Nitric oxide production-IN-1

Nitric oxide production-IN-1 (Compound 1) is an inhibitor of nitric oxide (NO) production extracted from Tupistra chinensis. It effectively suppresses NO synthesis in rat abdominal macrophages upon stimulation with lipopolysaccharide [1].

1. Methyl eugenol (4-allylveratrole) is a natural constituent of the essential oils of a number of plants widely used in foodstuffs as flavouring agents, in view of the carcinogenic potential of ME, the need to check its presence in food products with effective analytical methods. 2. Methyleugenol has insecticidal properties. 3. Methyleugenol can inhibit the production of nitric oxide and decreased the protein expression of inducible nitric oxide synthase, it down-regulates the production of pro-inflammatory cytokines in the ischemic brain as well as in immunostimulated mixed glial cells; indicates that methyleugenol could be useful for the treatment of ischemia inflammation-related diseases. 4. Methyleugenol has cytotoxicity and genotoxicity. 5. Intravenous (i.v.) treatment with methyleugenol (ME) in either anesthetized or conscious rats elicits hypotension, an effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. 6. Methyleugenol has antinociceptive effect on the second phase of formalin-induced pain, may be due to the inhibition of N-methyl-d-aspartic acid (NMDA) receptor-mediated hyperalgesia via GABA(A) receptors. 7. Methyleugenol has elaxant and antispasmodic actions on guinea-pig isolated ileum.

Anhydronotoptol (4-{[(2E,5E)-3,7-dimethylocta-2,5,7-trien-1-yl]oxy}-7H-furo[3,2-g]chromen-7-one), a natural compound extracted from the umbelliferae plant Qiangwu, is a potent inhibitor of nitric oxide production, inhibiting LPS-induced NO production in RAW 264.7 cells with an IC50 value of 36.6 μM.

PDE1-IN-9 (Compound 7a) is a selective inhibitor of phosphodiesterase 1 (PDE1), targeting PDE1C with an IC50 value of 11 nM. It effectively reduces the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS, while also inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS). Additionally, PDE1-IN-9 demonstrates good metabolic stability in rat liver microsomes.

T-5342126 is a toll-like receptor 4 (TLR4) antagonist that reduces LPS-induced production of nitric oxide (NO) in RAW 264.7 cells (IC50 = 27.8 μM) and decreases LPS-induced IL-8, TNF-α, and IL-6 production in isolated human whole blood (IC50s = 110.5, 315.6, and 318.4 μM, respectively). T-5342126 (82 mg kg) also reduces ethanol intake and the abundance of ionized calcium-binding adapter molecule 1 (Iba1), a marker of microglial activation, in the central nucleus of the amygdala in ethanol-dependent mice.

AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg kg) decreases MPTP-induced increases in lipid peroxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson's disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)

Nargenicin is a macrolide antibiotic that selectively inhibits the growth of S. aureus, methicilin resistant S. aureus (MRSA), and M. luteus (MICs = 0.6, 0.3, and 2.5 μg/ml, respectively) over a panel of 11 Gram-positive and Gram-negative bacteria (MICs = >80 μg/ml). [1] It dose-dependently inhibits S. aureus DnaE in the presence of DNase I-activated DNA and E. coli DnaE when used at concentrations of 0.00001-0.1 and 0.01-100 μg/mL, respectively. [2] In murine BV-2 microglial cells, nargenicin (1 μM) inhibits cytokine expression and nitric oxide production induced by LPS.[3] Nargenicin (200 μM), when used in combination with 1,25-dihydroxyvitamin D3 or all-trans retinoic acid , reduces cell proliferation by 37-47% and increases cell differentiation by 82-85% in HL-60 human myeloid leukemia cells.[4]

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

L-Sepiapterin, also known as Sepiapterin, is a precursor compound crucial for the production of tetrahydrobiopterin (BH4), which serves as a coenzyme for endothelial nitric oxide synthase (eNOS). This compound demonstrates its efficacy by improving endothelial dysfunction in small mesenteric arteries from db db mice and promoting angiogenesis. Moreover, L-Sepiapterin exerts inhibitory effects on cellular proliferation and migration in ovarian cancer cells through the down-regulation of p70S6K-dependent vascular endothelial growth factor receptor-2 (VEGFR-2) expression[1][2].

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

1. Sesamolin and Sesamin has neuroprotective effect. 2. Sesamolin protects microglia against H2O2-induced cell injury, by inhibiting of p38 MAPK and caspase-3 activation and ROS production. 3. Sesamolin and Sesamin can significantly attenuate the excess g

ABAI-30 is a highly potent and orally bioavailable anti-inflammatory compound that efficiently suppresses nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW264.7 cells [1].

COX-2-IN-16 (compound 2b) is a potent, selective, and orally active inhibitor of cyclooxygenase-2 (COX-2) with an IC50 value of 102 μM, effectively reducing nitric oxide (NO) production and demonstrating anti-inflammatory activity [1].

Akt NF-κB JNK-IN-1 (Compound 2i) is an inhibitor of the Akt, NF-κB, and JNK signaling pathways, demonstrating inhibition of nitric oxide production (IC50: 3.15 μM) and exhibiting anti-inflammatory effects.

α7 nAchR-JAK2-STAT3 agonist 1 is a potent inhibitor of the α7 nAchR-JAK2-STAT3 pathway that acts on nitric oxide (NO) (IC50: 0.32 μM). It has demonstrated positive effects on iNOS, IL-1β, and IL-1β in murine macrophages RAW264.7, and inhibited the expression of iNOS, IL-1β, and IL-6 in mouse macrophages. Additionally, α7 nAchR-JAK2-STAT3 agonist 1 suppressed LPS-induced NO release, NF-κB activation, and cytokine production, making it useful for studying sepsis.

1. Ginsenoside Rg5 could be a beneficial agent for the treatment of Alzheimer's disease. 2. Ginsenoside Rg5 suppresses LPS-induced nitric oxide (NO) production and proinflammatory TNF-α secretion. 3. Ginsenoside Rg5 can ameliorate lung inflammation possib

1. Irisflorentin blocks apoptosis pathways, by exerting its effects by promoting rpn-3 expression to enhance the activity of proteasomes and down-regulating egl-1 expression. 2. Irisflorentin has anti-inflammatory mechanism in LPS-activated RAW 264.7 macr

Lornoxicam-d4 is intended for use as an internal standard for the quantification of lornoxicam by GC- or LC-MS. Lornoxicam is a COX inhibitor and non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. It inhibits production of thromboxane B2 from arachidonic acid in HEL human erythroleukemic cells, which endogenously express COX-1, as well as inhibits LPS-induced formation of prostaglandin F1α from arachidonic acid in Mono-Mac-6 cells, which endogenously express COX-2. Lornoxicam reduces LPS-induced production of nitric oxide and IL-6 in cell-based assays with IC50 values of 65 and 54 µM, respectively. It reduces carrageenan-induced paw edema in rats when administered intravenously at doses ranging from 0.1 to 9 mg kg. Formulations containing lornoxicam have been used in the management of postoperative pain.

Keap1-Nrf2-IN-11 (Compound 6k), a potent Keap1-Nrf2 inhibitor, exhibits a dissociation constant (KD) of 0.21 nM. It hampers the production of reactive oxygen species (ROS) and nitric oxide (NO), as well as the expression of tumor necrosis factor-alpha (TNF-α). By promoting Nrf2 nuclear translocation, it mitigates inflammation and is utilized in anti-inflammatory studies [1].

Aminoguanidine hemisulfate, an inhibitor of nitric oxide synthases (NOS) and reactive oxygen species (ROS), effectively suppresses ANE-induced ROS production in vitro and is utilized in cancer research [1].

Semapimod is an inhibitor of proinflammatory cytokine production, capable of suppressing TNF-α, IL-1β, and IL-6. It hinders TLR4 signaling with an IC50 of approximately 0.3 μM, impedes p38 MAPK, and reduces nitric oxide production in macrophages. This compound shows promise for treating various inflammatory and autoimmune disorders [1] [2] [3].

HDAC-IN-62 (Compound 5), an HDAC inhibitor, exhibits IC50 values of 0.78, 1.0, and 1.2 μM for HDAC6, HDAC8, and HDAC11, respectively. This compound suppresses microglial activation via autophagy induction and reduces nitric oxide production, demonstrating anti-inflammatory and antidepressant properties. Additionally, HDAC-IN-62 has been shown to inhibit microglial activation in mouse brains [1].

Compound 2v (Anti-inflammatory agent 45) demonstrates anticancer properties with direct inhibitory impacts on the proliferation of various blood malignancies, such as leukemia, lymphoma, and myeloma cell lines. It induces apoptosis and suppresses nitric oxide production in HL60 leukemia cells (IC50 = 14.7 μM) [1].

Anti-inflammatory agent 54 (compound 9c), a Coixol derivative, exhibits anti-inflammatory properties by inhibiting the NF-κB pathway and reducing the expression of pro-inflammatory cytokines such as iNOS, TNF-α, IL-6, and IL-1β. It effectively suppresses LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with an IC50 of 2.4 μM and demonstrates in vivo efficacy in a mouse auricular edema model [1].