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  1. 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: Guanosine Monophosphate
  2. Efficacy of purified nucleotide supplements on the growth performance and immunity of hybrid striped bass Morone chrysops x Morone saxatilis
    de Cruz CR, Yamamoto FY, Ju M, Chen K, Velasquez A, Gatlin DM
    Fish Shellfish Immunol, 2020 Mar;98:868-874.
    PMID: 31751660 DOI: 10.1016/j.fsi.2019.11.046
    Fishmeal is being increasingly replaced in aquatic animal diets with alternative plant protein feedstuffs such as soybean meal which have lower concentrations of nucleotides; therefore, supplemental sources of exogenous nucleotides in diets could become increasingly important. A 9-week feeding trial was conducted with triplicate groups of juvenile hybrid striped bass (average initial body weight ± standard deviation, 5.6 ± 0.1 g) to determine the effects of supplementing single purified nucleotides on the growth performance and immune parameters. The basal diet, which utilized menhaden fishmeal (25%) and soybean meal (75%) as protein sources, contained 44% protein, 10% lipid and an estimated digestible energy level of 3.5 kcal g-1. Single additions of 5'- adenosine monophosphate (AMP), 5'- uridine monophosphate (UMP), 5'- cytidine monophosphate (CMP), 5'- guanosine monophosphate (GMP), and 5'- inosine monophosphate (IMP) disodium salts (Chem-Impex International, Wood Dale, Illinois, USA) were evaluated with each nucleotide added to the basal diet at 0.5% of dry weight at the expense of cellulose. A positive control diet in this trial was a diet containing 5'- AMP from Sigma-Aldrich also supplemented at 0.5% by weight. Results showed significantly (P  0.05) was detected in whole-body proximate composition and protein retention of fish fed any of the dietary treatments. The respiratory burst of whole blood phagocytes also was significantly (P 
    Matched MeSH terms: Guanosine Monophosphate
  3. The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes
    Chew BL, Fisk ID, Fray R, Tucker GA, Bodi Z, Ferguson A, et al.
    Plant Cell Rep., 2017 Jan;36(1):81-87.
    PMID: 27662835 DOI: 10.1007/s00299-016-2058-z
    KEY MESSAGE: This study highlights the changes in umami-related nucleotide and glutamate levels when the AMP deaminase gene was elevated in transgenic tomato. Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway.
    Matched MeSH terms: Guanosine Monophosphate/metabolism
  4. Low-temperature and long-time heating regimes on non-volatile compound and taste traits of beef assessed by the electronic tongue system
    Ismail I, Hwang YH, Joo ST
    Food Chem, 2020 Aug 01;320:126656.
    PMID: 32224424 DOI: 10.1016/j.foodchem.2020.126656
    The influence of temperature-time combinations on non-volatile compound and taste traits of beef semitendinosus muscles tested by the electronic tongue was studied. Single-stage sous-vide at 60 and 70 °C (6 and 12 h), and two-stage sous-vide that sequentially cooked at 45 °C (3 h) and 60 °C (either 3 or 9 h) were compared with traditional cooking at 70 °C (30 min). Umami was better explained in the given model of partial least squares regression than astringency, sourness, saltiness, bitterness, and richness. Sous-vide at 70 °C for 12 h characterized the most umami, likely adenosine-5'-monophosphate (AMP) and guanosine-5'-monophosphate (GMP) as significant contributors. Two-stage sous-vide projected higher histidine, leucine, inosine, and hypoxanthine with the astringent and sour taste significant after 6 and 12 h cooking, respectively. Equivalent umami concentration (EUC) between umami amino acids and umami nucleotides showed a strong relationship to umami taste assessed by the electronic tongue.
    Matched MeSH terms: Guanosine Monophosphate/analysis
  5. Fulltext Methanolic Extract of Clinacanthus nutans Exerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways
    Abdul Rahim MH, Zakaria ZA, Mohd Sani MH, Omar MH, Yakob Y, Cheema MS, et al.
    Evid Based Complement Alternat Med, 2016;2016:1494981.
    PMID: 27190528 DOI: 10.1155/2016/1494981
    The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract of Clinacanthus nutans (Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p < 0.05) antinociceptive response in all nociceptive models with the recorded ED50 value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed by l-arginine (l-arg; a nitric oxide [NO] precursor), Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract's antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.
    Matched MeSH terms: Guanosine Monophosphate
  6. Fulltext Effects of germination conditions on 5'-phosphodiesterase activity of selected seeds
    Pui, L.P., Abdulkarim, S.M., Ghazali, H.M.
    International Food Research Journal, 2012;19(4):1641-1648.
    MyJurnal
    5'-Phosphodiesterase (5'-PDE) is an enzyme that hydrolyses RNA to form 5'-inosine monophosphate (5'-IMP) and 5'-guanosine monophosphate (5'-GMP), which function as flavour enhancers. Selection of the best producer of 5'-PDE was made by determining the activity of the enzyme in six seeds that have been germinated, namely mung bean (Vigna radiate), soybean (Glycine max), adzuki/red bean (Vigna angularis L.), chick pea (Cicer arietinum), black eye pea (Vigna unguiculata) and petai (Parkia speciosa). Seeds that were not germinated acted as the control. In order to ensure there is no contamination from potential 5'-PDE-producing microorganisms during germination, microbial growth was reduced by using different surface sterilizing treatments where the seeds were soaked in 100 mL solution containing different concentrations of sodium hypochlorite (with or without 0.05% sodium azide) for 5 minutes before rinsing it five times with sterilized distilled water (total 500 mL). The seeds were observed every day for 3 days and the best surface sterilizing treatment was selected based on absence of mold growth and the effects on hypocotyl length. Sodium hypochlorite at 0.3% (v/v) concentration was able to inhibit mold growth in adzuki bean, soybean and chickpea. On the other hand, only 0.1% (v/v) sodium hypochlorite was needed to inhibit mold growth in black eye pea and petai, while mung bean required 0.05% (v/v) sodium hypochlorite to inhibit mold growth. Under these conditions, the growth of hypocotyl (hypocotyls length) was only slightly affected compared to the control. 5'-PDE was extracted from seeds that have been germinated for 24 hours and their control (ungerminated seeds) by homogenization in a blender with 400 mL of 50 mM acetate buffer, pH 4.5. After that, the homogenates were stirred for 30 min and the centrifuged at 9000 rpm for 15 min at 10°C. 5'-PDE activity was determined using thymidine 5'-monophosphate p-nitrophenyl ester as substrate at pH 7.0 and 55°C. The formation of nucleotide monophosphates, the products of reaction, was determined at 405 nm. As a strong presence of phosphomonoesterase (PME) will reduce the yield of nucleotide monophosphates as the enzyme hydrolyzes these products into nucleosides and orthophosphate, PME activity was also determined using p-nitrophenyl phosphate as the substrate at 60°C and pH 5.0. Thus, the seed with the highest 5'-PDE activity and a low PME activity can be selected. Germinated adzuki bean was found to have the highest 5'-PDE activity (0.59 µmol p-nitrophenol/min/mg protein) among the germinated seeds. A time-course study indicated that the level of 5'-PDE in adzuki bean increased with time of germination until 15 hours (0.69 µmol p-nitrophenol/min/mg protein), after which the acitivity decreased until it reached the basal level (0.44 µmol p-nitrophenol/min/mg protein) at 72 hours. On the other hand, PME in the bean was the highest at 9 h germination (0.98 µmol p-nitrophenol/min/mg protein). In general, controls have very low basal level of 5'-PDE activity (0.18- 0.42 µmol p-nitrophenol/min/mg protein).
    Matched MeSH terms: Guanosine Monophosphate
  7. Influence of fresh and thermoxidized carotino oil on cyclic guanosine monophosphate (cGMP) in erythrocytes from sprague dawley rats
    Mohd Fakharul Zaman Raja Yahyai, Athifah Najwani Shahidan
    Scientific Research Journal, 2012;9(1):63-74.
    MyJurnal
    Cyclic guanosine monophosphate (cGMP) is a second messenger molecule involved in the intracellular signalling mechanism which is important in a wide range of cellular process including metabolism, gene expression, cell proliferation and cell death. This study was conducted to determine the effect of fresh (FCC)) and thermoxidized carotino oil (TCO) on erythrocyte cGMP levels from Sprague dawley rats. A total of 30 Sprague dawley rats were randomly segregated into three groups: the first of which was placed on a Fresh Carotino Oil (FCO) diet, the second on a Thermoxidized Carotino Oil (TCO) diet and the control group on commercial rat chow only for a period of 6 and 9 weeks. The two oil diets comprised of 20% (w.10 of each oil mixed with commercial rat,feed. The enzyme immunoassays, performed in week 6, revealed that the erythrocytes cGMP levels for the FCO and TCO groups were 66.198±3.193 pmol/mL and 61.990±6.318 ptnol/mL respectively, and were significantly (p
    Matched MeSH terms: Guanosine Monophosphate
  8. Fluorescence polarisation for high-throughput screening of adulterated food products via phosphodiesterase 5 inhibition assay
    Mohd Yusop AY, Xiao L, Fu S
    Drug Test Anal, 2020 Sep 22.
    PMID: 32959983 DOI: 10.1002/dta.2926
    The surge in the consumption of food products containing herbal aphrodisiacs has driven their widespread adulteration. A rapid screening strategy is, therefore, warranted to curb this problem. This study established an enzyme inhibition assay to screen phosphodiesterase 5 (PDE5) inhibitors as adulterants in selected food products. Fluorescein-labelled cyclic-3',5'-guanosine monophosphate was utilised as substrates for the PDE5A1 enzyme, aided by the presence of nanoparticle phosphate-binding beads on their fluorescence polarisation. The sample preparation was optimised to improve the enzyme inhibition efficiency and applied to calculate the threshold values of six blank food matrices. The assay was validated using sildenafil, producing an IC50 of 4.2 nM. The applicability of the assay procedure was demonstrated by screening 55 distinct food samples. The results were subsequently verified using confirmatory liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis. Altogether, 49 samples inhibited the PDE5 enzyme above the threshold values (75.7%-105.5%) and were registered as potentially adulterated samples. The remaining six samples were marked as nonadulterated with percentage inhibition below the threshold values (-3.3%-18.2%). The LC-HRMS analysis agreed with the assay results for all food products except for the instant coffee premix (ICP) samples. False-positive results were obtained for the ICP samples at 32% (8/25), due to possible PDE5 inhibition by caffeine. Contrarily, all other food samples were found to produce 0% (0/30) false-positive or false-negative results. The broad-based assay, established via a simple mix-incubate-read format, exhibited promising potential for high-throughput screening of PDE5 inhibitors in various food products, except those with naturally occurring phosphodiesterase inhibitors such as caffeine.
    Matched MeSH terms: Guanosine Monophosphate
  9. Fulltext Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models
    Pui Ping C, Akhtar MN, Israf DA, Perimal EK, Sulaiman MR
    Molecules, 2020 Nov 18;25(22).
    PMID: 33217904 DOI: 10.3390/molecules25225385
    The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.
    Matched MeSH terms: Guanosine Monophosphate
  10. Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe
    Lin DS, Wang TD, Buranakitjaroen P, Chen CH, Cheng HM, Chia YC, et al.
    J Clin Hypertens (Greenwich), 2020 Dec 11.
    PMID: 33305531 DOI: 10.1111/jch.14120
    Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.
    Matched MeSH terms: Guanosine Monophosphate
  11. Vasorelaxant effect of water fraction of Labisia Pumila and its mechanisms in spontaneously hypertensive rats aortic ring preparation
    Manshor NM, Razali N, Jusoh RR, Asmawi MZ, Mohamed N, Zainol S, et al.
    Int J Cardiol Hypertens, 2020 Mar;4:100024.
    PMID: 33447753 DOI: 10.1016/j.ijchy.2020.100024
    Introduction: Labisia pumila has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects.

    Objective: This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects.

    Methods: Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction.

    Results: WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca2+) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE.

    Conclusion: WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.

    Matched MeSH terms: Guanosine Monophosphate
  12. Metformin mitigates impaired testicular lactate transport/utilisation and improves sexual behaviour in streptozotocin-induced diabetic rats
    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: Guanosine Monophosphate
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