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Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain

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*; Nitric Oxide Synthase/drug effects; Nitric Oxide Synthase/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
Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells

Liew CY, Lam KW, Kim MK, Harith HH, Tham CL, Cheah YK, et al.

Int Immunopharmacol, 2011 Jan;11(1):85-95.
PMID: 21035434 DOI: 10.1016/j.intimp.2010.10.011

We previously showed that 3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l)propenone (HMP), suppressed the synthesis of various proinflammatory mediators. In this study, HMP showed a dose-dependent inhibition of NO synthesis in the RAW 264.7 murine macrophage line. The inhibition of NO synthesis was related to inhibition of p38 phosphorylation and kinase activity that led to significant inhibition of phosphorylation of ATF-2. This effect in turn caused inhibition of AP-1-DNA binding which partially explains the inhibitory effect upon the synthesis of iNOS. HMP had no effect upon phosphorylation of JNK, ERK1/2 and STAT-1. Kinase activity of JNK and ERK1/2 was also not affected by HMP as determined by levels of phosphorylated c-jun and phosphorylated elk-1. Furthermore HMP failed to block phosphorylation of IκBα, and subsequent nuclear translocation and DNA-binding activity of p65 NF-κB in IFN-γ/LPS-induced RAW 264.7 cells. Molecular docking experiments confirmed that HMP fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We conclude that the synthetic HMP is a chalcone analogue that selectively inhibits the p38/ATF-2 and AP-1 signaling pathways in the NO synthesis by the macrophage RAW 264.7.

Matched MeSH terms: Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/antagonists & inhibitors*; Nitric Oxide Synthase Type II/biosynthesis
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
Fulltext Antioxidant, α-Glucosidase, and Nitric Oxide Inhibitory Activities of Six Algerian Traditional Medicinal Plant Extracts and 1H-NMR-Based Metabolomics Study of the Active Extract

Hellal K, Maulidiani M, Ismail IS, Tan CP, Abas F

Molecules, 2020 Mar 10;25(5).
PMID: 32164186 DOI: 10.3390/molecules25051247

Claims of effective therapy against diabetes using plants including Peganum harmala L., Zygophyllum album, Anacyclus valentinus L., Ammodaucus leucotrichus, Lupinus albus, and Marrubium vulgare in Algerian empirical medicine prompted our interest in evaluating their antidiabetic activity by screening their free radical scavenging (DPPH), α-glucosidase, and nitric oxide (NO) inhibitory activities as well as the total phenolic content (TPC). Extracts of the selected plants were prepared using different ratios of ethanol (0, 50, 80, and 100%). In this study, 100%, and 80% ethanol extracts of L. albus were found to be the most potent, in inhibiting α-glucosidase activity with IC50 values of 6.45 and 8.66 μg/mL, respectively. The 100% ethanol extract of A. leucotrichus exhibited the highest free radical scavenging activity with an IC50 value of 26.26 μg/mL. Moreover, the highest TPC of 612.84 μg GAE/mg extract was observed in M. vulgare, extracted with 80% ethanol. Metabolite profiling of the active extract was conducted using 1H-NMR metabolomics. Partial least square analysis (PLS) was used to assess the relationship between the α-glucosidase inhibitory activity of L. albus and the metabolites identified in the extract. Based on the PLS model, isoflavonoids (lupinoisoflavone G, lupisoflavone, lupinoisolone C), amino acids (asparagine and thiamine), and several fatty acids (stearic acid and oleic acid) were identified as metabolites that contributed to the inhibition of α-glucosidase activity. The results of this study have clearly strengthened the traditional claim of the antihyperglycemic effects of L. albus.

Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide/chemistry*
Nitric oxide production by murine spleen cells stimulated with Porphyromonas gingivalis-derived lipopolysaccharide

Sosroseno W

Asian Pac J Allergy Immunol, 2000 Dec;18(4):209-14.
PMID: 11316041

The aim of the present study was to determine whether Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) may stimulate nitric oxide (NO) production by murine spleen cells. Spleen cells derived from Balb/c mice were cultured in the presence of Pg-LPS or LPS from Salmonella Typhosa. The cell were also cultured in the presence of Pg-LPS with or without L-arginine, L-arginine plus NG-monomethyl-L-arginine (NMMA), or IFN-gamma. Furthermore, the plastic non-adherent spleen cells were stimulated with Pg-LPS and L-arginine. The results showed that Pg-LPS failed to stimulate splenic NO production by themselves. Exogenous L-arginine or IFN-gamma up-regulated the NO production of Pg-LPS-stimulated spleen cells, but the stimulatory effects of L-arginine were completely blocked by NMMA. It was also demonstrated that in the presence of Pg-LPS and L-arginine, splenic macrophages were the cellular source of NO. These results suggest, therefore, that P. gingivalis-LPS may induce murine splenic macrophages to produce NO in a L-arginine and an IFN-gamma-dependent mechanism.

Matched MeSH terms: Nitric Oxide/biosynthesis*; Nitric Oxide/metabolism
Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury

Tan PS, Genc F, Delgado E, Kellum JA, Pinsky MR

Intensive Care Med, 2002 Aug;28(8):1064-72.
PMID: 12185426

We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx).

Matched MeSH terms: Nitric Oxide/administration & dosage*; Nitric Oxide/adverse effects
Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities

Lee KH, Ab Aziz FH, Syahida A, Abas F, Shaari K, Israf DA, et al.

Eur J Med Chem, 2009 Aug;44(8):3195-200.
PMID: 19359068 DOI: 10.1016/j.ejmech.2009.03.020

A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-gamma/LPS-activated RAW 264.7 cells as compared to L-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents.

Matched MeSH terms: Nitric Oxide/biosynthesis; Nitric Oxide/metabolism
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
Bixa orellana leaves extract inhibits bradykinin-induced inflammation through suppression of nitric oxide production

Yoke Keong Y, Arifah AK, Sukardi S, Roslida AH, Somchit MN, Zuraini A

Med Princ Pract, 2011;20(2):142-6.
PMID: 21252569 DOI: 10.1159/000319907

The present study was conducted to assess the anti-inflammatory effect of a crude aqueous extract of Bixa orellana leaves (AEBO) and to examine the possible involvement of nitric oxide (NO) in its anti-inflammatory mechanism.

Matched MeSH terms: Nitric Oxide/antagonists & inhibitors*; Nitric Oxide/biosynthesis
Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells

Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, et al.

Inflamm Res, 2010 Sep;59(9):711-21.
PMID: 20221843 DOI: 10.1007/s00011-010-0182-8

OBJECTIVES: We evaluated several flavonoid combinations for synergy in the inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular model of inflammation.
METHODS: The inhibitory effect of chrysin, kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumour necrosis factor-alpha (TNF-alpha) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC(50) values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC(50) ratios and reassessed for inhibition of NO, PGE(2) and TNF-alpha. Dose-response curves were generated and interactions were analysed using isobolographic analysis.
RESULTS: The experiments showed that only chrysin, kaempferol, morin, and silibinin were potent enough to produce dose-response effects upon at least two out of the three mediators assayed. Combinations of these four flavonoids showed that several combinations afforded highly significant synergistic effects.
CONCLUSIONS: Some flavonoids are synergistic in their anti-inflammatory effects when combined. In particular chrysin and kaempferol significantly synergised in their inhibitory effect upon NO, PGE(2) and TNF-alpha secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.

Matched MeSH terms: Nitric Oxide/antagonists & inhibitors*; Nitric Oxide/metabolism
Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-kappaB nuclear translocation and Ikappa-B phosphorylation in RAW 264.7 macrophage cells

Israf DA, Khaizurin TA, Syahida A, Lajis NH, Khozirah S

Mol Immunol, 2007 Feb;44(5):673-9.
PMID: 16777230

Cardamonin, a chalcone isolated from the fruits of a local plant Alpinia rafflesiana, has demonstrated anti-inflammatory activity in cellular models of inflammation. In this report, we evaluated the ability of cardamonin to suppress both NO and PGE2 synthesis, iNOS and COX-2 expression and enzymatic activity, and key molecules in the NF-kappaB pathway in order to determine its molecular target. Cardamonin suppressed the production of NO and PGE2 in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells. This inhibition was demonstrated to be caused by a dose-dependent down-regulation of both inducible enzymes, iNOS and COX-2, without direct effect upon iNOS or COX-2 enzyme activity. Subsequently we determined that the inhibition of inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation and degradation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation. We conclude that cardamonin is a potential anti-inflammatory drug lead that targets the NF-kappaB pathway.

Matched MeSH terms: Nitric Oxide Synthase Type II/antagonists & inhibitors*; Nitric Oxide Synthase Type II/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
Effect of inhibition of inducible nitric oxide synthase (iNOS) on the murine splenic immune response induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans lipopolysaccharide

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

Eur J Oral Sci, 2008 Feb;116(1):31-6.
PMID: 18186729 DOI: 10.1111/j.1600-0722.2007.00501.x

Animal studies suggest that inducible nitric oxide synthase (iNOS) may be associated with destructive periodontal disease. l-N(6)-(1-Iminoethyl)-lysine (L-NIL) has been shown to inhibit iNOS in a selective manner, and hence the aim of the present study was to test the hypothesis that treatment with l-NIL may induce a T-cell helper 1 (Th1)-like immune response by Aggregatibacter (Actinobacillus) actinomycetemcomitans lipopolysaccharide (LPS)-stimulated murine spleen cells in vitro. BALB/c mice were either sham-immunized or immunized with A. actinomycetemcomitans LPS. Spleen cells were stimulated with A. actinomycetemcomitans LPS in the presence or absence of L-NIL. Nitric oxide (NO), iNOS activity, specific IgG subclass antibodies, interferon-gamma (IFN-gamma), and interleukin-4 (IL-4) levels and cell proliferation were determined. The results showed that treatment with L-NIL suppressed both NO production and iNOS activity but enhanced specific IgG2a, IFN-gamma levels, and increased cell proliferation following stimulation with A. actinomycetemcomitans LPS-stimulated cells. The results of the present study suggest that inhibition of iNOS activity by L-NIL may skew the A. actinomycetemcomitans LPS-stimulated murine splenic immune response towards the Th1-like immune profile in vitro.

Matched MeSH terms: Nitric Oxide Synthase Type II/analysis; Nitric Oxide Synthase Type II/antagonists & inhibitors*
Agarwood oil nanoemulsion counteracts LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages

Malik R, Paudel KR, Manandhar B, De Rubis G, Shen J, Mujwar S, et al.

Pathol Res Pract, 2023 Nov;251:154895.
PMID: 37879146 DOI: 10.1016/j.prp.2023.154895

PURPOSE: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE'RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro.
METHODS: The antioxidant and anti-inflammatory activity of DE'RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE'RAAQSIN were investigated via qPCR.
RESULTS: LPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-α, IL-1β, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE'RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-α, IL-1β, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components.
CONCLUSIONS: We propose DE'RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE'RAAQSIN.

Matched MeSH terms: Nitric Oxide/metabolism; Nitric Oxide/therapeutic use
Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling pathway

Ooi TC, Chan KM, Sharif R

Immunopharmacol Immunotoxicol, 2017 Oct;39(5):259-267.
PMID: 28697633 DOI: 10.1080/08923973.2017.1344987

CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer.
OBJECTIVE: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages.
MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay.
RESULTS: Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine.
CONCLUSION: Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

Matched MeSH terms: Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/biosynthesis
Fulltext Quantitative real-time PCR analysis of Anopheles dirus TEP1 and NOS during Plasmodium berghei infection, using three reference genes

Liew JWK, Fong MY, Lau YL

PeerJ, 2017;5:e3577.
PMID: 28761783 DOI: 10.7717/peerj.3577

Quantitative reverse transcription PCR (qRT-PCR) has been an integral part of characterizing the immunity of Anopheles mosquitoes towards Plasmodium invasion. Two anti-Plasmodium factors of Anopheles, thioester-containing protein 1 (TEP1) and nitric oxide synthase (NOS), play a role in the refractoriness of Anopheles towards Plasmodium infection and are generally expressed during infection. However, these are less studied in Anopheles dirus, a dominant malaria vector in Southeast Asia. Furthermore, most studies used a single reference gene for normalization during gene expression analysis without proper validation. This may lead to erroneous quantification of expression levels. Therefore, the present study characterized and investigated the expression profiles of TEP1 and NOS of Anopheles dirus during P. berghei infection. Prior to that, the elongation factor 1-alpha (EF1), actin 1 (Act) and ribosomal protein S7 (S7) genes were validated for their suitability as a set of reference genes. TEP1 and NOS expressions in An. dirus were found to be significantly induced after P. berghei infection.

Matched MeSH terms: Nitric Oxide Synthase
Fulltext Metabolite characterization of different palm date varieties and the correlation with their NO inhibitory activity, texture and sweetness

Abdul-Hamid NA, Mediani A, Maulidiani M, Shadid K, Ismail IS, Abas F, et al.

J Food Sci Technol, 2018 Apr;55(4):1541-1551.
PMID: 29606769 DOI: 10.1007/s13197-018-3073-6

The aim of this study was to examine the variation in metabolite constituents of five commercial varieties of date fruits; Ajwa, Safawi and Ambar which originated from Madinah, the Iranian Bam and Tunisian Deglet Noor. The differences of metabolome were investigated using proton nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate data analysis (MVDA). Principal Component Analysis (PCA) revealed clear separation between the date varieties. The Tunisian Deglet Noor demonstrated distinct cluster from the rest of the palm date samples based on the metabolite composition as shown by the pattern observed in Hierarchical Clustering Analysis (HCA) and PCA. Deglet Noor exhibited a significant higher level of sucrose (δ 5.40) and fructose (δ 4.16) in comparison with the other four varieties which can be associated with the distinctive sweet taste of this variety. Dates originated from Madinah and Tunisia exhibited a contrast manner in the amount of xylose and moisture content. These two aspects may contribute towards the soft texture of Tunisian dates. All Madinah dates were found to contain phenolic compounds which were well established as great antioxidant and anti-inflammatory agent. Ajwa dates exerted greater effect in inhibiting the generation of nitric oxide (NO) from the stimulated RAW264.7 cells at 95.37% inhibition. Succinic acid was suggested to have the most significant correlation with the trend of NO inhibitory shown by the selected date palm varieties.

Matched MeSH terms: Nitric Oxide
Fulltext Role of nitric oxide-scavenging activity of Karanjin and Pongapin in the treatment of Psoriasis

Ghosh A, Tiwari GJ

3 Biotech, 2018 Aug;8(8):338.
PMID: 30073123 DOI: 10.1007/s13205-018-1337-5

In the present study, Karanjin and Pongapin, two important furanoflavone, constituents of Pongamia pinnata were studied in the management of Psoriasis. Presently, we have experimentally studied the free radical quenching property of Karanjin and Pongapin. A modified method was used to estimate the scavenging effect of the Karanjin (the highest activity of 95.60%) and Pongapin (68.05%) compared to the ascorbic acid as standard (11.60%) against nitric oxide. Furthermore, Molecular docking studies were performed using CLC drug discovery workbench software version 3.0 of the studied flavones (Karanjin and Pongapin) with the receptors responsible for psoriasis (viz. IL-17A, IL-17F, IL-23, RORγt, and TLR-7). Docking scores of Karanjin and Pongapin with different studied receptors were found to be comparable to that of Methotrexate, a known drug for treating Psoriasis. Docking results suggest that Karanjin and Pongapin might also help in controlling the disease. Overall, our results indicate that flavones (Karanjin and Pongapin) could be a natural and better alternative in curing psoriasis without any side effects.

Matched MeSH terms: Nitric Oxide
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

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