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  1. 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*
  2. Gopinath VK, Musa M, Samsudin AR, Lalitha P, Sosroseno W
    Arch Oral Biol, 2006 Apr;51(4):339-44.
    PMID: 16214104
    The aim of this study was to determine the role of nitric oxide (NO) in hydroxyapatite (HA)-induced phagocytosis by a murine macrophage cell line (RAW264.7). The cells were incubated with HA particles at various incubation time and phagocytosis was assessed using phagocytic index (PI). NO production from the culture supernatants was determined by the Griess reagent. The inducible nitric oxide synthase (iNOS) expression was determined by Western blot. The particles were also incubated with cells pretreated with various concentrations of L-N(6)-(1-iminoethyl) lysine hydrochloride (L-NIL) or L-arginine. Latex beads were used as a control. Our results showed that macrophage phagocytosis induced by HA was higher than that induced by the beads. However, NO production by HA-stimulated cells was lower than that by bead-stimulated cells. iNOS expression in both bead- and HA-stimulated cells was observed expressed at 7, 15, 30, and 60 min. l-Arginine enhanced but l-NIL inhibited both phagocytosis and NO production by HA-stimulated cells. The results of the present study suggest that nitric oxide may play a crucial role in HA-induced phagocytosis by RAW264.7 cells.
    Matched MeSH terms: Nitric Oxide/immunology*
  3. Mesaik MA, Khan KM, Rahim F, Taha M, Haider SM, Perveen S, et al.
    Bioorg Chem, 2015 Jun;60:118-22.
    PMID: 26000491 DOI: 10.1016/j.bioorg.2015.05.003
    The synthetic indole Mannich bases 1-13 have been investigated for their ability to modulate immune responses measured in vitro. These activities were based on monitoring their affects on T-lymphocyte proliferation, reactive oxygen species (ROS), IL (interleukin)-2, IL-4, and nitric oxide production. Compound 5 was found to be the most potent immunomodulator in this context. Four of the synthesized compounds, 5, 11, 12, and 13, have significant potent inhibitory effects on T-cell proliferation, IL-4, and nitric oxide production. However, none of the thirteen indole compounds exerted any activity against ROS production.
    Matched MeSH terms: Nitric Oxide/immunology
  4. Wan Osman WN, Che Ahmad Tantowi NA, Lau SF, Mohamed S
    J Food Biochem, 2019 03;43(3):e12755.
    PMID: 31353568 DOI: 10.1111/jfbc.12755
    The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia L. (MC) Noni leaves are non-toxic (unlike the fruits) and consumed as vegetables. The anti-osteoarthritis effects of the MC leaf extract against joint cartilage degradation and inflammation were investigated through cartilage explant cultures and pre-clinical animal study. Osteoarthritis were induced by intra-articular monosodium iodoacetate injection into the right knee. The extract, scopoletin and epicatechin, suppressed glycosaminoglycan and nitric oxide release from the cartilage explant in the presence of Interleukin-1β. After 28 days, the extract treatment reduced the in vivo serum levels and joint tissues mRNA expressions for joint cartilage degradation, aggrecanase, and collagenase biomarkers. The extract increased the bone formation marker PINP levels, besides improving the articular cartilage structure and chondrocytes cellularity. The extract improved bone formation/repair, subchondral bone structure, strength and integrity, as well as cartilage synthesis by suppressing inflammation, nitric oxide production, joint catabolism by proteases, and oxidative stress. PRACTICAL APPLICATIONS: The scopoletin (coumarin) and epicatechin (flavonoid) rich Morinda citrifolia (Noni) leaves may be used as vegetables, functional food ingredient, or dietary supplements to suppress osteoarthritis progression against joint cartilage degradation and inflammation. The extract, scopoletin, or epicatechin, suppressed glycosaminoglycan, and nitric oxide release from the cartilage. The Morinda citrifolia leaf extract suppressed inflammation, nitric oxide production, tissues catabolism by proteases and oxidative stress to help reduce joint cartilage degradation, besides improving the articular cartilage structure, chondrocytes health, subchondral bone structure, bone formation/repair, and cartilage synthesis.
    Matched MeSH terms: Nitric Oxide/immunology
  5. Chow YL, Lee KH, Vidyadaran S, Lajis NH, Akhtar MN, Israf DA, et al.
    Int Immunopharmacol, 2012 Apr;12(4):657-65.
    PMID: 22306767 DOI: 10.1016/j.intimp.2012.01.009
    The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs-associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-γ/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-α, IL-1β and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor-kappa B (NF-κB) signalling pathway via attenuation of NF-κB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders.
    Matched MeSH terms: Nitric Oxide/immunology
  6. Chien Yi K, Anna Pick Kiong L, Ying Pei W, Rhun Yian K, Sobri H
    J Tradit Chin Med, 2021 04;41(2):185-193.
    PMID: 33825397
    OBJECTIVE: To investigate the anti-neuroinflammatory properties of Panax ginseng (P. ginseng) root by measuring the levels of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-stimulated BV2 microglia cells.

    METHODS: Maximal non-toxic dose (MNTD) of methanol extract of P. ginseng root culture on BV2 microglia cells was first determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, followed by treatment and LPS stimulation of cells, and the measurement of NO using Griess assay and TNF-α, IL-6, and IL-10 using ELISA assay.

    RESULTS: The MNTD of P. ginseng root extract was determined to be (587 ± 57) µg/mL. Following that, NO and IL-6 levels were found to be insignificantly reduced by 6.88% and 0.14% respectively in stimulated cells upon treatment with MNTD. Treatment with MNTD yielded similar insignificant result, with only a reduction of 3.58% and 0.08% in NO and IL-6 levels respectively. However, TNF-α and IL-10 levels were significantly downregulated by 15.64% and 34.96% respectively upon treatment with P. ginseng root extract at MNTD.

    CONCLUSION: Methanol extract of P. ginseng root culture did not show any significant anti-inflammatory effects on NO and IL-6 levels, but might potentially possess both anti-neuroinflammatory and pro-neuroinflammatory properties through the downregulation of TNF-α and IL-10 respectively.

    Matched MeSH terms: Nitric Oxide/immunology
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