lactate production, transport/utilisation, and sexual behaviour in diabetic state.

    METHODS: Male Sprague-Dawley rats were assigned into normal control (NC), diabetic control (DC), and metformin-treated diabetic group (n = 6/group). Metformin (300 mg/kg b.w./day) was administrated orally for 4 weeks.

    RESULTS: Intra-testicular glucose and lactate levels, and lactate dehydrogenase (LDH) activity increased, while the mRNA transcript levels of genes responsible for testicular glucose and lactate transport/utilisation (glucose transporter 3, monocarboxylate transporter 4 (MCT4), MCT2, and LDH type C) decreased in DC group. Furthermore, penile nitric oxide increased, while cyclic guanosine monophosphate decreased, with impaired sexual behaviour in DC group. Treatment with metformin improved these parameters.

    CONCLUSIONS: Metformin increases testicular lactate transport/utilisation and improves sexual behaviour in diabetic state.

    Matched MeSH terms: Nitric Oxide/metabolism
  16. Siti HN, Jalil J, Asmadi AY, Kamisah Y
    Int J Mol Sci, 2021 May 11;22(10).
    PMID: 34064664 DOI: 10.3390/ijms22105063
    Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 μM) or rutin (50 μM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.
    Matched MeSH terms: Nitric Oxide/metabolism
  17. Ahmad MH, Zezi AU, Anafi SB, Alhassan Z, Mohammed M, Danraka RN
    J Ethnopharmacol, 2021 Apr 06;269:113750.
    PMID: 33359856 DOI: 10.1016/j.jep.2020.113750
    ETHNOPHARMACOLOGICAL RELEVANCE: The plant Combretum hypopilinum Diels (Combretaceae) is used in traditional medicine for the treatment of diarrhoea and other diseases in Africa. Previously, the antidiarrhoeal activity of its methanol leaf extract was reported. However, the mechanism(s) responsible for this activity is yet to be evaluated.

    AIM OF THE STUDY: This study aimed to elucidate the possible mechanism(s) of antidiarrhoeal activity of methanol leaf extract of Combretum hypopilinum (MECH) in mice.

    MATERIALS AND METHODS: Phytochemical screening and acute toxicity study were conducted according to standard methods. Adult mice were orally (p.o) administered distilled water (10 ml/kg), MECH (1000 mg/kg) and loperamide (5 mg/kg). The probable mechanisms of antidiarrhoeal activity of MECH were investigated following pretreatment with naloxone (2 mg/kg, subcutaneously), prazosin (1 mg/kg, s.c), yohimbine (2 mg/kg, intraperitoneally), propranolol (1 mg/kg, i.p), pilocarpine (1 mg/kg, s.c) and isosorbide dinitrate (150 mg/kg, p.o) 30 min before administration of MECH (1000 mg/kg). The mice were then subjected to castor oil-induced intestinal motility test.

    RESULTS: The oral median lethal dose (LD50) of MECH was found to be higher than 5000 mg/kg. There were significant (p 

    Matched MeSH terms: Nitric Oxide/metabolism
  18. Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, et al.
    Emerg Microbes Infect, 2018 Jun 06;7(1):106.
    PMID: 29872039 DOI: 10.1038/s41426-018-0105-2
    Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.
    Matched MeSH terms: Nitric Oxide/metabolism
  19. Swamy M, Zakaria AZ, Govindasamy C, Sirajudeen KN, Nadiger HA
    Neurosci Res, 2005 Oct;53(2):116-22.
    PMID: 16009439
    Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects.
    Matched MeSH terms: Nitric Oxide/metabolism*
  20. Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.
    J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
    PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015
    Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.
    Matched MeSH terms: Nitric Oxide/metabolism
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